Nisin activity against methicillin-resistant and methicillin-sensitive Staphylococcus aureus and risk of resistance acquisition




Antibiotic resistance; Antimicrobial activity; Bacteriocin; Staphylococcus aureus.


The objective of this study was to analyze the antimicrobial effect of nisin against MRSA (Methicillin-Resistant Staphylococcus aureus) and MSSA (Methicillin-Sensitive Staphylococcus aureus), and at the same time examine the possibility of the bacteria to develope nisin resistance. The antimicrobial susceptibility of the strains was tested using the agar diffusion and/or microdilution methods. To select nisin-resistant strains, bacteria were grown consecutively at sublethal concentrations of the bacteriocin. Nisin showed bactericidal activity against most of the tested strains. MRSA required higher doses of bacteriocin compared to MSSA both for inhibition and cell death. However, transfers in the presence of nisin could completely eliminate nisin activity with an increase in minimal inhibitory concentration value of up to 250 times. Nisin-resistance could be maintained in MRSA and MSSA even in the absence of the bacteriocin. Nisin resistance affected antibiotic susceptibility of both MRSA and MSSA to mainly Cefoxitin, Oxacillin, and Erythromycin. These results indicate that nisin-resistance is a complex trait among MSSA and MRSA and must be elucidated before the therapeutic recommendation of nisin to treat infections caused by these bacterial species.


Alves, F. C. B., Albano, M., Andrade, B. F. M. T., Chechi, J. L., Pereira, A. F. M., Furlanetto, A., … Fernandes, A. (2020). Comparative Proteomics of Methicillin-Resistant Staphylococcus aureus Subjected to Synergistic Effects of the Lantibiotic Nisin and Oxacillin. Microbial Drug Resistance, 26(3), 179–189.

Bauer, P. R., & Sampathkumar, P. (2017). Methicillin-resistant Staphylococcus aureus infection in ICU: What is the best prevention strategy? Critical Care Medicine, 45 (8), 1413–1414.

Bhattacharya, R., Gupta, A.M., Mitra, S., Mandal, S., Biswas, S.R. (2021). A natural food preservative peptide nisin can interact with the SARS-CoV-2 spike protein receptor human ACE2. Virology, 2 (552), 107-111.

Blake, K. L., Randall, C. P., & O’Neill, A. J. (2011). In vitro studies indicate a high resistance potential for the lantibiotic nisin in Staphylococcus aureus and define a genetic basis for nisin resistance. Antimicrobial Agents and Chemotherapy, 55(5), 2362–2368.

Cafiso, V., Stracquadanio, S., Lo Verde, F., De Guidi, I., Zega, A., Pigola, G., & Stefani, S. (2020). Genomic and Long-Term Transcriptomic Imprints Related to the Daptomycin Mechanism of Action Occurring in Daptomycin- and Methicillin-Resistant Staphylococcus aureus Under Daptomycin Exposure. Frontiers in Microbiology, 11, 1893.

Calfee, D. P. (2012, August). Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, and other Gram-positives in healthcare. Current Opinion in Infectious Diseases, 25 (4), 385–394.

Castro, A., Palhau, C., Cunha, S., Camarinha, S., Silva, J., & Teixeira, P. (2017). Virulence and resistance profile of Staphylococcus aureus isolated from food. Acta Alimentaria, 46(2), 231–237.

Ceballos, S., Aspiroz, C., Ruiz-Ripa, L., Azcona-Gutierrez, J.M., López-Cerero, L., López-Calleja, A.I., Álvarez, L., Gomáriz, M., Fernández, M., Torres, C. (2019). Multicenter study of clinical non-beta-lactam-antibiotic susceptible MRSA strains: Genetic lineages and Panton-Valentine leukocidin (PVL) production. Enfermedades Infecciosas y Microbiología Clínica, 37(8):509-513.

