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VRE ST1421 in Tasmania

ABSTRACT: Draft genome sequence of a new sequence type, ST1421, of Vancomycin-Resistant Enterococcus faecium (VREfm)

PROVIDER: PRJEB25735 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	OOIM02.dat.gz	Other
	OOIM02.fasta.gz	Fasta.gz
	OOIM02.master.dat	Other

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Project description:The rise of antibiotic resistance and decline of antibiotic discovery urgently calls for novel mechanistic understanding of pharmacological and evolutionary interactions between antibiotics and multidrug resistant bacteria to revitalize existing antibiotics. The evolutionary cross-resistance to antibiotics has received intensive attention previously. Nevertheless, whether and how bacteria develop negative responses, under the selective pressure of antibiotics by inverting the evolutionary trajectory remains unclear. Here we found an instance of collateral sensitivity, in which clinical vancomycin-resistant Enterococcus faecium (VREfm) pathogens exhibit dramatic and specific susceptibility to pleuromutilin antibiotics, decreased minimal inhibitory concentrations (MICs) from 128 µg/mL to 0.03 µg/mL. The unique trade-off between vancomycin and pleuromutilins is mediated by the epistasis between the van gene cluster and msrC encoding an ABC-F protein protecting bacterial ribosomes. We validated the efficacy of pleuromutilins in vivo through reducing colonization and promoting microbiota restoration. Our findings provide an alternative approach to inverting the selective advantage and reversing the route of vancomycin resistance evolution, and to treat VREfm associated infections.

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