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Molecular Pathogens 2025, Vol.16, No.1 http://microbescipublisher.com/index.php/mp © 2025 MicroSci Publisher, an online publishing platform of Sophia Publishing Group. All Rights Reserved. Sophia Publishing Group (SPG), founded in British Columbia of Canada, is a multilingual publisher. Publisher MicroSci Publisher Editedby Editorial Team of Molecular Pathogens Email: edit@mp.microbescipublisher.com Website: http://microbescipublisher.com/index.php/mp Address: 11388 Stevenston Hwy, PO Box 96016, Richmond, V7A 5J5, British Columbia Canada Molecular Pathogens (ISSN 1925-1998) is an open access, peer reviewed journal published online by MicroSciPublisher. The journal is committed to publishing and disseminating all the latest and outstanding research articles, letters and reviews in all areas of molecular pathogens. The range of topics including isolation and identification of emerging pathogens viruses, pathogen-host interactions, genetics and evolution, genomics and gene regulation, proteomics and signal transduction, glycomics and signal recognition, virulence factors and vaccine design and other topical advisory subjects. All the articles published in Molecular Pathogens are Open Access, and are distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. MicroSci Publisher uses CrossCheck service to identify academic plagiarism through the world’s leading plagiarism prevention tool, iParadigms, and to protect the original authors’ copyrights. MicroSci Publisher is an international Open Access publisher specializing in microbiology, bacteriology, mycology, molecular and cellular biology and virology registered at the publishing platform that is operated by Sophia Publishing Group (SPG), founded in British Columbia of Canada.
Molecular Pathogens (online), 2025, Vol. 16, No. 1 ISSN 1925-1998 http://microbescipublisher.com/index.php/mp © 2025 MicroSci Publisher, an online publishing platform of Sophia Publishing Group. All Rights Reserved. Sophia Publishing Group (SPG), founded in British Columbia of Canada, is a multilingual publisher. Latest Content Host-Pathogen Interactions in Water Buffalo: Insights from Immune Response Studies Hui Liu Molecular Pathogens, 2025, Vol. 16, No. 1, 1-9 Case Study: Enhancing Cotton’s Resistance to Fungal Pathogens Pingping Yang, Jin Zhang Molecular Pathogens, 2025, Vol. 16, No. 1, 10-18 Role of Microbiomes in Wheat Disease Suppression Xiaoqing Tang Molecular Pathogens, 2025, Vol. 16, No. 1, 19-26 Meta-Analysis of Disease Resistance Genes in Sweet Potato: A Focus on Viral and Fungal Pathogens Jianquan Li Molecular Pathogens, 2025, Vol. 16, No. 1, 27-35 Breeding Disease-Resistant Potatoes through Molecular Tools Lin Liu, Fumin Gao Molecular Pathogens, 2025, Vol. 16, No. 1, 36-44
Molecular Pathogens, 2025, Vol.16, No.1, 1-9 http://microbescipublisher.com/index.php/mp 1 Research Insight Open Access Host-Pathogen Interactions in Water Buffalo: Insights from Immune Response Studies Hui Liu Research Center, Hainan Institute of Tropical Agricultural Resources, Sanya, 572025, Hainan, China Corresponding email: hui.liu@hitar.org Molecular Pathogens, 2025, Vol.16, No.1 doi: 10.5376/mp.2025.16.0001 Received: 04 Nov., 2024 Accepted: 20 Dec., 2024 Published: 05 Jan., 2025 Copyright © 2025 Liu, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Lui H., 2025, Mechanisms of immune evasion by african swine fever virus: an integrated review, Molecular Pathogens, 16(1): 1-9 (doi: 10.5376/mp.2025.16.0001) Abstract This study reviews the main components of the innate and adaptive immune systems in water buffalo, focusing on immune response mechanisms in common diseases such as brucellosis, foot-and-mouth disease, and trypanosomiasis. It analyzes the critical roles of Toll-like receptors (TLRs), cytokines, and major histocompatibility complex (MHC) in pathogen recognition and immune activation. Case studies further illustrate the application of genomics and proteomics in the study of disease resistance in water buffalo, highlighting the potential of selective breeding and vaccine development to enhance disease resistance. Through a systematic analysis of host-pathogen interaction mechanisms in water buffalo, this study aims to reveal how pathogens influence host responses through immune evasion strategies, providing insights for breeding improvement and vaccine development. Keywords Water buffalo; Immune response; Brucellosis; Foot-and-mouth disease; Selective breeding 1 Introduction Bubalus bubalis plays an important role in agriculture in many countries, especially in Asia and South America. They are mainly used to produce milk and meat, and are often used to cultivate the land. For example, in India, water buffalo are the main dairy-producing animals and have made great contributions to the dairy industry (Dubey, 2018). Water buffalo adapt to tropical and subtropical environments, which makes them particularly useful in places like flood-prone or harsh environments (Martínez-Burnes et al., 2024). Nowadays, people are in a growing demand for buffalo products, and therefore they are more concerned about how to increase their output, which shows that they are of great economic value (Ciuca et al., 2020). However, water buffalo are prone to infection with various pathogens. These pathogens can affect their health and also reduce their yields. Some viral diseases, such as foot-and-mouth disease, rinderpest and viral diarrhea of bovine can not only infect water buffalo, but also infect scalpers. These diseases are contagious and are threatening to both animal and human health. Water buffalo are also prone to parasitic infections, such as Neospora and Toxoplasma. These parasites can cause abortion or embryonic death, leading to economic losses (Kengradomkij et al., 2015). There are also some protozoa parasites, such as Babes and Taylor, that also infect water buffalo. Although water buffalo are usually milder than scalpers (Silveira et al., 2016; Benítez et al., 2018), the presence of these pathogens suggests that we need to continue to pay attention to them, study and monitor them in order to find good prevention and control methods. This article will systematically talk about how water buffalo and pathogens interact, focusing on new advances in vaccines and immunotherapy. We will also look at the genetic and environmental factors that affect buffalo's disease resistance, hoping to improve buffalo's health and yield through targeted measures, thereby helping farmers and agricultural economies that rely on buffalo. 