بررسی قابلیت ریزمولکول‎های گیاهی در مهار پروتئین‎های FnBPA و سورتاز A باکتری استافیلوکوکوس اورئوس با استفاده از روش‎های داکینگ مولکولی و تعیین حداقل غلظت مهارکنندگی

نوع مقاله : مقاله پژوهشی

نویسندگان

1 گروه علوم دامی، دانشکده کشاورزی، مجتمع آموزش عالی تربت جام - ایران

2 گروه میکروب شناسی و ویروس شناسی، دانشکده پزشکی، دانشگاه علوم پزشکی مشهد، ایران

3 محقق، مرکز تحقیقات سندرم متابولیک، دانشگاه علوم پزشکی مشهد، ایران

4 گروه علوم دامی، دانشکده کشاورزی، دانشگاه فردوسی مشهد، ایران

چکیده

هدف: ورم پستان یک بیماری عفونی شایع گاوهای شیری در سراسر جهان است که موجب التهاب غدد پستانی می‌شود. کنترل این بیماری به دلیل ایجاد مقاومت آنتی ‌بیوتیکی چالش برانگیز است. معرفی ترکیبات جایگزین یا مکمل آنتی ‌بیوتیک‌ها می‌تواند راه حلی پایدار در پیشگیری و درمان این بیماری باشد. هدف از این مطالعه ارزیابی اثربخشی میکرومولکول‌های گیاهی در مهار باکتری استافیلوکوکوس اورئوس، یکی از عوامل مهم ایجاد ورم پستان، از طریق داکینگ مولکولی و تعیین حداقل غلظت مهاری (MIC) بود.
مواد و روش‌ها: ساختارهای سه‌بعدی پروتئین‌های هدف، شامل FnBPA و sortase A، از پایگاه‌های داده ساختاری استخراج و پس از مدل‌سازی و بهینه‌سازی انرژی، ساختارها اعتبارسنجی شدند. کتابخانه‌ای متشکل از ۴۶۰ میکرومولکول گیاهی از پایگاه‌های داده معتبر جمع‌آوری و ساختارهای سه‌بعدی برای آن‌ها تهیه شد. غربالگری اولیه ترکیبات با استفاده از ابزارهای محاسباتی و بر اساس خواص فارماکودینامیکی و شاخص‌های ADMET انجام شد. سپس، داکینگ مولکولی با نرم‌افزار PyRx نسخه ۰.۸ برای بررسی برهمکنش‌های لیگاند-گیرنده و محاسبه انرژی‌های اتصال انجام گرفت. در نهایت، دو ترکیب انتخاب شده، کورکومین و ایندیگو کارمین، با استفاده از روش رقت در آگار برای تعیین حداقل غلظت مهاری (MIC) در برابر استافیلوکوکوس اورئوس در شرایط آزمایشگاهی ارزیابی شدند.
نتایج: نتایج اعتبارسنجی ساختار پروتئین، کیفیت مدل‌ها را تأیید کرد. چندین مولکول کوچک با انرژی‌های اتصال مطلوب (در محدوده ۶- تا ۱۰- کیلوکالری بر مول) در بین ۴۶۰ ترکیب شناسایی شدند. ترکیباتی مانند ایندیگو، گلیاسپرین A، سانگوینارین، کامپتوتسین و ایندیگو کارمین قوی‌ترین میل اتصال را به FnBPA نشان دادند که ناشی از پیوندهای هیدروژنی و برهمکنش‌های آبگریز پایدار با آمینواسیدهای گیرنده بودند. سورتاز A با چندین مولکول کوچک که انرژی‌های اتصال آنها از ۶.۴- تا ۷.۳- کیلوکالری بر مول متغیر بود، پیوندهای هیدروژنی و آبگریز تشکیل داد. نتایج آزمایشگاهی نشان داد که کورکومین و ایندیگو کارمین رشد باکتری را مهار کرده و مقادیر MIC آن‌ها نشان‌دهنده فعالیت ضد باکتریایی موثر آن‌ها بود.
نتیجه‌گیری: یافته‌های این مطالعه نشان داد که برخی از ریزمولکول‌های گیاهی به طور قابل توجهی عوامل بیماری‌زای کلیدی در استافیلوکوکوس اورئوس را می‌توانند مهار ‌کنند. ترکیب نتایج محاسباتی و آزمایشگاهی نشان می‌دهد که این مولکول‌ها می‌توانند کاندیداهای امیدوارکننده‌ای برای توسعه استراتژی‌های جدید کنترل ورم پستان، کاهش وابستگی به آنتی‌بیوتیک‌ها و راه حلی برای چالش مقاومت آنتی بیوتیکی باشند.