Center for Disease Control and Prevention. (2015). Morbidity And Mortality Weekly Report. Retrieved September 6, 2019, from

Ceotto-Vigoder, H., Marques, S. L. S., Santos, I. N. S., Alves, M. D. B., Barrias, E. S., Potter, A., … Bastos, M. C. F. (2016). Nisin and lysostaphin activity against preformed biofilm of Staphylococcus aureus involved in bovine mastitis. Journal of Applied Microbiology, 121(1), 101–114.

Cleveland, J., Montville, T. J., Nes, I. F., & Chikindas, M. L. (2001). Bacteriocins: Safe, natural antimicrobials for food preservation. International Journal of Food Microbiology, Vol. 71 (1), 1–20.

Clinical and Laboratory Standarts Institute. n.d. (2019). “Performance Standards for Antimicrobial Susceptibility Testing. 27th Ed. CLSI Supplement M100 .

Cotter, P. D., Ross, R. P., & Hill, C. (2013). Bacteriocins-a viable alternative to antibiotics? Nature Reviews Microbiology, 11 (2), 95–105.

Dosler, S., & Gerceker, A. A. (2012). In vitro activities of nisin alone or in combination with vancomycin and ciprofloxacin against methicillin-resistant and methicillin-susceptible Staphylococcus aureus strains. Chemotherapy, 57(6), 511–516.

Draper, L. A., Cotter, P. D., Hill, C., & Ross, R. P. (2015). Lantibiotic Resistance. Microbiology and Molecular Biology Reviews, 79(2), 171–191.

Du, H., Zhou, L., Lu, Z., Bie, X., Zhao, H., Niu, Y. D., & Lu, F. (2020). Transcriptomic and proteomic profiling response of methicillin-resistant Staphylococcus aureus (MRSA) to a novel bacteriocin, plantaricin GZ1-27 and its inhibition of biofilm formation. Applied Microbiology and Biotechnology, 104(18), 7957–7970.

Dufour, P., Gillet, Y., le Bes, M., Lina, G., ois Vandenesch, F., Floret, D., … Richet, H. (2002). Community-Acquired Methicillin-Resistant Staphylococcus aureus Infections in France: Emergence of a Single Clone That Produces Panton-Valentine Leukocidin. Clinical Infectious Disease, 35(7):819-24.

Field, D., Cotter, P. D., Hill, C., & Ross, R. P. (2015). Bioengineering lantibiotics for therapeutic success. Frontiers in Microbiology, 27 (6), 1363.

Gedarawatte, S. T. G., Ravensdale, J. T., Al-Salami, H., Dykes, G. A., & Coorey, R. (2021). Antimicrobial efficacy of nisin-loaded bacterial cellulose nanocrystals against selected meat spoilage lactic acid bacteria. Carbohydrate Polymers, 251, 117096.

Hanchi, H., Hammami, R., Gingras, H., Kourda, R., Bergeron, M. G., Ben Hamida, J., … Fliss, I. (2017). Inhibition of MRSA and of Clostridium difficile by durancin 61A: Synergy with bacteriocins and antibiotics. Future Microbiology, 12(3), 205–212.

Hayes, K., Cotter, L., & O’Halloran, F. (2019). In vitro synergistic activity of erythromycin and nisin against clinical Group B Streptococcus isolates. Journal of Applied Microbiology, 127(5), 1381–1390.

Heunis, T. D. J., Smith, C., & Dicks, L. M. T. (2013). Evaluation of a nisin-eluting nanofiber scaffold to treat Staphylococcus aureus-induced skin infections in mice. Antimicrobial Agents and Chemotherapy, 57(8), 3928–3935.

Hiramatsu, K., Suzuki, E., Takayama, H., Katayama, Y., & Yokota, T. (1990). Role of penicillinase plasmids in the stability of the mecA gene in methicillin-resistant Staphylococcus aureus. Antimicrobial Agents and Chemotherapy, 34(4), 600–604.

Hiron, A., Falord, M., Valle, J., Débarbouillé, M., & Msadek, T. (2011). Bacitracin and nisin resistance in Staphylococcus aureus: A novel pathway involving the BraS/BraR two-component system (SA2417/SA2418) and both the BraD/BraE and VraD/VraE ABC transporters. Molecular Microbiology, 81(3), 602–622.