2 Pathogens and Diseases Impacting Water Buffalo 2.1 Bacterial pathogens A bacteria called Brucella abortus can cause buffalo brucella. This disease can also be transmitted to people, and it will affect buffalo reproduction and cause economic losses. Studies have found that water buffalo can react
Molecular Pathogens, 2025, Vol.16, No.1, 1-9 http://microbescipublisher.com/index.php/mp 2 immune to the bacteria. Even if the vaccine dose is reduced, the immunity effect produced by buffalo is similar to the standard dose (Shome et al., 2020). This is helpful for getting more buffalo vaccinated. When water buffalo get brucellosis, the lymphocytes in the body will change. These changes can be detected using a method called flow cytometry, which is useful for diagnosis (Grandoni et al., 2023). In addition, the study also found that some special miRNAs can also appear in the buffalo's blood during infection, which may become a new method to detect the condition without surgery. There is also a bacteria called Mycobacterium bovine, which can cause bovine tuberculosis and can also infect water buffalo. Special antibodies will be produced after buffalo infection, and blood tests can now detect these antibodies. However, detection methods need to be adjusted according to different animals (Lyashchenko et al., 2020). In addition, there is a method called the interferon-γ release test, which can also be used to detect whether buffalo is infected with this bacteria (Smith et al., 2020). Researchers are also trying to find some new immune signaling substances to improve the accuracy of the detection. 2.2 Viral pathogens Buffalopox is a viral disease that can make buffalo sick and may also affect their yields. There are not many studies on buffalopox, but this disease still needs to be paid attention to, especially in buffalo health management. Foot-and-mouth disease is a highly contagious viral disease. Not only water buffalo, but many livestock can be infected. After buffalo is infected, sometimes there will be no obvious symptoms, but it may still be transmitted to other animals. Therefore, buffalo is an important factor in the prevention and control of foot-and-mouth disease. Studies have found that the antibody response of buffalo after being vaccinated is similar to that of cows. There is now a detection method called Affinity ELISA that can be used to detect vaccine effects, which is as reliable as traditional methods (Sala et al., 2023). 2.3 Parasitic infections Water buffalo can also be infected by some parasites. For example, trypanosomiasis-also known as surra-is a disease transmitted by blood-sucking insects like horseflies. After infection, water buffalo may become anemia, swelling, thinner, and in severe cases, neurological problems and even death. This disease can be detected by microscope to find parasites or by PCR. Control measures include insect extermination, vaccination and medication. Liver tablet flukesomiasis is another parasitic disease, mainly caused by a bug called “Huge Piece Twinksomiasis”. If buffalo drinks contaminated water or eats plants with insect eggs, they may be infected. The insects can enter the liver, causing liver damage, causing the buffalo to grow slowly and produce less milk. If the disease lasts for a long time, it may cause cirrhosis and even liver failure (Figure 1) (Shi et al., 2017). This disease can be diagnosed by checking feces or having blood tests. Prevention and control methods include deworming water buffalo, managing pastures well, and controlling intermediate hosts such as snails to cut off the transmission chain of parasites. 3 Immune System of Water Buffalo 3.1 Key components of the innate immune system The buffalo’s body can recognize bacteria on its own and respond quickly, which is their innate immunity. They have many “sensors” in their bodies, such as structures called NOD-like receptors (NLRs). These receptors can discover the components of bacteria and trigger an immune response. They are found in many animals and have similar structures. NLR uses signaling pathways such as NF-κB to cause the body to produce an inflammatory response, thereby fighting bacteria. There are also some “immune soldiers” in the buffalo’s body, such as macrophages and dendritic cells. These cells can present the "look" of pathogens and remind T cells to initiate a stronger immune response. T cells are very important in the body’s fight against bacteria (Jo, 2019). 3.2 Adaptive immune responses-role of t and b lymphocytes Water buffalo not only have innate immunity, but also have a system called “adaptive immunity”. This is mainly done by T cells and B cells. They can identify specific bacteria and cause more accurate responses. Studies have found that when water buffalo are infected with Brucella, the number of T and B cells in their bodies decreases. This shows that these cells are useful in fighting bacteria (Jiang, 2024). T cells can also release a substance called IFN-γ, which can activate macrophages and clear the bacteria into a cleaner (Shome et al., 2020).
