Skin microbiota analysis-inspired development of novel anti-infectives

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 mi...

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Bibliographic Details
Published in:Microbiome 2020-06, Vol.8 (1), p.85-19, Article 85
Main Authors: Liu, Yao, Liu, Yuanzhen, Du, Zixiu, Zhang, Lidan, Chen, Juan, Shen, Zhen, Liu, Qian, Qin, Juanxiu, Lv, Huiying, Wang, Hua, He, Lei, Liu, Junlan, Huang, Qian, Sun, Yuhui, Otto, Michael, Li, Min
Format: Article
Language:English
Subjects:
Animals
Anti-Infective Agents - pharmacology
Antibiosis
Antimicrobial resistance
Bacteria
Bacteriocins
Competition
Drug development
Female
Humans
Mice
Mice, Inbred BALB C
Mice, Inbred ICR
Microbiomes
Microbiota
Nanoparticles
Penicillin
Probiotics
Skin
Skin - microbiology
Staphylococcal Infections - microbiology
Staphylococcus aureus
Staphylococcus hominis - physiology
Staphylococcus infections
Wound Healing
Wound Infection - microbiology
Young adults
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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. We 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. Our 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. Video Abstract.
ISSN:2049-2618
2049-2618
DOI:10.1186/s40168-020-00866-1