Hosseini, S. S., Goudarzi, H., Ghalavand, Z., Hajikhani, B., Rafeieiatani, Z., & Hakemi-Vala, M. (2020). Anti-proliferative effects of cell wall, cytoplasmic extract of Lactococcus lactis and nisin through down-regulation of cyclin d1 on sw480 colorectal cancer cell line. Iranian Journal of Microbiology, 12(5), 424–430.

Jensen, C., Li, H., Vestergaard, M., Dalsgaard, A., Frees, D., & Leisner, J. J. (2020). Nisin Damages the Septal Membrane and Triggers DNA Condensation in Methicillin-Resistant Staphylococcus aureus. Frontiers in Microbiology, 11 (1007), 1–8.

Kang, J., Wiedmann, M., Boor, K. J., & Bergholz, T. M. (2015). VirR-mediated resistance of Listeria monocytogenes against food antimicrobials and cross-protection induced by exposure to organic acid salts. Applied and Environmental Microbiology, 81(13), 4553–4562.

Kateete, D. P., Bwanga, F., Seni, J., Mayanja, R., Kigozi, E., Mujuni, B., … Joloba, M. L. (2019). CA-MRSA and HA-MRSA coexist in community and hospital settings in Uganda. Antimicrobial Resistance and Infection Control, 8(1), 1–9.

Kaur, G., Singh, T. P., Malik, R. K., Bhardwaj, A., & De, S. (2014). Antibacterial efficacy of nisin, pediocin 34 and enterocin FH99 against L. monocytogenes, E. faecium and E. faecalis and bacteriocin cross resistance and antibiotic susceptibility of their bacteriocin resistant variants. Journal of Food Science and Technology, 51(2), 233–244.

Kranjec, C., Ovchinnikov, K. V., Grønseth, T., Ebineshan, K., Srikantam, A., & Diep, D. B. (2020). A bacteriocin-based antimicrobial formulation to effectively disrupt the cell viability of methicillin-resistant Staphylococcus aureus (MRSA) biofilms. Npj Biofilms and Microbiomes, 6(1), 1–13.

Lakhundi, S., & Zhang, K. (2018). Methicillin-Resistant Staphylococcus aureus: Molecular Characterization, Evolution, and Epidemiology. Clinical Microbiology Reviews, 31(4), 1–103.

Lee, N. K., Jin Han, E., Jun Han, K., & Paik, H. D. (2013). Antimicrobial effect of bacteriocin KU24 produced by lactococcus lactis KU24 against methicillin-Resistant Staphylococcus aureus. Journal of Food Science, 78(3), 465–469.

Lozano, C., Fernández-Fernández, R., Ruiz-Ripa, L., Gómez, P., Zarazaga, M., & Torres, C. (2020). Human mecC-carrying MRSA: Clinical implications and risk factors. Microorganisms, 8(10), 1–20.

Mantovani, H. C., & Russell, J. B. (2001). Nisin Resistance of Streptococcus bovis. APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 67(2), 808–813.

Martínez, B., & Rodríguez, A. (2005). Antimicrobial susceptibility of nisin resistant Listeria monocytogenes of dairy origin. FEMS Microbiology Letters, 252(1), 67–72.

Masias, E., Dupuy, F. G., da Silva Sanches, P. R., Farizano, J. V., Cilli, E., Bellomio, A., … Minahk, C. (2017). Impairment of the class IIa bacteriocin receptor function and membrane structural changes are associated to enterocin CRL35 high resistance in Listeria monocytogenes. Biochimica et Biophysica Acta - General Subjects, 1861(7), 1770–1776.

Okuda, K. I., Zendo, T., Sugimoto, S., Iwase, T., Tajima, A., Yamada, S., … Mizunoe, Y. (2013). Effects of bacteriocins on methicillin-resistant Staphylococcus aureus biofilm. Antimicrobial Agents and Chemotherapy, 57(11), 5572–5579.