Molecular Pathogens, 2025, Vol.16, No.1, 1-9 http://microbescipublisher.com/index.php/mp 3 Figure 1 Histopathological characteristics of the livers of water buffalo infected with Fasciola gigantica (Adopted from Shi et al., 2017) Image caption: a: At 3 dpi, there was local hyperemia associated with mild filtration of lymphocytes and neutrophils. b: At 10 dpi, there was scattered vacuolation of hepatocytes, consistent with fat, along with mild to moderate focal necrosis. c: At 28 dpi, diffuse intravascular coagulation, severe infiltration of inflammatory cells mainly neutrophils and lymphocytes, and granular degeneration of the cytoplasm were observed. d: At 42 dpi, moderate to severe multifocal hemorrhages and necrosis, infiltration of eosinophils, RBCs and monocytes, and accumulation of fibroblasts were detected. e: At 70 dpi, there were mild to moderate multifocal bile duct hyperplasia and focal coagulative necrosis associated with collagen deposition. f: At 98 dpi, severe periportal fibrosis associated with multifocal inflammatory infiltrate, cellular debris, moderate multifocal hemorrhages, and granulomas with necrotic centres were detected. g: Liver tissue from uninfected animal showed normal histological architecture of the hepatic tissue. h: Adult flukes in the intrahepatic bile duct, along with epithelial hyperplasia of the duct. In all figures, tissue sections were stained with H&E and arrows point at the corresponding morphological features described above. Scale-bars: a-g, 50 μm; h, 100 μm (Adopted from Shi et al., 2017) 3.3 Comparative immunology-differences between water buffalo and other livestock 3.3.1 Genetic diversity in immune genes The water buffalo has many types of immune genes, which also makes their immune responses different from those of other animals. For example, although the NOD1 and NOD2 genes in their bodies are similar to those in other mammals, they also have some differences, which may affect their immune effects (Brahma et al., 2015). 3.3.2 Species-specific immune adaptations Water buffalo responds to some diseases lighter than other animals. For example, when they are infected with bovine babesworms, their symptoms are usually not serious. This may be because their innate immune system responds faster, which can reduce the number of parasites in the body and reduce symptoms (Benítez et al., 2018). This may be because the immune signaling pathways in their bodies are regulated in different ways. 3.3.3 Implications for disease susceptibility and resistance The immune characteristics of water buffalo will directly affect their resistance to some diseases. For example,
Molecular Pathogens, 2025, Vol.16, No.1, 1-9 http://microbescipublisher.com/index.php/mp 4 their response to Brucella and Tremocostus is quite special and will produce different immune substances and signals. It is precisely because of these differences that they show different resistance when facing certain diseases (Zhang et al., 2017; Grandoni et al., 2023). 4 Mechanisms of Host-Pathogen Interactions 4.1 Pathogen recognition and immune activation When water buffalo are infected with parasites like giant hepatic flukesomiae, schistosomiae, their immune systems begin to work. The “front line defense” in the buffalo’s body-the innate immune system, will first recognize the pathogen. They discover these invaders by identifying special molecules called “PAMPs” (Mabbott, 2018). These molecules are usually only found in pathogens such as bacteria and parasites. During infection, water buffalo produce special “signal molecules” such as IFN-γ, IL-4 and IL-10. These substances can make the immune system more active or converge, helping the body regulate the intensity of the response. If it is infected with giant hepatic flukes, these molecules will change differently at different times, indicating that the body has been working hard to deal with the pathogen. After infection with Schistosoma japanese, specific antibodies to the larval stage will be quickly produced in the buffalo, indicating that their immune system can recognize and respond in a timely manner. 4.2 Evasion strategies employed by pathogens However, not all pathogens will be easily defeated. Some parasites like giant tidalis are smart, and they learn to “pretend to be stupid” or “hide” to escape the buffalo’s immune system. At the beginning, water buffalo will develop an immune response to these bugs called Th2, a common way to fight parasites. But this reaction will soon be “suppressed” by the parasite, making the immune system less intense. This is because parasites reduce pro-inflammatory molecules and make the body more “tolerant” so that they can stay in the body for a long time without being removed (Zhang et al., 2017). There are similar ways to escape from schistosomiae. They bind to some antibodies in the buffalo, so that they can "disguise" themselves and are not easily seen by immune cells (Hosking et al., 2015). These clever strategies allow pathogens to survive in water buffalo for a long time. 4.3 Immune signaling pathways and cytokine responses When water buffalo are infected with pathogens, there are many changes in the immune signal in the body. These changes are accomplished through different cytokines. For example, when infected with giant tidalis, the buffalo’s body will show an inhibitory reaction at the beginning, and the level of TGF-β will increase, which is actually helping the parasite to “set up” better. Gradually, the buffalo's immune response will become a “mixed type”, that is, both Th1 and Th2 types of reactions. Later, the reaction tends toward Th1 and Treg, which makes the infection persistent (Shi et al., 2017). When infected with giant hepatic flukes, whether it is the first infection or the second infection, the buffalo’s Th2 reaction is very strong, while the Th1 type has almost no changes. This shows that the buffalo’s immune system has a relatively stable response pattern to this pathogen (Meng et al., 2023). These reaction patterns help us better understand how buffalo deals with pathogens, and also provide direction for the future development of treatment and prevention and control methods. 5 Genetic and Molecular Insights into Immune Response 5.1 Identification of immune-related genes and markers Scientists have found many genes and markers related to buffalo immunity. These genes play a key role in buffalo's resistance to bacteria and parasites. For example, when water buffalo are infected with giant hepatic flukes, the activity of some genes responsible for immunity (such as cytokines and transcription factors) in the body changes. This suggests that they have an effect on immune response (Shi et al., 2017; Wang, 2024). In addition, during the study of buffalo infection with circular Taylorworm, the performance of genes such as MHC (main histocompatibility complex) and TLR (Toll-like receptor) were also examined. However, these genes did not change significantly in that infection, which may indicate that they have little effect on combating this pathogen. Through genome comparison, the study also found that NOD-like receptors (NLRs) in water buffalo are very important for identifying bacteria. They can detect bacteria at the first time and initiate an immune response (Brahma et al., 2015).
