Journal
MICROBIOME
Volume 8, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s40168-020-00866-1
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Funding
- National Natural Science Foundation of China [81873957, 81671975, 81861138043]
- Foundation for Innovative Research Groups of the National Natural Science Foundation of China [81421001]
- Science and Technology Commission of Shanghai Municipality [19JC1413005]
- Shanghai Health System Talents Training Program [2017BR001]
- Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), U.S. National Institutes of Health (NIH) [ZIA AI001080]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZIAAI000904, ZIAAI001080] Funding Source: NIH RePORTER
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Background: 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. Results: 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. Conclusions: 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.
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