Abstract
BackgroundThe alarming spread of antimicrobial resistance requires the development of novel anti-infective drugs. Despite the recent research focus on the human microbiome and its likely value to understand and exploit inter-bacterial inhibitory phenomena as a source for antimicrobial strategies, the human microbiota has barely been investigated for the purpose of drug development.ResultsWe performed a large screen analyzing over 3000 human skin isolates to evaluate bacterial competition within the human skin microbiota as a basis for the development of anti-infective therapeutics. We discovered a Staphylococcus hominis strain with strong and broad activity against Gram-positive pathogens that was mediated by the bacteriocin micrococcin P1 (MP1). In “probiotic” approaches, this strain led to reduced Staphylococcus aureus infection and accelerated closure of S. aureus-infected wounds. Furthermore, we used a nanoparticle strategy to overcome the physico-chemical limitations often encountered with natural substances such as MP1 and demonstrate a significant reduction of S. aureus infection by MP1-loaded nanoparticles.ConclusionsOur study gives examples of how analysis of bacterial interactions in the human microbiota can be explored for the development of novel, effective anti-infective strategies.AEGEyk29vyY6bzJ1przWhXVideo
Highlights
The alarming spread of antimicrobial resistance requires the development of novel anti-infective drugs
Analysis of competition among skin bacteria and selection of highly active S. hominis isolate To serve as a basis for the development of an efficient anti-infective, we performed a large screen of the human skin microbiota that was aimed to discover a strongly and broadly competitive commensal skin isolate
S34-1, showed especially broad activity, including against methicillinresistant S. aureus (MRSA) and other Gram-positive bacteria. Further testing of this strain and its culture filtrate revealed that it secretes an antimicrobial activity that inhibits the growth of a series of community, hospital, and livestock-associated MRSA strains, as well as other multidrug-resistant Gram-positive pathogens, including pathogenic and penicillin-resistant streptococci, vancomycin-resistant enterococci (VRE), and methicillinresistant coagulase-negative staphylococci (CoNS) (Table 2, Fig. 2)
Summary
The alarming spread of antimicrobial resistance requires the development of novel anti-infective drugs. Despite the recent research focus on the human microbiome and its likely value to understand and exploit inter-bacterial inhibitory phenomena as a source for antimicrobial strategies, the human microbiota has barely been investigated for the purpose of drug development. The situation of increasing antimicrobial resistance in many bacterial pathogens calls for novel. The skin represents one of several epithelia on the human body where microbial communities exist and live in constant interaction with the host and each other. Commensal skin bacteria are believed to be fundamental for the maintenance of the skin barrier and have been implicated in the protection from infection by pathogenic bacteria and other microorganisms [3]. It is believed that skin commensals exert their protective function in many ways. In addition to educating and supporting the host immune system [5,6,7], they may produce substances to directly impair the growth or virulence of competitors [8, 9]
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