Abstract
There is an imperative need to discover novel antimicrobials and anti-infective agents and build up innovative strategies to combat multidrug-resistant Salmonella. In this context, we had earlier confirmed that nisin has the potential to act in conjunction with β-lactams against murine salmonellosis using standard strain. However, evaluation of efficacy of these combinations against clinical isolates of Salmonella could be the next key step to confirm the value added potential of this peptide. The present study was therefore planned to validate the synergistic effects of nisin–β-lactams combinations against clinical isolates of Salmonella enterica serovar Typhi. MICs of the selected β-lactams, EDTA and nisin were determined by micro and macro broth dilution assays. In-vitro synergism between the agents was evaluated by fractional inhibitory concentration (FIC) index (checkerboard test) and time-kill assay. All the tested combinations showed synergy against the tested clinical strains except three, as evident by FIC index (checkerboard test) and time-kill assay. Especially, nisin–ceftriaxone and nisin–cefotaxime combinations demonstrated excellent synergistic activity. In view of the encouraging results obtained from the previous and present study, further studies need to be carried out using large number of strains from different regions to take into account the clinical variability of the strains. Though it is a simple study but highlights an important point about the possibility of using the said combination while making strategies to develop newer formulations.
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References
Tsolis, R. M ., Xavier, M. N ., Santos, R. L . & Bäumler, A. J . How to become a top model: impact of animal experimentation on human Salmonella disease research. Infect. Immun. 79, 1806–1814 (2011).
Siddiqui, F. J ., Rabbani, F ., Hasan, R ., Nizami, S. Q . & Bhutta, Z. A . Typhoid fever in children: some epidemiological considerations from Karachi, Pakistan. Int. J. Infect Dis. 10, 215–222 (2006).
Ochiai, R. L ., Acosta, C. J . & Danovaro-Holliday, M . A study of typhoid fever in five Asian countries: disease burden and implications for controls. Bull. World Health Organ. 86, 260–268 (2008).
Threlfall, E. J ., Skinner, J. A . & Ward, L. R . Detection of decreased in vitro susceptibility to ciprofloxacin in Salmonella enterica serotypes typhi and paratyphi A. J. Antimicrob. Chemother. 48, 740–741 (2001).
Joerger, R. D . Alternatives to antibiotics: bacteriocins, antimicrobial peptides and bacteriophages. Poult. Sci. 82, 640–647 (2003).
Birosova, L . & Mikulasova, M . Development of triclosan and antibiotic resistance in Salmonella enterica serovar Typhimurium. J. Med. Microbiol. 58, 436–441 (2009).
Singh, A. P ., Prabha, V . & Rishi, P . Value addition in the efficacy of conventional antibiotics by nisin against Salmonella. PLoS ONE 8, e76844 (2013).
Field, D . et al. Bioengineered nisin A derivatives with enhanced activity against both Gram positive and Gram negative pathogens. PLoS ONE 7, e46884 (2012).
Boziaris, I. S . & Adams, M. R . Effect of chelators and nisin produced in situ on inhibition and inactivation of Gram negatives. Int. J. Food Microbiol. 53, 105–113 (1999).
Cassone, M . & Otvos, L. Jr . Synergy among antibacterial peptides and between peptides and small-molecule antibiotics. Expert Rev. Anti Infect. Ther. 8, 703–716 (2010).
Bauer, A. W ., Kirby, W. M ., Sherris, J. C . & Turck, M . Antimicrobial susceptibility testing by a standardized single disc method. Am. J. Clin. Pathol. 45, 493–496 (1966).
Clinical and Laboratory Standards Institute M100-S20. Performance Standards for Antimicrobial Susceptibility Testing: 20th Informational Supplement, CLSI, Wayne, PA, USA (2010).
Rishi, P ., Preet, S ., Bharrhan, S . & Verma, I . In-vitro and in-vivo synergistic effects of cryptdin 2 and ampicillin against Salmonella. Antimicrob. Agents Chemother. 55, 4176–4182 (2011).
Chuang, C . et al. Surveillance of antimicrobial resistance of Salmonella enterica serotype Typhi in seven Asian countries. Epidemiol. Infect. 137, 266–269 (2009).
Maskey, A. P . et al. Emerging trends in enteric fever in Nepal: 9124 cases confirmed by blood culture 1993–2003. Trans. R. Soc. Trop. Med. Hyg. 102, 91–95 (2008).
Chalon, M. C ., Acuña, L ., Morero, R. D ., Minahk, C. J . & Bellomio, A . Membrane-active bacteriocins to control Salmonella in foods: are they the definite hurdle? Food Res. Int. 45, 735–744 (2012).
Majtan, J ., Majtanova, L . & Majtan, V . Increasing trend of resistance to nalidixic acid and emerging ceftriaxone and ciprofloxacin resistance in Salmonella enterica serovar Typhimurium in Slovakia, 2005 to 2009. Diagn. Microbiol. Infect. Dis. 68, 86–88 (2010).
Ye, J . et al. Analysis of pSC138, the multidrug resistance plasmid of Salmonella enterica serotype Choleraesuis SC-B67. Plasmid 65, 132–140 (2011).
Cotter, P. D ., Ross, R. P . & Hill, C . Bacteriocins-a viable alternative to antibiotics? Nat. Rev. Microbiol. 11, 95–105 (2013).
Freeman, M. F . et al. Metagenome mining reveals polytheonamides as posttranslationally modified ribosomal peptides. Science 338, 387–390 (2012).
Ruhr, E . & Sahl, H. G . Mode of action of the peptide antibiotic nisin and influence on the membrane potential of whole cells and on cytoplasmic and artificial membrane vesicles. Antimicrob. Agents Chemother. 27, 841–845 (1985).
Gut, I. M ., Blanke, S. R . & van der Donk, W. A . Mechanism of inhibition of Bacillus anthracis spore outgrowth by the lantibiotic nisin. ACS Chem. Biol. 6, 744–752 (2011).
Kohanski, M. A ., Dwyer, D. J . & Collins, J. J . How antibiotics kill bacteria: from targets to networks. Nat. Rev. Microbiol. 8, 423–435 (2010).
Kohanski, M. A ., Dwyer, D. J ., Hayete, B ., Lawrence, C. A . & Collins, J. J . A common mechanism of cellular death induced by bactericidal antibiotics. Cell 130, 797–810 (2007).
Acknowledgements
We acknowledge Dr Jagadish Chander and Dr Varsha Gupta, Government Medical College and Hospital (GMCH), Chandigarh, for providing clinical isolates to carry out this work.
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Rishi, P., Preet Singh, A., Garg, N. et al. Evaluation of nisin–β-lactam antibiotics against clinical strains of Salmonella enterica serovar Typhi. J Antibiot 67, 807–811 (2014). https://doi.org/10.1038/ja.2014.75
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DOI: https://doi.org/10.1038/ja.2014.75
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