کلیدواژه‌ها

عنوان مقاله [English]

Evaluation of plant-derived small molecules targeting FnBPA and sortase A of Staphylococcus aureus through molecular docking and minimum inhibitory concentration assays

نویسندگان [English]

  • Reza Tohidi 1
  • Kiarash Ghazvini 2
  • Marzieh Gharouni 3
  • Mohammadreza Nassiri 4
1 Dept. of Animal Science, Faculty of Agriculture, University of Torbat-e Jam, Iran
2 Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
3 Researcher, Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Iran
4 Department of Animal Science, Faculty of Agriculture, Ferdowsi University of Mashhad, Mashhad, Iran
چکیده [English]

Objective
Mastitis, an inflammation of the mammary glands, is a common infectious disease of dairy cows worldwide. Controlling this disease is challenging due to the emergence of antibiotic resistance. Using alternative or complementary compounds alongside antibiotics can be a sustainable solution for preventing and treating this disease. This study aimed to evaluate the effectiveness of plant-derived micromolecules in inhibiting Staphylococcus aureus, an important cause of mastitis, using molecular docking and determining the minimum inhibitory concentration (MIC).

Materials and methods
The 3D structures of the target proteins, including FnBPA and sortase A, were extracted from structural databases. After modeling and energy optimization, the structures were validated. A library of 460 plant-derived micromolecules was collected from reliable databases, and 3D structures were prepared for each molecule. Initial screening of the compounds was performed using computational tools based on pharmacodynamic properties and ADMET indices. Then, molecular docking was performed using PyRx version 0.8 software to investigate ligand-receptor interactions and calculate binding energies. Finally, the minimum inhibitory concentration (MIC) of two selected compounds, curcumin and indigo carmine, against Staphylococcus aureus in vitro was determined using the agar dilution method.
Results
The results of the protein structure validation process confirmed the quality of the models. Among 460 compounds, several small molecules with favorable binding energies in the range of -6 to -10 kcal/mol were identified. Compounds such as indigo, gliasperin A, sanguinarine, camptothecin, and indigo carmine exhibited the strongest binding affinity to FnBPA due to hydrogen bonds and stable hydrophobic interactions with receptor amino acids. Sortase A formed hydrogen and hydrophobic bonds with several small molecules whose binding energies ranged from -6.4 to -7.3 kcal/mol. In vitro results showed that curcumin and indigo carmine inhibited bacterial growth; their MIC values indicated effective antibacterial activity.
Conclusions
The findings of this study illustrated that several plant-derived micromolecules can effectively inhibit key pathogenic factors of Staphylococcus aureus. Combining computational and experimental results suggest that these compounds are promising candidates for the development of novel strategies to control mastitis and reduce reliance on antibiotics. They can also help address the growing challenge of antibiotic resistance.

کلیدواژه‌ها [English]

  • Mastitis
  • Staphylococcus aureus
  • small molecule
  • molecular docking
  • MIC