Molecular Pathogens, 2025, Vol.16, No.1, 1-9 http://microbescipublisher.com/index.php/mp 5 5.2 Role of toll-like receptors (TLRs) in pathogen recognition TLRs are a special class of receptors that can recognize pathogens such as viruses, bacteria and other pathogens and are the “radars” of the immune system. In buffalo, TLRs can detect various pathogens, such as avian influenza viruses. These receptors also work with other immune signaling pathways (like RIG-I-like receptors). The genes of these receptors show a lot of changes in water buffalo, which means they may have adapted to invasions of different viruses or bacteria (Jax et al., 2022). Although there are not many studies on buffalo TLRs at present, we already know that they play a big role in initiating immune responses (Panigrahia et al., 2016). 5.3 Transcriptomic and proteomic analysis of infected tissues By analyzing gene expression (transcriptionome) and protein changes (proteome) in the tissues after buffalo infection, we can have a clearer understanding of what is happening in their bodies. For example, when water buffalo were infected with giant hepatic flukes, transcriptome studies found that the expression of many cytokines and transcription factors would change at different time points. These changes are related to liver lesion processes and regulation of immune responses. The proteome study also found that some of the proteins released by the parasite interact with the substances in the buffalo’s blood. These proteins may help parasites escape the immune system or interfere with the buffalo’s defense mechanisms (Huang et al., 2019). These studies illustrate the complexity of the buffalo immune response, and also allow us to see new therapeutic directions, such as finding some proteins as drug targets to help water buffalo better fight infections. 6 Environmental and Management Factors Influencing Disease Susceptibility 6.1 Effects of nutrition and stress on immune competence The immunity of water buffalo has a lot to do with whether they eat well and whether they are often stimulated. If water buffalo cannot keep up with their nutrition, their bodies will be prone to problems and their chances of getting sick are higher. Eating well can sometimes make the immune system stronger, and may also make pathogens “eat well” and live longer (Pike et al., 2019). Various stresses can also affect the immune response. Some are caused by nature, such as temperature changes; some are artificial, such as crowding, transportation, water shortage, etc. For example, if water buffalo do not eat enough, they will not be able to reproduce well and the bacteria will not survive long; but environmental pressures like high temperatures will weaken the water buffalo, which will make the bacteria more likely to spread (Vicente-Santos et al., 2023). In some African buffalo studies, it was found that if the nutrition is insufficient and infected with a variety of parasites, the health of the buffalo will be worse. Especially parasites like Schistosoma, they are particularly easy to take advantage of the situation. This also shows that nutrition and immunity are indeed closely related. 6.2 Influence of climate and habitat on disease dynamics The environment in which buffalo lives and the changes in weather will also affect whether they are prone to illness. Environments such as temperature, humidity, and whether living places are clean, will affect the microorganisms in the water buffalo's body, which are important to the immune system (Bernardo-Cravo et al., 2020). Some studies have found that water buffalo are more likely to be infected with parasites when seasons change, such as from dry season to rainy season. Some terrain, such as by ponds or near wetlands, are “hot spots” where pathogens are particularly prone to spread (Beechler et al., 2017). The microorganisms in animals' bodies will also change due to changes in the environment, which will affect immunity and infection. Just like amphibians, once the temperature changes, infections can become more complex and the immune system may become weaker (Herczeg et al., 2021). 6.3 Impact of veterinary interventions and vaccination programs Vaccinating water buffalo or treating them in time can indeed reduce many diseases. For example, studies have found that treatment with praziquantel can significantly reduce the number of eggs and insects caused by schistosomiasis in Japan. This treatment can also help water buffalo become more resistant the next time they encounter infection (He et al., 2018). However, the problem is not that simple. If the buffalo is infected with other bacteria at the same time, their response to the new vaccine may not be very good, and their immunity will be
Molecular Pathogens, 2025, Vol.16, No.1, 1-9 http://microbescipublisher.com/index.php/mp 6 disturbed. To solve this problem, we need to understand more about their immune responses in the body when they are infected, such as how cytokines change. This information can help us design more effective vaccines and treatments (Meng et al., 2023). 7 Case Studies of Immune Response to Specific Pathogens 7.1 Brucellosis: immune mechanisms and control measures Brucellosis is a relatively big problem for water buffalo. This disease not only affects the health of water buffalo, but also reduces milk production and fertility. The immune response of buffalo to Brucella is divided into two parts: innate immunity and adaptive immunity. Innate immunity is the body's first line of defense. Some “immune sensors” like NOD-like receptors will discover bacterial components and then initiate an immune response. These receptors trigger a process that allows the body to produce some pro-inflammatory cytokines, which help fight bacterial infections (Brahma et al., 2015). In order to prevent buffalo from being infected with Brucella, the main method is to vaccinate them, and to do a good job in epidemic prevention, such as isolating sick cattle, cleaning the environment, etc., to reduce the chance of virus transmission. 