Genes Contributing to the Unique Biology and Intrinsic Antibiotic Resistance of <named-content content-type="genus-species">Enterococcus faecalis</named-content>

ABSTRACT The enterococci, which are among the leading causes of multidrug-resistant (MDR) hospital infection, are notable for their environmental ruggedness, which extends to intrinsic antibiotic resistance. To identify genes that confer this unique property, we used Tn-seq to comprehensively explor...

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Autores principales:	Michael S. Gilmore, Rauf Salamzade, Elizabeth Selleck, Noelle Bryan, Suelen S. Mello, Abigail L. Manson, Ashlee M. Earl
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Enterococcus faecalis antibiotic resistance evolutionary biology genomes metabolism cell wall Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/529c6caa92864da3b8cc8cb83ce415cd
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spelling	oai:doaj.org-article:529c6caa92864da3b8cc8cb83ce415cd2021-11-15T15:55:43ZGenes Contributing to the Unique Biology and Intrinsic Antibiotic Resistance of <named-content content-type="genus-species">Enterococcus faecalis</named-content>10.1128/mBio.02962-202150-7511https://doaj.org/article/529c6caa92864da3b8cc8cb83ce415cd2020-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02962-20https://doaj.org/toc/2150-7511ABSTRACT The enterococci, which are among the leading causes of multidrug-resistant (MDR) hospital infection, are notable for their environmental ruggedness, which extends to intrinsic antibiotic resistance. To identify genes that confer this unique property, we used Tn-seq to comprehensively explore the genome of MDR Enterococcus faecalis strain MMH594 for genes important for growth in nutrient-containing medium and with low-level antibiotic challenge. As expected, a large core of genes for DNA replication, expression, and central metabolism, shared with other bacteria, are intolerant to transposon disruption. However, genes were identified that are important to E. faecalis that are either absent from or unimportant for Staphylococcus aureus and Streptococcus pneumoniae fitness when similarly tested. Further, 217 genes were identified that when challenged by sub-MIC antibiotic levels exhibited reduced tolerance to transposon disruption, including those previously shown to contribute to intrinsic resistance, and others not previously ascribed this role. E. faecalis is one of the few Gram-positive bacteria experimentally shown to possess a functional Entner-Doudoroff pathway for carbon metabolism, a pathway that contributes to stress tolerance in other microbes. Through functional genomics and network analysis we defined the unusual structure of this pathway in E. faecalis and assessed its importance. These approaches also identified toxin-antitoxin and related systems that are unique and active in E. faecalis. Finally, we identified genes that are absent in the closest nonenterococcal relatives, the vagococci, and that contribute importantly to fitness with and without antibiotic selection, advancing an understanding of the unique biology of enterococci. IMPORTANCE Enterococci are leading causes of antibiotic-resistant infection transmitted in hospitals. The intrinsic hardiness of these organisms allows them to survive disinfection practices and then proliferate in the gastrointestinal tracts of antibiotic-treated patients. The objective of this study was to identify the underlying genetic basis for its unusual hardiness. Using a functional genomic approach, we identified traits and pathways of general importance for enterococcal survival and growth that distinguish them from closely related pathogens as well as ancestrally related species. We further identified unique traits that enable them to survive antibiotic challenge, revealing a large set of genes that contribute to intrinsic antibiotic resistance and a smaller set of uniquely important genes that are rare outside enterococci.Michael S. GilmoreRauf SalamzadeElizabeth SelleckNoelle BryanSuelen S. MelloAbigail L. MansonAshlee M. EarlAmerican Society for MicrobiologyarticleEnterococcus faecalisantibiotic resistanceevolutionary biologygenomesmetabolismcell wallMicrobiologyQR1-502ENmBio, Vol 11, Iss 6 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Enterococcus faecalis antibiotic resistance evolutionary biology genomes metabolism cell wall Microbiology QR1-502