مراجع

Abebe, R., Hatiya, H., Abera, M., Megersa, B., & Asmare, K. (2016). Bovine mastitis: Prevalence, risk factors and isolation of Staphylococcus aureus in dairy herds at Hawassa milk shed, South Ethiopia. BMC Veterinary Research, 12(1), Article 270. https://doi.org/10.1186/s12917-016-0905-3
Adamczak, A., Ożarowski, M., & Karpiński, T. M. (2020). Curcumin, a natural antimicrobial agent with strain-specific activity. Pharmaceuticals, 13(7), Article 153. https://doi.org/10.3390/ph13070153
Al-Dhabi, N. A., Balachandran, C., Raj, M. K., Duraipandiyan, V., Muthukumar, C., Ignacimuthu, S., Khan, I. A., & Rajput, V. S. (2012). Antimicrobial, antimycobacterial and antibiofilm properties of Couroupita guianensis Aubl. fruit extract. BMC Complementary and Alternative Medicine, 12, Article 242. https://doi.org/10.1186/1472-6882-12-242
Al-Gethami, W., & Al-Qasmi, N. (2021). Antimicrobial activity of Ca-alginate/chitosan nanocomposite loaded with camptothecin. Polymers, 13(20), Article 3559. https://doi.org/10.3390/polym13203559
Algharib, S. A., Dawood, A., & Xie, S. (2020). Nanoparticles for treatment of bovine Staphylococcus aureus mastitis. Drug Delivery, 27(1), 292–308. https://doi.org/10.1080/10717544.2020.1724209
Artursson, K., Söderlund, R., Liu, L., Monecke, S., & Schelin, J. (2016). Genotyping of Staphylococcus aureus in bovine mastitis and correlation to phenotypic characteristics. Veterinary Microbiology, 193, 156–161. https://doi.org/10.1016/j.vetmic.2016.08.012
Arung, E. T., Sinamabela, J. R., Rosamah, E., Kusuma, I. W., Kuspradini, H., Alam, A. E., & others. (2015). Antioxidant and antimelanogenesis activities of glyasperin A from Macaranga pruinosa leaves. Natural Product Communications, 10(1), 1–5.
Ashraf, S., Cheng, J., & Zhao, X. (2017). Clumping factor A of Staphylococcus aureus interacts with AnnexinA2 on mammary epithelial cells. Scientific Reports, 7, Article 40608. https://doi.org/10.1038/srep40608
Begum, K., Motobayashi, T., Hasan, N., Appiah, K. S., Shammi, M., & Fujii, Y. (2020). Indigo as a plant growth inhibitory chemical from the fruit pulp of Couroupita guianensis Aubl. Agronomy, 10(9), Article 1388. https://doi.org/10.3390/agronomy10091388
Brouillette, E., Talbot, B. G., & Malouin, F. (2003). The fibronectin-binding proteins of Staphylococcus aureus may promote mammary gland colonization in a lactating mouse model of mastitis. Infection and Immunity, 71(4), 2292–2295. https://doi.org/10.1128/IAI.71.4.2292-2295.2003
Cheng, W. N., & Han, S. G. (2020). Bovine mastitis: Risk factors, therapeutic strategies, and alternative treatments - A review. Asian-Australasian Journal of Animal Sciences, 33(11), 1699–1713. https://doi.org/10.5713/ajas.20.0156
Coleman, K. J., Ngor, E., Reynolds, K., Quinn, V. P., Koebnick, C., Young, D. R., Sternfeld, B., & Sallis, R. E. (2012). Initial validation of an exercise "vital sign" in electronic medical records. Medicine and Science in Sports and Exercise, 44(11), 2071–2076. https://doi.org/10.1249/MSS.0b013e3182630ec1
De Kievit, T. R., Gillis, R., Marx, S., Brown, C., & Iglewski, B. H. (2001). Quorum-sensing genes in Pseudomonas aeruginosa biofilms: Their role and expression patterns. Applied and Environmental Microbiology, 67(4), 1865–1873. https://doi.org/10.1128/AEM.67.4.1865-1873.2001
Dong, Q., Luo, J., Qiu, W., Cai, L., Anjum, S. I., Li, B., Hou, M., Xie, G., & Sun, G. (2016). Inhibitory effect of camptothecin against rice bacterial brown stripe pathogen Acidovorax avenae subsp. avenae RS-2. Molecules, 21(8), Article 978. https://doi.org/10.3390/molecules21080978
