Mining and statistical modeling of natural and variant class IIa bacteriocins elucidates activity and selectivity profiles across species.

Mining and statistical modeling of natural and variant class IIa bacteriocins elucidates activity and selectivity profiles across species. Appl Environ Microbiol. 2020 Sep 11;: Authors: Tresnak DT, Hackel BJ Abstract Class IIa bacteriocin antimicrobial peptides (AMPs) are a compelling alternative to current antimicrobials because of potential specific activity towards antibiotic-resistant bacteria, including vancomycin-resistant enterococci. Engineering of these molecules would be enhanced by a better understanding of AMP sequence-activity relationships to improve efficacy in vivo and limit effects of off-target activity. Towards this goal, we experimentally evaluated 210 natural and variant class IIa bacteriocins for antimicrobial activity against six strains of enterococci. Inhibitory activity was ridge regressed to AMP sequence to predict performance, achieving an area under the curve of 0.70 and demonstrating the potential of statistical models for identifying and designing AMPs. Active AMPs were individually produced and evaluated against eight enterococci strains and four Listeria strains to elucidate trends in susceptibility. It was determined that the mannose phosphotransferase system sequence is informative of susceptibility to class IIa bacteriocins, yet other factors, such as membrane composition, also contribute strongly to susceptibility. A broadly potent bacteriocin variant (lactocin DT1) from a Lactobacillus ruminis ge...
Source: Applied and Environmental Microbiology - Category: Microbiology Authors: Tags: Appl Environ Microbiol Source Type: research