MYCOTOXIN INDUCED ANTIBIOTIC RESISTANCE, AN UNSUSPECTED PUBLIC HEALTH IMPACT: A PERSPECTIVE REVIEW


307 / 128

Authors

  • Prathap Kumar Kothapalli Centre for Ethno-Veterinary Science and Practice, The University of Trans-Disciplinary Health Sciences and Technology Bangalore, Karnataka, India
  • M.N. Balakrishna Nair Centre for Ethno-Veterinary Science and Practice, The University of Trans-Disciplinary Health Sciences and Technology, Bangalore
  • N. Punniyamurthy Centre for Ethno-Veterinary Science and Practice, The University of Trans-Disciplinary Health Sciences and Technology, Bangalore

https://doi.org/10.56093/ijvasr.v50i4.127556

Keywords:

Mycotoxins, Antibacterial activity, Cross-resistance, Induced antibiotic-resistant

Abstract

Resistance-to-antibiotics (ABR) in bacteria is an ever increasing critical global public health concern, as is the prevalence of mycotoxins in human food and animal feed. Mycotoxins are toxins produced by fungi, and so are antibiotics, albeit some soil bacteria also produce antibiotics. While fungal compounds toxic to humans and animals were categorised as mycotoxins, compounds having bactericidal/bacteriostatic activity were pharmacologically used as antibiotics. Nevertheless, the line of demarcation between antibiotics and mycotoxins is not absolute, as many mycotoxins possess antibiotic properties. However, until now mycotoxins were usually not-suspected to induce cross-resistance to antibiotics. The current article demonstrates the plausible mechanistic link for the induction of cross-resistance by mycotoxins to antibiotics. Evidence presented shows that in addition to common origin both mycotoxins and antibiotics have similar chemical structures, genetic backbone, biosynthetic pathway as well as role in the life of producing organism and even induce similar resistance mechanisms in bacteria, scientifically substantiating that mycotoxin induced ABR is a plausible phenomenon. Further the unavoidable presence of mycotoxins in animal feed albeit at low levels, mimics long-term exposure of commensal bacteria in farm animals to antibiotic-growth-promoters at low levels. Additionally, chronic low-level antibiotic exposure in animals is argued to be a serious factor contributing to antibiotic-resistant bacteria in humans. Finally the article provides experimental design to help evaluate the mycotoxin-induced-ABR. The given scientific evidence necessitates future investigations through appropriate studies to confirm the potential of mycotoxins as critical inducers of ABR, from possibility to plausibility.

Downloads

Download data is not yet available.

References

Ali-Vehmas, T., Rizzo, A., Westermarck, T. and Atroshi, F. (1998). Measurement of Antibacterial Activities of T-2 Toxin, Deoxynivalenol, Ochratoxin A, Matoxin B1 and Fumonisin B1 Using Microtitration Tray-based Turbidimetric Techniques. Journal of Veterinary Medicine, 458: 453–458.

Alshannaq, A. and Yu, J.H. (2017). Occurrence, toxicity, and analysis of major mycotoxins in food. International Journal of Environmental Research and Public Health, 14(6). https://doi. org/10.3390/ijerph14060632

Baines, D., Sumarah, M., Kuldau, G., Juba, J., Mazza, A. and Masson, L. (2013). Aflatoxin, fumonisin and shiga toxin- producing Escherichia coli Infections in calves and the effectiveness of Celmanax®/Dairyman’s choiceTM. Applications to Eliminate Morbidity and Mortality Losses, 1872–1895. https:// doi.org/10.3390/toxins5101872

Barker, K.F. (1999). Antibiotic resistance: a current perspective. British Journal of Clinical Pharmacology, 48(2): 109–124.

Bennett, J.W. and Klich, M. (2003). Mycotoxins. Clinical Microbiology Reviews, 16(3), 497–516. https://doi. org/10.1128/CMR.16.3.497–516.2003

Bhat, R., Rai, R.V. and Karim, A.A. (2010). Mycotoxins in food and feed: present status and future concerns. Comprehensive Reviews in Food Science and Food Safety, 9(1): 57–81. https://doi. org/10.1111/j.1541-4337.2009.00094.x

Birkinshaw, J.H., Michael, S.E., Bracken, A. and Raistrick, H. (1944). Clinical trial of patulin in the common cold. report of the Patulin Clinical Trials Committee, Medical Research Council. The Lancet, 244 (6316): 373–375.https://doi. org/10.1016/S0140-6736(00)45330-4