7.2 Foot-and-mouth disease: vaccine development and host immunity Foot-and-mouth disease is a highly contagious disease and is also a major threat to the buffalo group. Therefore, it is very important to develop effective vaccines. To make the vaccine work better, researchers hope it can inspire a strong immune response, including allowing the body to produce antibodies (humoral immunity) and active immune cells (cellular immunity). When first infected, the buffalo's immune system will first use receptors such as NOD1 and NOD2 to recognize the virus. These receptors can activate immune signaling pathways and produce inflammatory responses. In the laboratory, scientists used buffalo immune cells, such as monocytes (PBMCs), macrophages and breast cells in the blood. It was found that after stimulating these cells with NOD receptor agonists, a large number of IFN-γ and proinflammatory factors were produced, indicating that the immune response was successfully initiated (Figure 2) (Brahma et al., 2015). Understanding these mechanisms will help us design stronger and longer-acting vaccines. Figure 2 Comparison of LRR domains of buNOD1 (left panel) and buNOD2 (right panel) (Adopted from Brahma et al., 2015)
Molecular Pathogens, 2025, Vol.16, No.1, 1-9 http://microbescipublisher.com/index.php/mp 7 7.3 Trypanosomiasis: host resistance and disease persistence Trypanosomavirus is caused by a parasite called Trypanosoma. The trouble with this disease is that it is not easy to cure completely and will become a chronic disease. The immune response in the buffalo body includes both pro-inflammatory factors and anti-inflammatory factors, and the two need to be balanced. Studies have found that some water buffalo can control the number of parasites in their bodies through a strong innate immune response, and can also reduce the severity of the disease. For example, they show relatively strong immunity to parasites like the bobbabesworm (Benítez et al., 2018). This shows that although trypanosomiasis is easy to become chronic, some immune mechanisms in water buffalo may also help them better fight the invasion of trypanosomia. 8 Applications in Disease Control and Breeding Programs 8.1 Selective breeding for disease resistance Improving water buffalo's disease resistance through breeding is an increasingly optimistic approach. Studies have found that changes in some genes, such as a site called g.4002C>T in the interleukin 10 gene, will affect whether water buffalo are prone to bovine tuberculosis (bTB). water buffalo with a certain genotype (such as CC type) are less likely to get this disease than individuals with TT type. This suggests that these genes can be used as markers to select healthier water buffalo (Iannaccone et al., 2019). Some people have also studied genes related to mastitis, which can affect milk production. Researchers have found many genetic mutations, which can be used as reference targets in future breeding (Jaiswal et al., 2021), thereby selecting water buffalo that are not prone to mastitis. 8.2 Development of immunomodulatory vaccines To control the infectious diseases of buffalo, we also need vaccines that can regulate the immune response. Some studies have pointed out that if a buffalo is infected with schistosomiasis once, it may develop immunity next time, which means that the buffalo's immune system remembers this enemy. This finding is helpful in designing new vaccines (He et al., 2018). There is currently a BoHV-1 gE deletion vaccine, and studies have shown that it can stimulate the buffalo's antibody response to the herpes virus. However, the protective effect of this vaccine needs to be confirmed more research (Martucciello et al., 2023). These studies show that we have the opportunity to develop vaccines that can not only activate the buffalo's natural immune system but also enhance acquired immunity. 8.3 Use of probiotics and immunostimulants in disease prevention In addition to vaccines, probiotics and immune enhancers can also help buffalo fight disease. These substances can enhance the innate immunity of water buffalo and allow the body to recognize and remove bacteria faster. There are some natural antibacterial substances in the buffalo, such as defensins and antibacterial peptides (AMP). They can directly kill germs and regulate the immune system's response (Chanu et al., 2018). The study also found that the number and activity of these antimicrobial peptides can be "stimulated" by some external factors, which means that we have ways to make the buffalo's immunity stronger. Therefore, combining probiotics, immune enhancers and vaccines can make the buffalo's overall disease prevention ability more stable and powerful. Acknowledgments Thanks Dr. Q. Wang from the Hainan Institution of Biotechnology for his assistance with the serious reading and helpful discussions during the course of this work. Conflict of Interest Disclosure The author affirms that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. References Beechler B.R., Jolles A.E., Budischak S.A., Corstjens P.L.A.M., Ezenwa V.O., Smith M., Spaan R., Van Dam G., and Steinauer M., 2017, Host immunity nutrition and coinfection alter longitudinal infection patterns of schistosomes in a free ranging African buffalo population, PLoS Neglected Tropical Diseases, 11(12): e0006122. https://doi.org/10.1371/journal.pntd.0006122
Molecular Pathogens, 2025, Vol.16, No.1, 1-9 http://microbescipublisher.com/index.php/mp 8 Benítez D., Mesplet M., Echaide I., De Echaide S., Schnittger L., and Florin-Christensen M., 2018, Mitigated clinical disease in water buffalo experimentally infected with Babesia bovis, Ticks and Tick-Borne Diseases, 9(5): 1358-1363. https://doi.org/10.1016/j.ttbdis.2018.04.012 Bernardo-Cravo A.P., Schmeller D.S., Chatzinotas A., Vredenburg V.T., and Loyau A., 2020, Environmental factors and host microbiomes shape host-pathogen dynamics, Trends in Parasitology, 36(7): 616-633. https://doi.org/10.1016/j.pt.2020.04.010 Brahma B., Kumar S., De B.C., Mishra P., Patra M.C., Gaur D., Chopra M., Gautam D., Mahanty S., Malik H., Malakar D., Datta T., and De S., 2015, Comparative genomic analysis of buffalo (Bubalus bubalis) NOD1 and NOD2 receptors and their functional role in in-vitro cellular immune response, PLoS One, 10(3): e0119178. https://doi.org/10.1371/journal.pone.0119178 Chanu K.V., Thakuria D., and Kumar S., 2018, Antimicrobial peptides of buffalo and their role in host defenses, Veterinary World, 11(2): 192. https://doi.org/10.14202/vetworld.2018.192-200 