Edge, C., Baker, L., Smenderovac, E., Heartz, S., & Emilson, E. (2022). Tebufenozide has limited direct effects on simulated aquatic communities. Ecotoxicology, 31(8), 1231–1240. https://doi.org/10.1007/s10646-022-02582-y
Exel, C. E., Halasa, T., Koop, G., Steeneveld, W., Lam, T. J. G. M., Benedictus, L., & Gussmann, M. (2022). A stochastic modelling approach to determine the effect of diverse Staphylococcus aureus strains on the economic and epidemiological outcomes of mastitis intervention strategies in dairy cattle. Preventive Veterinary Medicine, 199, Article 105566. https://doi.org/10.1016/j.prevetmed.2021.105566
Ferreira de Freitas, R., & Schapira, M. (2017). A systematic analysis of atomic protein-ligand interactions in the PDB. MedChemComm, 8(10), 1970–1981. https://doi.org/10.1039/c7md00381a
Fleischer, P., Metzner, M., Beyerbach, M., Hoedemaker, M., & Klee, W. (2001). The relationship between milk yield and the incidence of some diseases in dairy cows. Journal of Dairy Science, 84(9), 2025–2035. https://doi.org/10.3168/jds.S0022-0302(01)74646-2
Givens, D. I. (2020). MILK Symposium review: The importance of milk and dairy foods in the diets of infants, adolescents, pregnant women, adults, and the elderly. Journal of Dairy Science, 103(11), 9681–9699. https://doi.org/10.3168/jds.2020-18296
Gomes, F., & Henriques, M. (2016). Control of bovine mastitis: Old and recent therapeutic approaches. Current Microbiology, 72(4), 377–382. https://doi.org/10.1007/s00284-015-0958-8
Górski, M., Niedźwiadek, J., & Magryś, A. (2022). Antibacterial activity of curcumin – a natural phenylpropanoid dimer from the rhizomes of Curcuma longa L. and its synergy with antibiotics. Annals of Agricultural and Environmental Medicine, 29(3), 394–400. https://doi.org/10.26444/aaem/148393
Guler, A. (2025). Thermodynamic and structural signatures of arginine self-assembly across concentration regimes. Processes, 13(7), Article 1998. https://doi.org/10.3390/pr13071998
Gunes, H., Gulen, D., Mutlu, R., Gumus, A., Tas, T., & Topkaya, A. E. (2016). Antibacterial effects of curcumin: An in vitro minimum inhibitory concentration study. Toxicology and Industrial Health, 32(2), 246–250. https://doi.org/10.1177/0748233713498458
Hogeveen, H., Steeneveld, W., & Wolf, C. A. (2019). Production diseases reduce the efficiency of dairy production: A review of the results, methods, and approaches regarding the economics of mastitis. Annual Review of Resource Economics, 11, 289–312. https://doi.org/10.1146/annurev-resource-100518-093954
Jacobitz, A. W., Kattke, M. D., Wereszczynski, J., & Clubb, R. T. (2017). Sortase transpeptidases: Structural biology and catalytic mechanism. Advances in Protein Chemistry and Structural Biology, 109, 223–264. https://doi.org/10.1016/bs.apcsb.2017.04.008
Johnzon, C. F., Artursson, K., Söderlund, R., Guss, B., Rönnberg, E., & Pejler, G. (2016). Mastitis pathogens with high virulence in a mouse model produce a distinct cytokine profile in vivo. Frontiers in Immunology, 7, Article 368. https://doi.org/10.3389/fimmu.2016.00368
Jung, H. J., Seu, Y. B., & Lee, D. G. (2007). Candicidal action of resveratrol isolated from grapes on human pathogenic yeast C. albicans. Journal of Microbiology and Biotechnology, 17(8), 1324–1329.
Kalli, S., Araya-Cloutier, C., Hageman, J., & Vincken, J. P. (2021). Insights into the molecular properties underlying antibacterial activity of prenylated (iso)flavonoids against MRSA. Scientific Reports, 11(1), Article 14180. https://doi.org/10.1038/s41598-021-92964-9