Bisht, S.S., Praveen, B., Panda, A., Behera, S., Panda, K.K., Mishra, R. and Patro, S.K. (2011). Comparative study of various mycotoxins against few bacterial test organisms. International Journal of Pharmacy and Pharmaceutical Sciences, 3(SUPPL. 5): 288–291. https://doi. org/10.18579/jpcrkc/2011/10/3/89005

Boruta, T. (2018). Uncovering the repertoire of fungal secondary metabolites: From fleming’s laboratory to the international space station. Bioengineered, 9(1): 12–16. https://doi.org/10.1080/21655979.2017.1341022

Boutibonne, P. (1979). Determination of the antibacterial activity of various mycotoxins using Bacillus thuringiensis (Berliner). Mycopathologia, 67 (1), 45–50.

Boutibonnes, P. (1976). Antibacterial effect of various mycotoxins and fungal metabolites against Bacillus thuringiensis (Berliner) strains sensitive or resistant to aflatoxin B1. Canadian Journal of Microbiology, 22(6), 884–886. https://doi.org/10.1139/m76-127

Boutibonnes, P. (1979). Antibacterial activity of zearalenone. Canadian Journal of Microbiology, 25(3): 421–423. https:// doi.org/10.1139/m79-064

Boutibonnes, P., Auffray, Y., Malherbe, C., Kogbo, W. and Marais, C. (1984). Proprietes antibacteriennes et genotoxiques de 33 mycotoxines. Mycopathologia, 87(1–2): 43–49. https://doi.org/10.1007/BF00436626

Broom, L. (2015). Mycotoxins and the intestine. Animal Nutrition, 1(4): 262–265. https://doi.org/10.1016/j. aninu.2015.11.001

Burel, C., Tanguy, M., Guerre, P., Boilletot, E., Cariolet, R., Queguiner, M.et al. (2013). Effect of Low dose of fumonisins on pig health: Immune Status, Intestinal Microbiota and Sensitivity to Salmonella. Toxins, 5(4), 841–864. https://doi. org/10.3390/toxins5040841

Christiane G-D, Timothy Jenkins, G. S. (2019). Global Mycotoxin Occurrence in Feed. Toxins, 11(375).

Courvalin, P. and Pasteur, I. (2009). Antibiotic Resistance. In Encyclopedia of Microbiology (Third, pp. 193–204).

FDA. (2010). Advisory Levels for Deoxynivalenol (DON) in Finished Wheat Products for Human Consumption and Grains and Grain By-Products used for Animal Feed. U.S. Food and Drug Administration Guidance Document, 20855, 4. Retrieved from http://scholar. google.com /scholar?hl=en&btnG= Search&q = intitle: Guidance + for + Industry + and+ FDA+ : +Advisory + Levels+for + Deoxynivalenol + (+DON+)+in+ Finished + Wheat + Products + for + Human + Consumption+and + Grains+ and+ Grain+ By-Products + used+ for+ Animal + Feed#0

Gallo, A., Giuberti, G., Frisvad, J.C., Bertuzzi, T. and Nielsen, K.F. (2015). Review on mycotoxin issues in ruminants: occurrence in forages, effects of mycotoxin ingestion on health status and animal performance and practical strategies to counteract their negative effects, 3057–3111. https://doi. org/10.3390/toxins7083057

Gaucher, G.M. and Behie, L.A. (1987). Cell immobilization in the production of patulin and penicillin by Penicillium urticae and Penicillium chrysogenum. Methods in Enzymology, 136, 329–342. https://doi.org/10.7868/ s0424857017010029

Grenier, B. and Oswald, I. P. (2011). Mycotoxin co-contamination of food and feed: Meta-analysis of publications describing toxicological interactions. World Mycotoxin Journal, 4(3), 285–313. https://doi.org/10.3920/WMJ2011.1281

Guerre, P. (2020). Mycotoxin and Gut Microbiota Interactions. Toxins, 12(12), 1–33. https://doi.org/10.3390/ toxins12120769

Gunatilaka, A. A. L. (2010). Fungal secondary metabolites. Access Science - The Science Authority, 100063 (1985): 1–5. https://doi.org/doi.org/10.1036/1097- 8542.YB100063

Hassan, Y. I., He, J. W., Lepp, D. and Zhou, T. (2019). Understanding the bacterial response to mycotoxins: The transcriptomic analysis of deoxynivalenol-induced changes in devosia mutans 17-2-e-8. Frontiers in Pharmacology, 10 (November): 1–11. https://doi.org/10.3389/ fphar.2019.01098

