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Bioengineered Nisin Derivative M17Q Has Enhanced Activity against Staphylococcus epidermidis.

ABSTRACT: Staphylococcus epidermidis is frequently implicated in medical device-related infections. As a result of this, novel approaches for control of this opportunistic pathogen are required. We examined the ability of the natural peptide nisin A, produced by Lactococcus lactis, to inhibit S. epidermidis. In addition, a bank of 29 rationally selected bioengineered L. lactis strains were examined with the aim of identifying a nisin derivative with enhanced antimicrobial activity. Agar-based deferred antagonism assays revealed that wild type nisin A inhibited all 18 S. epidermidis strains tested. Larger zones of inhibition than those obtained from the nisin A producing L. lactis strain were observed for each derivative producer against at least one S. epidermidis strain tested. Six derivative producing strains, (VGA, VGT, SGK, M21A, M17Q, AAA), gave larger zones against all 18 strains compared to the wildtype producing strain. The enhanced bioactivity of M17Q was confirmed using well diffusion, minimum inhibitory concentration (MIC) and a broth-based survival assays. Biofilm assays were performed with plastic microtiter plates and medical device substrates (stainless-steel coupons and three catheter materials). The presence of nisin A significantly reduce the amount of biofilm formed on all surfaces. M17Q was significantly better at reducing biofilm production than nisin A on plastic and stainless-steel. Finally, M17Q was significantly better than nisin A at reducing bacterial numbers in a simulated wound fluid. The findings of this study suggest that nisin and bioengineered derivatives warrant further investigation as potential strategies for the control of S. epidermidis.

SUBMITTER: Twomey E

PROVIDER: S-EPMC7345907 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Bioengineered Nisin Derivative M17Q Has Enhanced Activity against Staphylococcus epidermidis.

Twomey Ellen E Hill Colin C Field Des D Begley Maire M

Antibiotics (Basel, Switzerland) 20200606 6

Staphylococcus epidermidis is frequently implicated in medical device-related infections. As a result of this, novel approaches for control of this opportunistic pathogen are required. We examined the ability of the natural peptide nisin A, produced by Lactococcus lactis, to inhibit S. epidermidis. In addition, a bank of 29 rationally selected bioengineered L. lactis strains were examined with the aim of identifying a nisin derivative with enhanced antimicrobial activ ...[more]

PMID: 32517174

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Project description:The ability of Staphylococcus epidermidis and S. aureus to form strong biofilm on plastic devices makes them the major pathogens associated with device-related infections (DRIs). Biofilm-embedded bacteria are more resistant to antibiotics, making biofilm infections very difficult to effectively treat. Here, we evaluate the in vitro activities of anti-staphylococcal drug oxacillin and antimicrobial peptide nisin, alone and in combination, against methicillin-resistant S. epidermidis (MRSE) clinical isolates and the methicillin-resistant S. aureus ATCC 43,300. The minimum inhibitory concentrations (MIC) and minimum biofilm eradication concentrations (MBEC) of oxacillin and nisin were determined using the microbroth dilution method. The anti-biofilm activities of oxacillin and nisin, alone or in combination, were evaluated. In addition, the effects of antimicrobial agents on the expression of icaA gene were examined by quantitative real-time PCR. MIC values for oxacillin and nisin ranged 4-8 µg/mL and 64-128 µg/mL, respectively. Oxacillin and nisin reduced biofilm biomass in all bacteria in a dose-dependent manner and this inhibitory effect was enhanced with combinatorial treatment. MBEC ranges for oxacillin and nisin were 2048-8192 µg/mL and 2048-4096 µg/mL, respectively. The addition of nisin significantly decreased the oxacillin MBECs from 8- to 32-fold in all bacteria. At the 1× MIC and 1/2× MIC, both oxacillin and nisin decreased significantly the expression of icaA gene in comparison with untreated control. When two antimicrobial agents were combined at 1/2× MIC concentration, the expression of icaA were significantly lower than when were used alone. Nisin/conventional oxacillin combination showed considerable anti-biofilm effects, including inhibition of biofilm formation, eradication of mature biofilm, and down-regulation of biofilm-related genes, proposing its applications for treating or preventing staphylococcal biofilm-associated infections, including device-related infections.

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Bioengineered Nisin Derivative M17Q Has Enhanced Activity against Staphylococcus epidermidis.

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Bioengineered Nisin Derivative M17Q Has Enhanced Activity against <i>Staphylococcus epidermidis</i>.

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