spellingShingle	Enterococcus faecalis antibiotic resistance evolutionary biology genomes metabolism cell wall Microbiology QR1-502 Michael S. Gilmore Rauf Salamzade Elizabeth Selleck Noelle Bryan Suelen S. Mello Abigail L. Manson Ashlee M. Earl Genes Contributing to the Unique Biology and Intrinsic Antibiotic Resistance of <named-content content-type="genus-species">Enterococcus faecalis</named-content>
description	ABSTRACT The enterococci, which are among the leading causes of multidrug-resistant (MDR) hospital infection, are notable for their environmental ruggedness, which extends to intrinsic antibiotic resistance. To identify genes that confer this unique property, we used Tn-seq to comprehensively explore the genome of MDR Enterococcus faecalis strain MMH594 for genes important for growth in nutrient-containing medium and with low-level antibiotic challenge. As expected, a large core of genes for DNA replication, expression, and central metabolism, shared with other bacteria, are intolerant to transposon disruption. However, genes were identified that are important to E. faecalis that are either absent from or unimportant for Staphylococcus aureus and Streptococcus pneumoniae fitness when similarly tested. Further, 217 genes were identified that when challenged by sub-MIC antibiotic levels exhibited reduced tolerance to transposon disruption, including those previously shown to contribute to intrinsic resistance, and others not previously ascribed this role. E. faecalis is one of the few Gram-positive bacteria experimentally shown to possess a functional Entner-Doudoroff pathway for carbon metabolism, a pathway that contributes to stress tolerance in other microbes. Through functional genomics and network analysis we defined the unusual structure of this pathway in E. faecalis and assessed its importance. These approaches also identified toxin-antitoxin and related systems that are unique and active in E. faecalis. Finally, we identified genes that are absent in the closest nonenterococcal relatives, the vagococci, and that contribute importantly to fitness with and without antibiotic selection, advancing an understanding of the unique biology of enterococci. IMPORTANCE Enterococci are leading causes of antibiotic-resistant infection transmitted in hospitals. The intrinsic hardiness of these organisms allows them to survive disinfection practices and then proliferate in the gastrointestinal tracts of antibiotic-treated patients. The objective of this study was to identify the underlying genetic basis for its unusual hardiness. Using a functional genomic approach, we identified traits and pathways of general importance for enterococcal survival and growth that distinguish them from closely related pathogens as well as ancestrally related species. We further identified unique traits that enable them to survive antibiotic challenge, revealing a large set of genes that contribute to intrinsic antibiotic resistance and a smaller set of uniquely important genes that are rare outside enterococci.
format	article
author	Michael S. Gilmore Rauf Salamzade Elizabeth Selleck Noelle Bryan Suelen S. Mello Abigail L. Manson Ashlee M. Earl
author_facet	Michael S. Gilmore Rauf Salamzade Elizabeth Selleck Noelle Bryan Suelen S. Mello Abigail L. Manson Ashlee M. Earl
author_sort	Michael S. Gilmore
title	Genes Contributing to the Unique Biology and Intrinsic Antibiotic Resistance of <named-content content-type="genus-species">Enterococcus faecalis</named-content>
title_short	Genes Contributing to the Unique Biology and Intrinsic Antibiotic Resistance of <named-content content-type="genus-species">Enterococcus faecalis</named-content>
title_full	Genes Contributing to the Unique Biology and Intrinsic Antibiotic Resistance of <named-content content-type="genus-species">Enterococcus faecalis</named-content>
title_fullStr	Genes Contributing to the Unique Biology and Intrinsic Antibiotic Resistance of <named-content content-type="genus-species">Enterococcus faecalis</named-content>
title_full_unstemmed	Genes Contributing to the Unique Biology and Intrinsic Antibiotic Resistance of <named-content content-type="genus-species">Enterococcus faecalis</named-content>
title_sort	genes contributing to the unique biology and intrinsic antibiotic resistance of <named-content content-type="genus-species">enterococcus faecalis</named-content>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/529c6caa92864da3b8cc8cb83ce415cd
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Genes Contributing to the Unique Biology and Intrinsic Antibiotic Resistance of <named-content content-type="genus-species">Enterococcus faecalis</named-content>

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