Kathuria, S. V., Chan, Y. H., Nobrega, R. P., Özen, A., & Matthews, C. R. (2016). Clusters of isoleucine, leucine, and valine side chains define cores of stability in high-energy states of globular proteins: Sequence determinants of structure and stability. Protein Science, 25(3), 662–675. https://doi.org/10.1002/pro.2860
Keane, O. M. (2019). Symposium review: Intramammary infections—Major pathogens and strain associated complexity. Journal of Dairy Science, 102(5), 4713–4726. https://doi.org/10.3168/jds.2018-15326
Khan, M., & Khan, A. (2006). Basic facts of mastitis in dairy animals: A review. Pakistan Veterinary Journal, 26(4), 204–208.
Komine, Y., Komine, K., Kai, K., Itagaki, M., Kuroishi, T., Aso, H., Obara, Y., & Kumagai, K. (2006). Effect of combination therapy with lactoferrin and antibiotics against staphylococcal mastitis on drying cows. The Journal of Veterinary Medical Science, 68(3), 205–211. https://doi.org/10.1292/jvms.68.205
Kovačević, Z., Samardžija, M., Horvat, O., Tomanić, D., Radinović, M., Bijelić, K., Vukomanović, A. G., & Kladar, N. (2022). Is there a relationship between antimicrobial use and antibiotic resistance of the most common mastitis pathogens in dairy cows? Antibiotics, 12(1), Article 3. https://doi.org/10.3390/antibiotics12010003
Krieger, E., Joo, K., Lee, J., Lee, J., Raman, S., Thompson, J., Tyka, M., Baker, D., & Karplus, K. (2009). Improving physical realism, stereochemistry, and side-chain accuracy in homology modeling: Four approaches that performed well in CASP8. Proteins, 77(Suppl 9), 114–122. https://doi.org/10.1002/prot.22570
Liu, N., Li, L., Zhu, X., Ling, Z., Feng, J., Hu, Y., Wang, Y., Mou, L., & Wang, Y. (2016). A high content screening assay to identify compounds with anti-epithelial-mesenchymal transition effects from the Chinese herbal medicine Tong-Mai-Yang-Xin-Wan. Molecules, 21(10), Article 1340. https://doi.org/10.3390/molecules21101340
Lopes, T. S., Fontoura, P. S., Oliveira, A., Rizzo, F. A., Silveira, S., & Streck, A. F. (2020). Use of plant extracts and essential oils in the control of bovine mastitis. Research in Veterinary Science, 131, 186–193. https://doi.org/10.1016/j.rvsc.2020.04.025
Marraffini, L. A., Dedent, A. C., & Schneewind, O. (2006). Sortases and the art of anchoring proteins to the envelopes of gram-positive bacteria. Microbiology and Molecular Biology Reviews, 70(1), 192–221. https://doi.org/10.1128/MMBR.70.1.192-221.2006
Martino, E., Della Volpe, S., Terribile, E., Benetti, E., Sakaj, M., Centamore, A., ... & Pacifico, S. (2017). The long story of camptothecin: From traditional medicine to drugs. Bioorganic & Medicinal Chemistry Letters, 27(4), 701–707. https://doi.org/10.1016/j.bmcl.2016.12.085
Menchinelli, G., Squitieri, D., Magrì, C., De Maio, F., D’Inzeo, T., Cacaci, M., De Angelis, G., Sanguinetti, M., & Posteraro, B. (2024). Verification of the Vitek Reveal system for direct antimicrobial susceptibility testing in Gram-negative positive blood cultures. Antibiotics, 13(11), Article 1058. https://doi.org/10.3390/antibiotics13111058
Nishida, M., Terabayashi, T., Matsuoka, S., et al. (2022). Mechanism of action of non-camptothecin inhibitor Genz-644282 in topoisomerase I inhibition. Communications Biology, 5(1), Article 982. https://doi.org/10.1038/s42003-022-03920-w
Nitulescu, G., Nicorescu, I. M., Olaru, O. T., Ungurianu, A., Mihai, D. P., Zanfirescu, A., Nitulescu, G. M., & Margina, D. (2017). Molecular docking and screening studies of new natural sortase A inhibitors. International Journal of Molecular Sciences, 18(10), Article 2217. https://doi.org/10.3390/ijms18102217