He, S., Wang, Q., Li, S., Ran, C., Guo, X., Zhang, Z. and Zhou, Z. (2017). Antibiotic growth promoter olaquindox increases pathogen susceptibility in fish by inducing gut microbiota dysbiosis. Science China Life Sciences, 60(11): 1260–1270. https://doi.org/10.1007/ s11427-016-9072-6

Hong, J, Dai, J., Guan, W., Jin, G., Huang, Z., Zhang, L. and Zhang, Y. (2012). Tachyplesin I induce drug resistance in bacteria in vitro. Journal of Animal and Veterinary Advances, 11: 939–945.

Hong, J., Hu, J. and Ke, F. (2016). Experimental Induction of Bacterial Resistance to the Antimicrobial Peptide Tachyplesin I and Investigation of the Resistance Mechanisms, 60(10): 6067–6075. https://doi.org/10.1128/AAC.00640-16.

Hopkins, J. (1993). The toxicological hazards of patulin. Food and Chemical Toxicology, 31(6), 455–456. https://doi. org/10.1016/S0195-6698(80)80053-9

Kampf, G. (2018). Biocidal agents used for disinfection can enhance antibiotic resistance in gram-negative species. Antibiotics, 7(4). https://doi.org/10.3390/ antibiotics7040110

Knutsen, H.K., Alexander, J., Barregård, L., Bignami, M., Brüschweiler, B. et al. (2017). Risks to human and animal health related to the presence of deoxynivalenol and its acetylated and modified forms in food and feed. EFSA Journal, 15(9). https://doi.org/10.2903/j.efsa.2017.4718

Li, C., Chen, J. and Li, S.C. (2020). Understanding horizontal gene transfer network in human gut microbiota. Gut Pathogens, 12(1): 1–20. https://doi. org/10.1186/s13099-020-00370-9

Liew, W.P.P. and Mohd-Redzwan, S. (2018). Mycotoxin: Its impact on gut health and microbiota. Frontiers in Cellular and Infection Microbiology, 8(FEB). https:// doi.org/10.3389/fcimb.2018.00060

May, H. D., Wu, Q. and Blake, C. K. (2000). Effects of the Fusarium spp. mycotoxins fusaric acid and deoxynivalenol on the growth of Ruminococcus albus and Methano brevibacter ruminantium. Canadian Journal of Microbiology, 46(8): 692–699. https://doi.org/10.1139/ cjm-46-8-692

Mazumder, P. M., Mazumder, R., Mazumder, A. and Sasmal, D. S. (2002). Antimicrobial activity of the mycotoxin citrinin obtained from the fungus Penicillium Citrinum. Ancient Science of Life, 21(3): 191–197. Retrieved from http://www.ncbi.nlm.nih.gov/ pubmed/22557053% 0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3331043

Milanov, D., Ljubojevic, D., Cabarkapa, I. and Aleksic, N. (2016). Impact of antibiotics used as growth promoters on bacterial resistance. Food and Feed Research, 43(2): 83–92. https://doi.org/10.5937/ ffr1602083m

Nešić, K., Habschied, K. and Mastanjević, K. (2021). Possibilities for the Biological Control of Mycotoxins in Food and Feed. Toxins, 13(3): 198. https://doi. org/10.3390/toxins13030198

Neuman, H., Forsythe, P., Uzan, A., Avni, O., Koren, O., Medicine, F., et al. (2018). Antibiotics in early life: dysbiosis and the damage done, (December 2017), 1–11. https://doi.org/10.1093/femsre/ fuy018

Praveena, Y.S.N. and Padmini, P.P.C. (2011). Antibacterial activities of mycotoxins from newly isolated filamentous fungi. International Journal of Plant, Animal and Environmental Sciences, 1(1): 8–13.

