In Vitro Activity of Nisin A Against Staphylococci Isolated from Periprosthetic Joint Infection
Abstract
1. Introduction
2. Results
3. Discussion
4. Materials and Methods
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
PJI | Periprosthetic joint infection |
MRSA | Methicillin-resistant Staphylococcus aureus |
MSSA | Methicillin-susceptible Staphylococcus aureus |
MRSE | Methicillin-resistant Staphylococcus epidermidis |
MSSE | Methicillin-susceptible Staphylococcus epidermidis |
CaMHB | Cation-adjusted Mueller Hinton broth |
MIC | Minimum inhibitory concentration |
MBBC | Minimum biofilm bactericidal concentration |
PBS | Phosphate-buffered saline |
FIC | Fractional inhibitory concentration |
References
- Patel, R. Periprosthetic joint infection. N. Engl. J. Med. 2023, 388, 251–262. [Google Scholar] [CrossRef]
- Masters, E.A.; Ricciardi, B.F.; Bentley, K.L.d.M.; Moriarty, T.F.; Schwarz, E.M.; Muthukrishnan, G. Skeletal infections: Microbial pathogenesis, immunity and clinical management. Nat. Rev. Microbiol. 2022, 20, 385–400. [Google Scholar] [CrossRef]
- Ho, C.S.; Wong, C.T.H.; Aung, T.T.; Lakshminarayanan, R.; Mehta, J.S.; Rauz, S.; McNally, A.; Kintses, B.; Peacock, S.J.; de la Fuente-Nunez, C.; et al. Antimicrobial resistance: A concise update. Lancet Microbe 2025, 6, 100947. [Google Scholar] [CrossRef] [PubMed]
- Shin, J.M.; Gwak, J.W.; Kamarajan, P.; Fenno, J.C.; Rickard, A.H.; Kapila, Y.L. Biomedical applications of nisin. J. Appl. Microbiol. 2016, 120, 1449–1465. [Google Scholar] [CrossRef] [PubMed]
- Okuda, K.-i.; Zendo, T.; Sugimoto, S.; Iwase, T.; Tajima, A.; Yamada, S.; Sonomoto, K.; Mizunoe, Y. Effects of bacteriocins on methicillin-resistant Staphylococcus aureus biofilm. Antimicrob. Agents Chemother. 2013, 57, 5572–5579. [Google Scholar] [CrossRef] [PubMed]
- Angelopoulou, A.; Field, D.; Pérez-Ibarreche, M.; Warda, A.K.; Hill, C.; Ross, R.P. Vancomycin and nisin A are effective against biofilms of multi-drug resistant Staphylococcus aureus isolates from human milk. PLoS ONE 2020, 15, e0233284. [Google Scholar] [CrossRef] [PubMed]
- Dosler, S.; Gerceker, A.A. In vitro activities of nisin alone or in combination with vancomycin and ciprofloxacin against methicillin-resistant and methicillin-susceptible Staphylococcus aureus strains. Chemotherapy 2012, 57, 511–516. [Google Scholar] [CrossRef] [PubMed]
- Godoy-Santos, F.; Pitts, B.; Stewart, P.S.; Mantovani, H.C. Nisin penetration and efficacy against Staphylococcus aureus biofilms under continuous-flow conditions. Microbiology 2019, 165, 761–771. [Google Scholar] [CrossRef] [PubMed]
- Jensen, C.; Li, H.; Vestergaard, M.; Dalsgaard, A.; Frees, D.; Leisner, J.J. Nisin damages the septal membrane and triggers DNA condensation in methicillin-resistant Staphylococcus aureus. Front. Microbiol. 2020, 11, 1007. [Google Scholar] [CrossRef] [PubMed]
- Kitazaki, K.; Koga, S.; Nagatoshi, K.; Kuwano, K.; Zendo, T.; Nakayama, J.; Sonomoto, K.; Ano, H.; Katamoto, H. In vitro synergistic activities of cefazolin and nisin A against mastitis pathogens. J. Vet. Med. Sci. 2017, 79, 1472–1479. [Google Scholar] [CrossRef] [PubMed]
- Field, D.; O’ Connor, R.; Cotter, P.D.; Ross, R.P.; Hill, C. In vitro activities of nisin and nisin derivatives alone and in combination with antibiotics against Staphylococcus biofilms. Front. Microbiol. 2016, 7, 508. [Google Scholar] [CrossRef] [PubMed]
- Brothers, K.M.; Parker, D.M.; Taguchi, M.; Ma, D.; Mandell, J.B.; Thurlow, L.L.; Byrapogu, V.C.; Urish, K.L. Dose optimization in surgical prophylaxis: Sub-inhibitory dosing of vancomycin increases rates of biofilm formation and the rates of surgical site infection. Sci. Rep. 2023, 13, 4593. [Google Scholar] [CrossRef] [PubMed]
- Cargill, J.S.; Upton, M. Low concentrations of vancomycin stimulate biofilm formation in some clinical isolates of Staphylococcus epidermidis. J. Clin. Path. 2009, 62, 1112–1116. [Google Scholar] [CrossRef] [PubMed]
- Kim, C.K.; Karau, M.J.; Greenwood-Quaintance, K.E.; Tilahun, A.Y.; David, C.S.; Mandrekar, J.N.; Patel, R.; Rajagopalan, G. Superantigens in Staphylococcus aureus isolated from prosthetic joint infection. Diagn. Microbiol. Infect. Dis. 2015, 81, 201–207. [Google Scholar] [CrossRef] [PubMed]
- Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing, 33rd ed.; CLSI Supplement 100; Clinical and Laboratory Standards Institute: Wayne, PA, USA, 2023; ISBN 978-1-68440-171-0. [Google Scholar]
- Clinical and Laboratory Standards Institute. Dilution Antimicrobial Susceptibility Tests For Bacteria That Grow Aerobically, 12th ed.; CLSI Standard M07; Clinical and Laboratory Standards Institute: Wayne, PA, USA, 2024; ISBN 978-1-68440-227-7. [Google Scholar]
- Ceri, H.; Olson, M.E.; Stremick, C.; Read, R.; Morck, D.; Buret, A. The Calgary Biofilm Device: New technology for rapid determination of antibiotic susceptibilities of bacterial biofilms. J. Clin. Microbiol. 1999, 37, 1771–1776. [Google Scholar] [CrossRef] [PubMed]
- Fisher, C.R.; Schmidt-Malan, S.M.; Ma, Z.; Yuan, Y.; He, S.; Patel, R. In vitro activity of TNP-2092 against periprosthetic joint infection–associated staphylococci. Diagn. Microbiol. Infect. Dis. 2020, 97, 115040. [Google Scholar] [CrossRef] [PubMed]
- Washington, J.A. Laboratory Procedures in Clinical Microbiology, 2nd ed.; Springer Science & Business Media: New York, NY, USA, 1985; pp. 739–741. [Google Scholar]
- White, R.L.; Burgess, D.S.; Manduru, M.; Bosso, J.A. Comparison of three different in vitro methods of detecting synergy: Time-kill, checkerboard, and E test. Antimicrob. Agents Chemother. 1996, 40, 1914–1918. [Google Scholar] [CrossRef] [PubMed]
MIC (µg/mL) | MIC50 | MIC90 | ||||||||||
≤0.5 | 1 | 2 | 4 | 8 | 16 | 32 | 64 | 128 | 256 | |||
MRSA | 7 (26.9) | 15 (57.7) | 4 (15.4) | 4 | 8 | |||||||
MSSA | 11 (37.9) | 17 (58.6) | 1 (3.5) | 4 | 4 | |||||||
MRSE | 4 (14.8) | 17 (63) | 5 (18.5) | 1 (3.7) | 2 | 4 | ||||||
MSSE | 1 (9.1) | 7 (63.6) | 3 (27.3) | 2 | 4 | |||||||
S. lug | 2 (28.6) | 3 (42.8) | 2 (28.6) | NA | NA | |||||||
Other | 4 (66.7) | 2 (33.3) | NA | NA | ||||||||
MBIC (µg/mL) | MBIC50 | MBIC90 | ||||||||||
≤0.5 | 1 | 2 | 4 | 8 | 16 | 32 | 64 | 128 | 256 | |||
MRSA | 1 (3.8) | 9 (34.6) | 14 (53.8) | 2 (7.7) | 4 | 4 | ||||||
MSSA | 10 (34.5) | 10 (34.5) | 8 (27.5) | 1 (3.5) | 2 | 4 | ||||||
MRSE | 2 (7.4) | 8 (29.7) | 13 (48.1) | 2 (7.4) | 2 (7.4) | 2 | 4 | |||||
MSSE | 1 (9.1) | 5 (45.4) | 4 (36.4) | 1 (9.1) | 2 | 4 | ||||||
S. lug | 2 (28.6) | 5 (74.1) | NA | NA | ||||||||
Other | 3 (50) | 2 (33.3) | 1 (16.7) | NA | NA | |||||||
MBBC (µg/mL) | MBBC50 | MBBC90 | ||||||||||
≤0.5 | 1 | 2 | 4 | 8 | 16 | 32 | 64 | 128 | 256 | |||
MRSA | 1 (3.8) | 6 (23.1) | 10 (38.5) | 5 (19.2) | 4 (15.4) | 64 | 256 | |||||
MSSA | 1 (3.5) | 3 (10.3) | 18 (62.1) | 5 (17.2) | 1 (3.5) | 1 (3.5) | 32 | 64 | ||||
MRSE | 2 (7.4) | 7 (25.9) | 13 (48.1) | 5 (18.5) | 64 | 128 | ||||||
MSSE | 2 (18.2) | 6 (54.5) | 2 (18.2) | 1 (9.1) | 64 | 128 | ||||||
S. lug | 2 (28.6) | 2 (28.6) | 2 (28.6) | 1 (14.2) | NA | NA | ||||||
Other | 1 (16.7) | 3 (50) | 2 (33.3) | NA | NA |
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Karau, M.J.; Koscianski, C.A.; Badley, A.D.; Bedard, N.A.; Zinckgraf, J.W.; Patel, R. In Vitro Activity of Nisin A Against Staphylococci Isolated from Periprosthetic Joint Infection. Antibiotics 2025, 14, 515. https://doi.org/10.3390/antibiotics14050515
Karau MJ, Koscianski CA, Badley AD, Bedard NA, Zinckgraf JW, Patel R. In Vitro Activity of Nisin A Against Staphylococci Isolated from Periprosthetic Joint Infection. Antibiotics. 2025; 14(5):515. https://doi.org/10.3390/antibiotics14050515
Chicago/Turabian StyleKarau, Melissa J., Christina A. Koscianski, Andrew D. Badley, Nicholas A. Bedard, John W. Zinckgraf, and Robin Patel. 2025. "In Vitro Activity of Nisin A Against Staphylococci Isolated from Periprosthetic Joint Infection" Antibiotics 14, no. 5: 515. https://doi.org/10.3390/antibiotics14050515
APA StyleKarau, M. J., Koscianski, C. A., Badley, A. D., Bedard, N. A., Zinckgraf, J. W., & Patel, R. (2025). In Vitro Activity of Nisin A Against Staphylococci Isolated from Periprosthetic Joint Infection. Antibiotics, 14(5), 515. https://doi.org/10.3390/antibiotics14050515