Ciuca L., Borriello G., Bosco A., D’Andrea L., Cringoli G., Ciaramella P., Maurelli M., Di Loria A., Rinaldi L., and Guccione J., 2020, Seroprevalence and clinical outcomes of Neospora caninum, Toxoplasma gondii and Besnoitia besnoiti infections in water buffalo (Bubalus bubalis), Animals, 10(3): 532. https://doi.org/10.3390/ani10030532 Dubey J.D., 2018, A review of coccidiosis in water buffalo (Bubalus bubalis), Veterinary Parasitology, 256: 50-57. https://doi.org/10.1016/j.vetpar.2018.04.005 Grandoni F., Signorelli F., Martucciello A., Napolitano F., De Donato I., Donniacuo A., Di Vuolo G., De Matteis G., Del Zotto G., Davis W., and De Carlo E., 2023, In‐depth immunophenotyping reveals significant alteration of lymphocytes in buffalo with brucellosis, Cytometry Part A, 103(6): 528-536. https://doi.org/10.1002/cyto.a.24710 He C.C., Mao Y.D., Zhang X., Li H., Lu K., Fu Z.Q., Hong Y., Tang Y.L., Jin Y.M., Lin J.J., and Liu J.M., 2018, High resistance of water buffalo against reinfection with Schistosoma japonicum, Veterinary Parasitology, 261: 18-21. https://doi.org/10.1016/j.vetpar.2018.08.001 Herczeg D., Ujszegi J., Kásler A., Holly D., and Hettyey A., 2021, Host–multiparasite interactions in amphibians: a review, Parasites and Vectors, 14(1): 296. https://doi.org/10.1186/s13071-021-04796-1 Hosking C., Driguez P., McWilliam H., Ilag L., Gladman S., Li Y., Piedrafita D., McManus D., Meeusen E., and De Veer M., 2015, Using the local immune response from the natural buffalo host to generate an antibody fragment library that binds the early larval stages of Schistosoma japonicum, International Journal for Parasitology, 45(11): 729-740. https://doi.org/10.1016/j.ijpara.2015.05.002 Huang S.Y., Yue D.M., Hou J.L., Zhang X.X., Zhang F., Wang C., and Zhu X., 2019, Proteomic analysis of Fasciola gigantica excretory and secretory products (FgESPs) interacting with buffalo serum of different infection periods by shotgun LC-MS/MS, Parasitology Research, 118: 453-460. https://doi.org/10.1007/s00436-018-6169-z Iannaccone M., Cosenza G., Pauciullo A., Martino C., Ianni A., Capparelli R., and Martino G., 2019, Water buffalo (Bubalus bubalis) susceptibility to bovine tuberculosis is influenced by g.4002c>t polymorphism in interleukin-10 gene, Buffalo Bulletin, 38(1): 135-139. Jaiswal S., Jagannadham J., Kumari J., Iquebal M.A., Gurjar A., Nayan V., Angadi U.B., Kumar S., Kumar R., Datta T., Rai A., and Kumar D., 2021, Genome wide prediction mapping and development of genomic resources of mastitis associated genes in water buffalo, Frontiers in Veterinary Science, 8: 593871. https://doi.org/10.3389/fvets.2021.593871 Jax E., Franchini P., Sekar V., Ottenburghs J., Parera D., Kellenberger R., Magor K., Müller I., Wikelski M., and Kraus R., 2022, Comparative genomics of the waterfowl innate immune system, Molecular Biology and Evolution, 39(8): msac160. https://doi.org/10.1093/molbev/msac160 Jiang F., 2024, Investigation on the differentiation and functions of immunological memory cells, Journal of Vaccine Research, 14(1): 31-38. https://doi.org/10.5376/jvr.2024.14.0005 Jo E.K., 2019, Interplay between host and pathogen: immune defense and beyond, Experimental and Molecular Medicine, 51(12): 1-3. https://doi.org/10.1038/s12276-019-0281-8 Kengradomkij C., Inpankaew T., Kamyingkird K., Wongpanit K., Wongnakphet S., Mitchell T., Xuan X., Igarashi I., Jittapalapong S., and Stich R., 2015, Seroprevalence and risk factors associated with exposure of water buffalo (Bubalus bubalis) to Neospora caninum in northeast Thailand, Veterinary Parasitology, 207(1-2): 156-160. https://doi.org/10.1016/j.vetpar.2014.10.034 Lyashchenko K., Sridhara A., Johnathan-Lee A., Sikar-Gang A., Lambotte P., Esfandiari J., Bernitz N., Kerr T., Miller M., and Waters W., 2020, Differential antigen recognition by serum antibodies from three bovid hosts of Mycobacterium bovis infection, Comparative Immunology Microbiology and Infectious Diseases, 69: 101424. https://doi.org/10.1016/j.cimid.2020.101424 Mabbott N.A., 2018, The influence of parasite infections on host immunity to co-infection with other pathogens, Frontiers in Immunology, 9: 2579. https://doi.org/10.3389/fimmu.2018.02579 Martínez-Burnes J., Barrios-García H., La Fuente V., Corona-González B., Alvarez D., and Romero-Salas D., 2024, Viral diseases in water buffalo (Bubalus bubalis): new insights and perspectives, Animals, 14(6): 845. https://doi.org/10.3390/ani14060845
Molecular Pathogens, 2025, Vol.16, No.1, 1-9 http://microbescipublisher.com/index.php/mp 9 Martucciello A., Balestrieri A., Righi C., Cappelli G., Scoccia E., Grassi C., Brandi S., Rossi E., Galiero G., Gioia D., Fusco G., Feliziani F., De Carlo E., and Petrini S., 2023, Evaluation of an immunization protocol using bovine alphaherpesvirus 1 gE-deleted marker vaccines against bubaline alphaherpesvirus 1 in water buffalo, Vaccines, 11(5): 891. https://doi.org/10.3390/vaccines11050891 Meng Z., Zhai L., Guo Y., Zheng M., Li L., Wen C., Zhang W., and Di W., 2023, Secondary infection of Fasciola gigantica in water buffalo shows a similar pattern of serum cytokine secretion as in primary infection, Frontiers in Veterinary Science, 10: 1109947. https://doi.org/10.3389/fvets.2023.1109947 Panigrahia A., Kumara A., Bhushana B., Ghoshb S., Saravananb B., Sulabha O., Paridac S., and Gaura G., 2016, No change in mRNA expression of immune-related genes in peripheral blood mononuclear cells challenged with Theileria annulata in Murrah buffalo (Bubalus bubalis), Ticks and Tick-Borne Diseases, 7(5): 754-758. https://doi.org/10.1016/j.ttbdis.2016.03.006 Pike V.L., Lythgoe K.A., and King K.C., 2019, On the diverse and opposing effects of nutrition on pathogen virulence, Proceedings of the Royal Society B, 286(1906): 20191220. https://doi.org/10.1098/rspb.2019.1220 Sala J.M., Mansilla F.C., Miraglia M.C., Caspe S., Pérez-Filgueira D., and Capozzo A., 2023, Kinetics of foot-and-mouth disease vaccine-induced antibody responses in water buffalo (Bubalus bubalis): avidity ELISA as an alternative to the virus neutralization test, Frontiers in Veterinary Science, 10: 1162477. https://doi.org/10.3389/fvets.2023.1162477 Shi W., Wei Z.Y., Elsheikha H.M., Zhang F.K., Sheng Z.A., Lu K., Wang D., Huang W., and Zhu X., 2017, Dynamic expression of cytokine