Prayle, A., Watson, A., Fortnum, H. and Smyth, A. (2010). Side effects of aminoglycosides on the kidney, ear and balance in cystic fibrosis. Thorax, 65(7): 654–658. https://doi.org/10.1136/ thx.2009.131532

Raistrick, H. (1943). Patulin in the common cold. The Lancet, 241(6227): 1–3. https:// doi.org/10.1016/s0140-6736(00)70684- 2

Roig, M., Meca, G., Marín, R., Ferrer, E. and Mañes, J. (2014). Antibacterial activity of the emerging Fusarium mycotoxins enniatins A, A1, A2, B, B1, and B4 on probiotic microorganisms. Toxicon, 85: 1–4. https://doi.org/10.1016/j. toxicon.2014.04.007

Rosenberg, C.R., Fang, X. and Allison, K.R. (2020). Potentiating aminoglycoside antibiotics to reduce their toxic side effects. PLoS ONE, 15(9 September): 1–17. https://doi.org/10.1371/journal. pone.0237948

Ruiz, J.A., Bernar, E.M. and Jung, K. (2015). Production of siderophores increases resistance to fusaric acid in Pseudomonas protegens Pf-5. PLoS ONE, 10(1): 1–16. https://doi.org/10.1371/journal. pone.0117040

Sanders, C.C. (2001). Mechanisms responsible for cross-resistance and dichotomous resistance among the quinolones. Clinical Infectious Diseases, 32(Suppl. 1). https://doi.org/10.1086/319369

Sanders, C.C, Sanders, W.E., Goering, R.V, Werner, V., Pharmaceuticals, M. and Haven, W. (1984). Selection of multiple antibiotic resistance by quinolones, 1- lactams, and aminoglycosides with special reference to cross- resistance between unrelated drug classes. Antimicrobial Agents Chemotherapy, 26(6): 797–801.

SCENIHR (2009). Scientific Committee on Emerging and Newly-Identified Health Risks. Assessment of the Antibiotic Resistance Effects of Biocides. Environment, (June), 68. Retrieved from http://ec.europa.eu/health/ph_risk/risk_ en.htm

Shier, W.T. (2011). On the origin of antibiotics and mycotoxins, 30 (December 2010), 6–30. https://doi.org/10.3109/15569543.2011.550862

Shterzer, N. and Mizrahi, I. (2015). The animal gut as a melting pot for horizontal gene transfer. Canadian Journal of Microbiology, 61, 603–605. https://doi. org/10.3390/life4020217

Slifierz, M.J., Friendship, R.M. and Scott, J. (2015). Methicillin-resistant Staphylococcus aureus in Commercial swine herds is associated with disinfectant and zinc usage. Applied and Environmental Microbiology, 81(8): 2690–2695. https://doi.org/10.1128/ AEM.00036-15

Spraker, J.E., Sanchez, L.M., Lowe, T.M., Dorrestein, P.C. and Keller, N.P. (2016). Ralstonia solanacearum lipopeptide induces chlamydospore development in fungi and facilitates bacterial entry into fungal tissues. ISME Journal, 10(9), 2317–2330. https://doi.org/10.1038/ ismej.2016.32

Vanhoutte, I., Audenaert, K. and De Gelder, L. (2016). Biodegradation of mycotoxins: Tales from known and unexplored worlds. Frontiers in Microbiology, 7(APR): 1–20. https://doi.org/10.3389/ fmicb.2016.00561

Venkatesh, N. and Keller, N.P. (2019). Mycotoxins in conversation with bacteria and fungi. Frontiers in Microbiology, 10, 403. https://doi.org/10.3389/ fmicb.2019.00403

Vidovic, N. and Vidovic, S. (2020). Antimicrobial resistance and food animals: Influence of livestock environment on the emergence and dissemination of antimicrobial resistance. Antibiotics, 9(2). https://doi. org/10.3390/antibiotics9020052

Waché, Y.J., Valat, C., Postollec, G., Bougeard, S., Burel, C., Oswald, I.P. and Fravalo, P. (2009). Impact of deoxynivalenol on the intestinal microflora of pigs. International Journal of Molecular Sciences, 10(1): 1–17. https://doi. org/10.3390/ijms10010001

Wistrand-Yuen, E., Knopp, M., Hjort, K., Koskiniemi, S., Berg, O.G. and Andersson, D.I. (2018). Evolution of high-level resistance during low- level antibiotic exposure. Nature Communications, 9(1). https://doi. org/10.1038/s41467-018-04059-1

Downloads

Submitted

29-08-2022

Published

31-10-2025

How to Cite

Prathap Kumar Kothapalli, M.N. Balakrishna Nair, & N. Punniyamurthy. (2025). MYCOTOXIN INDUCED ANTIBIOTIC RESISTANCE, AN UNSUSPECTED PUBLIC HEALTH IMPACT: A PERSPECTIVE REVIEW. Indian Journal of Veterinary and Animal Sciences Research, 50(4), 1-15. https://doi.org/10.56093/ijvasr.v50i4.127556
Citation