Vancomycin resistant enterococci (VRE) are important pathogens in hospitalized patients, however, the factors involved in VRE colonization of hospitalized patients are not well characterized. Bacteriocins provide a competitive advantage to enterococci in experimental models of colonization, but little is known about bacteriocin content in samples derived from humans and even less is known about their dynamics in the clinical setting. To identify bacteriocins which may be relevant in the transmission of VRE, we present a systematic analysis of bacteriocin content in the genomes of 2,428 patient derived E. faecium isolates collected over a six-year period from a single hospital system. We used computational methods to broadly search for bacteriocin structural genes and a functional assay to look for phenotypes consistent with bacteriocin expression. We identified homology to 15 different bacteriocins with two having high presence in this clinical cohort. Bacteriocin 43 (bac43) was found in a total of 58% of isolates, increasing from 8% to 91% presence over the six-year collection period. There was little genetic variation in the bac43 structural or immunity genes across isolates. The enterocin A structural gene was found in 98% of isolates but only 0.3% of isolates had an intact enterocin A gene cluster and displayed a bacteriocin producing phenotype. This study presents a wide survey of bacteriocins from hospital isolates and identified bac43 as highly conserved, increasing in prevalence, and phenotypically functional. This makes bac43 an interesting target for future investigation for a potential role in E. faecium transmission.

The authors have declared no competing interest.

AG was supported by the Molecular Mechanisms in Microbial Pathogenesis Training Program (T32 AI007528) and the University of Michigan Integrated Training in Microbial Systems (grant from Burroughs Wellcome Fund: Institutional Program Unifying Population and Laboratory Based Sciences). This work was supported by the National Institutes of Health under Grant No. R01 AI143852 to R.J.W.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study was approved by the University of Michigan Institutional Review Board (ID no. HUM00102282), which determined that informed consent was not required as all data utilized were collected for patient treatment purposes.

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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All scripts and pipelines are available on GitHub (https://github.com/woodslab/bacteriocin_search). The whole genome sequencing project for our reference E. faecium isolates have been deposited at DDBJ/ENA/GenBank: BL00198- 1 (accession JBEFKN000000000), BL02040- 1 (accession JBEFKM000000000), PR46485-1-C1 (JBEFKL000000000). The versions described in this paper are JBEFKN010000000, JBEFKM010000000, and JBEFKL010000000, respectively.

https://github.com/woodslab/bacteriocin_search