Pascu, C., Herman, V., Iancu, I., & Costinar, L. (2022). Etiology of mastitis and antimicrobial resistance in dairy cattle farms in the western part of Romania. Antibiotics, 11(1), Article 57. https://doi.org/10.3390/antibiotics11010057
Patronov, A., Salamanova, E., Dimitrov, I., Flower, D. R., & Doytchinova, I. (2014). Histidine hydrogen bonding in MHC at pH 5 and pH 7 modeled by molecular docking and molecular dynamics simulations. Current Computer-Aided Drug Design, 10(1), 41–49.
Pei, J., Xiong, L., Wu, X., Chu, M., Bao, P., Ge, Q., & Guo, X. (2025). Bovine lactoferricin exerts antibacterial activity against four Gram-negative pathogenic bacteria by transforming its molecular structure. Frontiers in Cellular and Infection Microbiology, 15, Article 1508895. https://doi.org/10.3389/fcimb.2025.1508895
Pereyra, E. A., Picech, F., Renna, M. S., Baravalle, C., Andreotti, C. S., Russi, R., Calvinho, L. F., Diez, C., & Dallard, B. E. (2016). Detection of Staphylococcus aureus adhesion and biofilm-producing genes and their expression during internalization in bovine mammary epithelial cells. Veterinary Microbiology, 183, 69–77. https://doi.org/10.1016/j.vetmic.2015.12.002
Qu, Q., Huang, X., Zhu, Z., Wang, J., Zhao, M., Cui, W., Zheng, Y., Liu, Y., Chen, X., Zhang, Z., Dong, N., Dong, C., & Li, Y. (2025). Targeting membrane integrity and imidazoleglycerol-phosphate dehydratase: Sanguinarine multifaceted approach against Staphylococcus aureus biofilms. Phytomedicine, 138, Article 156428. https://doi.org/10.1016/j.phymed.2025.156428
Ragasa, C. Y., Galian, R. A. F., Ebajo, V. D., & others. (2015). Propolins and glyasperin A from stingless bee nests. Revista Brasileira de Farmacognosia, 25(2), 177–179. https://doi.org/10.1016/j.bjp.2015.03.006
Raza, S., Bończak, B., Atamas, N., Karpińska, A., Ratajczyk, T., Łoś, M., Hołyst, R., & Paczesny, J. (2025). The activity of indigo carmine against bacteriophages: An edible antiphage agent. Applied Microbiology and Biotechnology, 109(1), Article 24. https://doi.org/10.1007/s00253-025-13414-4
Schneewind, O., & Missiakas, D. (2019). Sortases, surface proteins, and their roles in Staphylococcus aureus disease and vaccine development. Microbiology Spectrum, 7(1). https://doi.org/10.1128/microbiolspec.PSIB-0004-2018
Sharun, K., Dhama, K., Tiwari, R., Gugjoo, M. B., Iqbal Yatoo, M., Patel, S. K., Pathak, M., Karthik, K., Khurana, S. K., Singh, R., Puvvala, B., Amarpal, Singh, R., Singh, K. P., & Chaicumpa, W. (2021). Advances in therapeutic and managemental approaches of bovine mastitis: A comprehensive review. The Veterinary Quarterly, 41(1), 107–136. https://doi.org/10.1080/01652176.2021.1882713
Shin, M., Mun, D., Choi, H. J., Kim, S., Payne, S. M., & Kim, Y. (2021). Identification of a new antimicrobial agent against bovine mastitis-causing Staphylococcus aureus. Journal of Agricultural and Food Chemistry, 69(34), 9968–9978. https://doi.org/10.1021/acs.jafc.1c02738
Simonin, A., Montalbetti, N., Gyimesi, G., Pujol-Giménez, J., & Hediger, M. A. (2015). The hydroxyl side chain of a highly conserved serine residue is required for cation selectivity and substrate transport in the glial glutamate transporter GLT-1/SLC1A2. The Journal of Biological Chemistry, 290(51), 30464–30474. https://doi.org/10.1074/jbc.M115.689836