and transcription factor genes during experimental Fasciola gigantica infection in water buffalo, Parasites and Vectors, 10: 1-12. https://doi.org/10.1186/s13071-017-2538-1 Shome R., Kilari S., Sahare A., Kalleshamurthy T., Niranjanamurthy H., Shome B., Hiremath J., Misri J., and Rahman H., 2020, Evaluation of the immune responses against reduced doses of Brucella abortus S19 (calfhood) vaccine in water buffalo (Bubalus bubalis) India, Vaccine, 38(45): 7070-7078. https://doi.org/10.1016/j.vaccine.2020.09.010 Silveira J., De Oliveira C., Silvestre B., Albernaz T., Leite R., Barbosa J., Oliveira C., and Ribeiro M., 2016, Molecular assays reveal the presence of Theileria spp. and Babesia spp. in Asian water buffalo (Bubalus bubalis Linnaeus 1758) in the Amazon region of Brazil, Ticks and Tick-Borne Diseases, 7(5): 1017-1023. https://doi.org/10.1016/j.ttbdis.2016.05.009 Smith K., Bernitz N., Goldswain S., Cooper D.V., Warren R., Goosen W., and Miller M., 2020, Optimized interferon-gamma release assays for detection of Mycobacterium bovis infection in African water buffalo (Syncerus caffer), Veterinary Immunology and Immunopathology, 231: 110163. https://doi.org/10.1016/j.vetimm.2020.110163 Vicente-Santos A., Willink B., Nowak K., Civitello D., and Gillespie T., 2023, Host-pathogen interactions under pressure: a review and meta-analysis of stress-mediated effects on disease dynamics, Ecology Letters, 26(11): 2003-2020. https://doi.org/10.1111/ele.14319 Wang W., 2024, Studying the dynamic changes of the immune system through single-cell omics, International Journal of Molecular Medical Science, 14(1): 29-41. https://doi.org/10.5376/ijmms.2024.14.0005 Zhang F.K., Guo A.J., Hou J.L., Sun M.M., Sheng Z.A., Zhang X., Huang W., Elsheikha H., and Zhu X., 2017, Serum levels of cytokines in water buffalo experimentally infected with Fasciola gigantica, Veterinary Parasitology, 244: 97-101. https://doi.org/10.1016/j.vetpar.2017.07.028
Molecular Pathogens, 2025, Vol.16, No.1, 10-18 http://microbescipublisher.com/index.php/mp 10 Case Study Open Access Case Study: Enhancing Cotton’s Resistance to Fungal Pathogens Pingping Yang, Jin Zhang Hainan Institute of Tropical Agricultural Resources, Haikou, 570206, Hainan, China Corresponding author: jin.zhang@hitar.org Molecular Pathogens, 2025, Vol.16, No.1 doi: 10.5376/mp.2025.16.0002 Received: 17 Nov., 2024 Accepted: 05 Jan., 2025 Published: 18 Jan., 2025 Copyright © 2025 Yang and Zhang, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Yang P.P., and Zhang J., 2025, Case study: enhancing cotton’s resistance to fungal pathogens, Molecular Pathogens, 16(1): 10-18 (doi: 10.5376/mp.2025.16.0002) Abstract This study reviews the latest advances in cotton resistance to fungal diseases, particularly Verticillium dahliae and Fusarium oxysporum induced wilt and wilt, using advanced technologies such as genome-wide association analysis (GWAS), CRISPR/Cas9 gene editing, and RNA interference (RNAi). The focus is on genetics and molecular mechanisms, breeding methods, and the application of biotechnology; And emphasized the importance of integrating traditional breeding and modern biotechnology methods to develop disease resistant cotton varieties, and pointed out that future research needs to further explore the roles of plant hormones, long non coding RNAs (lncRNAs), and other factors in disease resistance pathways, in order to promote the development of sustainable agricultural production. Keywords Genetic resistance; Cotton (Gossypiumspp.); Verticillium wilt; Genome editing; Systemic resistance 1 Introduction Cotton (Gossypiumspp.) is a very important cash crop and is the main source of our production of natural fibers. The entire textile industry cannot do without it. Now, about 77 countries around the world are growing cotton, with a planting area of more than 33 million hectares. Many people live on cotton. For example, in India, about 60 million people are related to cotton, and about 6 million are farmers who grow cotton (Boblina et al., 2023). Therefore, cotton is very critical to both agriculture and the global textile industry (McGarry et al., 2024). However, it is not easy to plant cotton and you will encounter a lot of trouble. Especially some fungal diseases, which pose a particularly great threat to cotton. Diseases caused by Verticillium dahliae and Fusarium oxysporum can reduce cotton yields and poor fiber quality (Hu et al., 2021). These bacteria can invade cotton in many ways, such as destroying its immune system or releasing toxins, making it harder for cotton to resist them (Zhu et al., 2023). These diseases not only bring economic losses, but also affect whether cotton can be planted continuously. Therefore, we must find better prevention and treatment methods (Tao et al., 2016). Now, a lot of research is trying to enhance cotton’s disease resistance from a genetic and biochemical perspective. Studies have found that some specific genes can help cotton fight bacteria, such as genes that control lignin synthesis, which can make the cotton's cell wall stronger (Hu et al., 2021). There are also regulators like GhWRKY1, as well as some melatonin-like compounds, that can also help cotton produce more gossypol and lignin, increasing its resistance (Li et al., 2019). In addition, some studies are still using new technologies such as RNA interference and gene stacking, hoping to make cotton more resistant to diseases. This article mainly summarizes some research progress in improving cotton's anti-mycotic ability, especially the content on Verticillium wilt. We also covered the importance of cotton, the disease problems it faces, and the work scientists have done to breed disease-resistant varieties. I hope these contents can provide some inspiration and help for more effective and sustainable disease prevention and control methods in the future. 2 Overview of Major Fungal Diseases in Cotton Cotton is a very important crop in the textile industry, but it is prone to several fungal diseases. These diseases will reduce yields and will also affect the quality of cotton. The most serious diseases include wilt, root rot (caused by Rhizoctonia solani), and anthracnose. Most of these diseases are transmitted through the soil, so it is particularly difficult to prevent and treat.