Pader, V., & Edwards, A. M. (2017). Daptomycin: New insights into an antibiotic of last resort. Future Microbiology, 12, 461–464.

Piper, C., Draper, L. A., Cotter, P. D., Ross, R. P., & Hill, C. (2009). A comparison of the activities of lacticin 3147 and nisin against drug-resistant Staphylococcus aureus and Enterococcus species. Journal of Antimicrobial Chemotherapy, 64(3), 546–551.

Punjabi, C., Madaline, T., Gendlina, I., Chen, V., Nori, P., & Pirofski, L. A. (2020). Prevalence of methicillin-resistant

Staphylococcus aureus (MRSA) in respiratory cultures and diagnostic performance of the MRSA nasal polymerase chain reaction (PCR) in patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia. Infection Control & Hospital Epidemiology,

Saha, S., Das, A., Debnath, A., Begam, S., Sen, S., Majumdar, S., & Sil, S. K. (2017). Increased ROS Generation: Implication in Antibacterial Activity of Evolvulus nummularius against Multidrug Resistant Gram Negative Bacterial Strains. International Journal of Current Microbiology and Applied Sciences 6(1), 100–107.

Sharifipour, E., Shams, S., Esmkhani, M., Khodadadi, J., Fotouhi-Ardakani, R., Koohpaei, A., … Ej Golzari, S. (2020). Evaluation of bacterial co-infections of the respiratory tract in COVID-19 patients admitted to ICU. BMC Infectious Diseases, 20(1), 1–7.

Shin, J. M., Gwak, J. W., Kamarajan, P., Fenno, J. C., Rickard, A. H., & Kapila, Y. L. (2016). Biomedical applications of nisin. Journal of Applied Microbiology, 120, 1449–1465.

Shokri, D., Zaghian, S., Khodabakhsh, F., Fazeli, H., Mobasherizadeh, S., & Ataei, B. (2014). Antimicrobial activity of a UV-stable bacteriocin-like inhibitory substance (BLIS) produced by Enterococcus faecium strain DSH20 against vancomycin-resistant Enterococcus (VRE) strains. Journal of Microbiology, Immunology, and Infection, 47(5), 371–376.

Smith, M. K., Draper, L. A., Hazelhoff, P. J., Cotter, P. D., Ross, R. P., & Hill, C. (2016). A bioengineered nisin derivative, M21A, in combination with food grade additives eradicates biofilms of Listeria monocytogenes. Frontiers in Microbiology, 7(1939), 1–11.

Togneri, A. M., Podestá, L. B., Pérez, M. P., & Santiso, G. M. (2017). Study of Staphylococcus aureus infections in a general acute care hospital (2002-2013). Revista Argentina de Microbiologia, 49(1), 24–31.

Vivas, R., Barbosa, A. A. T., Dolabela, S. S., & Jain, S. (2019). Multidrug-Resistant Bacteria and Alternative Methods to Control Them: An Overview. Microbial Drug Resistance, 25(6), 890–908.

Vuong, C., Yeh, A. J., Cheung, G. Y. C., & Otto, M. (2016, January 2). Investigational drugs to treat methicillin-resistant Staphylococcus aureus. Expert Opinion on Investigational Drugs, Vol. 25, pp. 73–93.

Yang, S. C., Lin, C. H., Sung, C. T., & Fang, J. Y. (2014). Antibacterial activities of bacteriocins: Application in foods and pharmaceuticals. Frontiers in Microbiology, 5, 241.




How to Cite

SILVA, C. M. R. da .; ALBUQUERQUE , W. da S. .; OLIVEIRA , J. N. A. de .; CARNEIRO , M. R. P. .; JAIN , S.; DOLABELLA , S. S. .; BARBOSA, A. A. T. . Nisin activity against methicillin-resistant and methicillin-sensitive Staphylococcus aureus and risk of resistance acquisition. Research, Society and Development, [S. l.], v. 10, n. 7, p. e4610716178, 2021. DOI: 10.33448/rsd-v10i7.16178. Disponível em: Acesso em: 24 sep. 2023.



Agrarian and Biological Sciences