Speziale, P., & Pietrocola, G. (2020). The multivalent role of fibronectin-binding proteins A and B (FnBPA and FnBPB) of Staphylococcus aureus in host infections. Frontiers in Microbiology, 11, Article 2054. https://doi.org/10.3389/fmicb.2020.02054
Stemberk, V., Jones, R. P., Moroz, O., Atkin, K. E., Edwards, A. M., Turkenburg, J. P., Leech, A. P., Massey, R. C., & Potts, J. R. (2014). Evidence for steric regulation of fibrinogen binding to Staphylococcus aureus fibronectin-binding protein A (FnBPA). The Journal of Biological Chemistry, 289(18), 12842–12851. https://doi.org/10.1074/jbc.M113.543546
Suarez-Lopez, Y. A., Pons, B. de la N., Fernández Martín, F., & Rodríguez Hernández, P. (2016). Comparative study of the behavior of six strains of arbuscular mycorrhizal fungi in their interaction with tomato (Lycopersicon esculentum M. var “Amalia”). Ecología Aplicada, 3(1-2), 162–171. https://doi.org/10.21704/rea.v3i1-2.286
Suarez, J. L., & Viana, R. M. (2024). Tebufenozide has limited direct effects on simulated aquatic communities. Ecotoxicology, 31(8), 1231–1240. https://doi.org/10.1007/s10646-022-02582-y
Talbot, B. G., & Lacasse, P. (2005). Progress in the development of mastitis vaccines. Livestock Production Science, 98(1-2), 101–113. https://doi.org/10.1016/j.livprodsci.2005.10.018
Theerawatanasirikul, S., Thangthamniyom, N., Kuo, C. J., Semkum, P., Phecharat, N., Chankeeree, P., & Lekcharoensuk, P. (2021). Natural phytochemicals, luteolin and isoginkgetin, inhibit 3C protease and infection of FMDV, in silico and in vitro. Viruses, 13(11), Article 2118. https://doi.org/10.3390/v13112118
Tomanić, D., Samardžija, M., & Kovačević, Z. (2023). Alternatives to antimicrobial treatment in bovine mastitis therapy: A review. Antibiotics, 12(4), Article 683. https://doi.org/10.3390/antibiotics12040683
Tong, X., Barkema, H. W., Nobrega, D. B., Xu, C., Han, B., Zhang, C., Yang, J., Li, X., & Gao, J. (2025). Virulence of bacteria causing mastitis in dairy cows: A literature review. Microorganisms, 13(1), Article 167. https://doi.org/10.3390/microorganisms13010167
Trujillo, C., Rodriguez-Sanz, A. A., & Rozas, I. (2015). Aromatic amino acids-guanidinium complexes through cation-π interactions. Molecules, 20(5), 9214–9228. https://doi.org/10.3390/molecules20059214
Tyagi, P., Singh, M., Kumari, H., Kumari, A., & Mukhopadhyay, K. (2015). Bactericidal activity of curcumin I is associated with damaging of bacterial membrane. PLOS ONE, 10(3), Article e0121313. https://doi.org/10.1371/journal.pone.0121313
USDA. (2025). Dairy: World markets and trade. https://esmis.nal.usda.gov/publication/dairy-world-markets-and-trade
Vrieling, M., Koymans, K. J., Heesterbeek, D. A., Aerts, P. C., Rutten, V. P., de Haas, C. J., van Kessel, K. P., Koets, A. P., Nijland, R., & van Strijp, J. A. (2015). Bovine Staphylococcus aureus secretes the leukocidin LukMF' to kill migrating neutrophils through CCR1. mBio, 6(3), Article e00335. https://doi.org/10.1128/mBio.00335-15
Zhang, Q. Y., Yan, Z. B., Meng, Y. M., Hong, X. Y., Shao, G., Ma, J. J., Cheng, X. R., Liu, J., Kang, J., & Fu, C. Y. (2021). Antimicrobial peptides: Mechanism of action, activity and clinical potential. Military Medical Research, 8(1), Article 48. https://doi.org/10.1186/s40779-021-00343-2
Zheng, D., Huang, C., Huang, H., Zhao, Y., Khan, M. R. U., Zhao, H., & Huang, L. (2020). Antibacterial mechanism of curcumin: A review. Chemistry & Biodiversity, 17(8), Article e2000171. https://doi.org/10.1002/cbdv.202000171
مجله بیوتکنولوژی کشاورزی
دوره 18، شماره 4
دی 1405
صفحه 87-110

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