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In Vitro Activities of Nisin and Nisin Derivatives Alone and In Combination with Antibiotics against Staphylococcus Biofilms
Field, Des ; O'Connor, Rory ; Cotter, Paul D. ; Ross, R Paul ; Hill, Colin
Field, Des
O'Connor, Rory
Cotter, Paul D.
Ross, R Paul
Hill, Colin
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18/04/2016
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fmicb-07-00508.pdf
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Field D, O’ Connor R, Cotter PD, Ross RP and Hill C (2016) In Vitro Activities of Nisin and Nisin Derivatives Alone and In Combination with Antibiotics against Staphylococcus Biofilms. Front. Microbiol. 7:508. doi: 10.3389/fmicb.2016.00508
Abstract
The development and spread of pathogenic bacteria that are resistant to the existing
catalog of antibiotics is a major public health threat. Biofilms are complex, sessile
communities of bacteria embedded in an organic polymer matrix which serve to further
enhance antimicrobial resistance. Consequently, novel compounds and innovative
methods are urgently required to arrest the proliferation of drug-resistant infections in
both nosocomial and community environments. Accordingly, it has been suggested
that antimicrobial peptides could be used as novel natural inhibitors that can be used
in formulations with synergistically acting antibiotics. Nisin is a member of the lantibiotic
family of antimicrobial peptides that exhibit potent antibacterial activity against many
Gram-positive bacteria. Recently we have used bioengineering strategies to enhance
the activity of nisin against several high profile targets, including multi-drug resistant
clinical pathogens such as methicillin-resistant Staphylococcus aureus, vancomycinresistant
enterococci, staphylococci, and streptococci associated with bovine mastitis.
We have also identified nisin derivatives with an enhanced ability to impair biofilm
formation and to reduce the density of established biofilms of methicillin resistant
S. pseudintermedius. The present study was aimed at evaluating the potential of
nisin and nisin derivatives to increase the efficacy of conventional antibiotics and
to assess the possibility of killing and/or eradicating biofilm-associated cells of a
variety of staphylococcal targets. Growth curve-based comparisons established that
combinations of derivatives nisin V C penicillin or nisin I4V C chloramphenicol had
an enhanced inhibitory effect against S. aureus SA113 and S. pseudintermedius
DSM21284, respectively, compared to the equivalent nisin A C antibiotic combinations
or when each antimicrobial was administered alone. Furthermore, the metabolic activity
of established biofilms treated with nisin V C chloramphenicol and nisin I4V C
chloramphenicol combinations revealed a significant decrease in S. aureus SA113 and
S. pseudintermedius DSM21284 biofilm viability, respectively, compared to the nisin A C
antibiotic combinations as determined by the rapid colorimetric XTT assay. The results
indicate that the activities of the nisin derivative and antibiotic combinations represent a
significant improvement over that of the wild-type nisin and antibiotic combination and
merit further investigation with a view to their use as anti-biofilm agents.