Molecular Pathogens, 2025, Vol.16, No.1, 10-18 http://microbescipublisher.com/index.php/mp 11 2.1 Fusarium wilt in cotton The disease of cotton is mainly caused by a fungus called Fusarium oxysporumf. sp. vasinfectum, referred to as FOV. This disease is found in many countries, especially in the western and southwestern United States, and has a great impact on cotton yield (Chen et al., 2024). Sick cotton usually turns yellow at first, then wilt, and eventually the whole plant dies. There is a mutation type called FOV4, which is more toxic. Researchers have discovered it in the San Joaquin Valley of California and in New Mexico. This situation has forced everyone to speed up and breed new cotton varieties that can resist diseases (Zhu et al., 2021). 2.2 Rhizoctonia solani (root rot) in cotton Cotton is also prone to a disease called root rot, which is caused by Rhizoctonia solani. This disease will cause the roots to rot, causing the seedlings to die, the entire plant to grow poorly, and the final yield reduction is very serious. Although some studies have not mentioned much, farmers who grow cotton are still worried about this problem because it will directly affect the survival rate of seedlings and the health of the entire land. 2.3 Colletotrichumspp. (anthracnose) in cotton Anthracnose is another common fungal disease caused by Colletotrichumspecies. It will attack the cotton bolls, leaves and stems, causing them to appear lesions and even drop leaves early. Humid weather is particularly prone to spreading this disease. Although previous studies have not talked much about anthrax, it still needs to be paid attention to because it may cause serious production cuts (Wu, 2024). 2.4 Symptoms, transmission mechanisms, and ecological impacts of diseases Cotton with blight will have some obvious symptoms, such as yellowing, withering, and even the entire plant will die. This disease is caused by fungi in the soil, which turns into thick wall spores hidden in the soil and is difficult to remove (Dhage and Garg, 2023). There is also a bacteria called Rhizoctonia solani, which can cause root rot and prevent cotton from growing tall or growing well. And the Colletotrichum gossypii will cause black spots to grow on the bolls and leaves, which is Anthracnose. In severe cases, the leaves will fall and the yield will decrease. These bacteria are generally transmitted through soil or infected plant residues. Therefore, it becomes very important to change crops and do a good job of soil management. These diseases also have an impact on the ecology. For example, there are fewer biological species in some places. Moreover, in order to control diseases, farmers often have to use more pesticides, which may cause new problems to the environment. 3 Genetic Basis for Enhancing Disease Resistance 3.1 Identification and functional study of resistance genes 3.1.1 Methods for identifying resistance genes In order to find out the disease-resistant genes in cotton, scientists have used many genomic methods. Like Genome-wide association analysis (GWAS) and using special populations (such as advanced generation hybrid population MAGIC) to find genes. These methods have helped us discover some important gene regions related to cotton blight (Zhang et al., 2019; Zhu et al., 2022). Some specific genes, such as GhnsLTPsA10, have been shown to be related to cotton's resistance to verticillium wilt. The researchers used transcriptome analysis and physiological experiments to see how this gene changes before and after infection. They found that once the bacteria are infected, the expression of this gene in the leaves will increase significantly, which means it may be related to disease prevention. Then, they also compared genetically modified cotton with ordinary cotton. The results show that the lesions on the leaves of cotton overexpressing GhnsLTPsA10 are smaller, indicating that this gene can indeed help cotton better resist bacteria (Figure 1) (Chen et al., 2021). 3.1.2 Functional validation and classification of resistance genes In order to confirm whether a gene has a disease-resistant effect, scientists often use two methods: one is to make the gene express more, and the other is to make it “silence” and not express it. For example, there is a laccase gene called GhLAC15. After being overexpressed, cotton will produce more lignin and the cell wall will become harder,
Molecular Pathogens, 2025, Vol.16, No.1, 10-18 http://microbescipublisher.com/index.php/mp 12 which will be more resistant to disease (Zhang et al., 2018). Another gene, GhWRKY1-like, is a regulatory gene that can also improve disease resistance by affecting lignin synthesis (Hu et al., 2021). These experiments indicate: If you want cotton to resist disease, you must first find out the genes and verify whether it is useful. Figure 1GhnsLTPsA10negatively regulates the resistance of aphids and cotton bollworms Image caption: (a) The tissue-specific expression of GhnsLTPsA10 in NDM23 was analyzed by qRT PCR 24 hours after infection (hai). (b, c) Conduct non selective feeding assays using wild-type and transgenic Arabidopsis and cotton plants. (d) Selective feeding test for cotton bollworm. (e) Cotton selection aphid feeding determination. (f) Determination of cotton feeding selection for cotton bollworm (Adopted from Chen et al., 2021) 3.2 Application of cotton genome editing technologies 3.2.1 Application of CRISPR-Cas9 technology in cotton CRISPR-Cas9 is a very popular gene editing technology nowadays. It can “precisely use” the DNA of the crop to change bad genes, or add disease-resistant functions. Although there are not many examples of directly using CRISPR to transform cotton disease resistance, success stories on other crops have proven its potential (Wang and Zhang, 2024). So we have reason to believe that CRISPR can also play a role in cotton. 3.2.2 Case studies on improving resistance through genome editing Although CRISPR is not used much, there is a similar method called HIGS (host-induced gene silencing), which has also been used on cotton. HIGS practices are to let cotton actively “turn off” the key genes of bacteria. For example, some studies have “silenced” certain virulence genes of Verticillium dahliae, so that the bacteria are not that powerful and cotton is more resistant to disease (Wei et al., 2020). This shows that gene editing technology can indeed help prevent diseases. 3.3 Mechanisms of fungal toxins and strategies for cotton resistance Fungi produces some toxins that can interfere with the normal activity of the plant, such as making its defense worse. If we want cotton to be more resistant to disease, we must first figure out how these toxins work. Studies have found that a plant hormone called strigolactones can help. It can work with other hormones, such as abscisic acid and jasmonic acid, making the disease-resistant genes in cotton more active and the activity of antioxidant enzymes can also increase. In this way, cotton will be more resistant to Verticillium wilt (Han et al., 2024). There are also scientists trying to use a new method called “fusion antimicrobial peptide”. This substance can specifically attack components in the cell membrane of fungi, such as ergosterol. At present, this method is quite promising (Tong et al., 2020). These studies show that we are not just relying on traditional breeding or pesticides to prevent diseases. Scientists are still looking for solutions from a molecular perspective, hoping to fight fungal diseases more effectively.
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