Microbiota-derived lantibiotic restores resistance against vancomycin-resistant Enterococcus.
Sohn G Kim1,2, Simone Becattini1, Thomas U Moody1,3
1Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nature
|August 23, 2019
Summary
Blautia producta BPSCSK, a gut bacterium, produces a lantibiotic that reduces vancomycin-resistant Enterococcus faecium (VRE) colonization. This commensal bacterium and its antibiotic show promise as probiotics against VRE infections.
Area of Science:
- Microbiology
- Gastroenterology
- Infectious Diseases
Background:
- Intestinal commensal bacteria normally prevent colonization by vancomycin-resistant Enterococcus faecium (VRE).
- Antibiotic use can disrupt this barrier, increasing susceptibility to VRE, a common cause of hospital-acquired infections.
- A specific commensal consortium, including Blautia producta BPSCSK, has shown potential in reversing antibiotic-induced VRE susceptibility.
Purpose of the Study:
- To investigate the mechanism by which Blautia producta BPSCSK inhibits VRE colonization.
- To compare the efficacy of BPSCSK and its secreted lantibiotic against VRE in vitro and in vivo.
- To explore the potential of lantibiotic-producing commensals as probiotics for VRE resistance.
Main Methods:
- Investigated BPSCSK's mechanism of VRE inhibition, identifying a secreted lantibiotic.
- Compared the in vitro and in vivo effects of BPSCSK and Lactococcus lactis on VRE growth and colonization.
- Analyzed the association between lantibiotic gene abundance and E. faecium density in patient samples and germ-free mice.
Main Results:
- BPSCSK inhibits VRE by secreting a lantibiotic similar to nisin-A.
- While both BPSCSK and L. lactis inhibit VRE in vitro, only BPSCSK effectively reduces VRE density in vivo.
- The BPSCSK lantibiotic exhibits reduced activity against commensal bacteria compared to nisin-A.
- High lantibiotic gene abundance in patients and mice correlates with reduced VRE density.
Conclusions:
- Lantibiotic-producing commensal bacteria, like BPSCSK, can effectively reduce VRE colonization in the gut.
- The BPSCSK-derived lantibiotic offers a targeted approach with less impact on beneficial gut flora.
- These findings support the development of lantibiotic-producing commensals as probiotics to combat VRE infections.
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