The Evolution of SlyA/RovA Transcription Factors from Repressors to Countersilencers in <italic toggle="yes">Enterobacteriaceae</italic>

ABSTRACT Gene duplication and subsequent evolutionary divergence have allowed conserved proteins to develop unique roles. The MarR family of transcription factors (TFs) has undergone extensive duplication and diversification in bacteria, where they act as environmentally responsive repressors of gen...

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Autores principales:	W. Ryan Will, Peter Brzovic, Isolde Le Trong, Ronald E. Stenkamp, Matthew B. Lawrenz, Joyce E. Karlinsey, William W. Navarre, Kara Main-Hester, Virginia L. Miller, Stephen J. Libby, Ferric C. Fang
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	SlyA countersilencing evolution gene regulation transcription factors Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6e89773f3ee944aa996a1cf09ab4bf04
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spelling	oai:doaj.org-article:6e89773f3ee944aa996a1cf09ab4bf042021-11-15T15:55:25ZThe Evolution of SlyA/RovA Transcription Factors from Repressors to Countersilencers in <italic toggle="yes">Enterobacteriaceae</italic>10.1128/mBio.00009-192150-7511https://doaj.org/article/6e89773f3ee944aa996a1cf09ab4bf042019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00009-19https://doaj.org/toc/2150-7511ABSTRACT Gene duplication and subsequent evolutionary divergence have allowed conserved proteins to develop unique roles. The MarR family of transcription factors (TFs) has undergone extensive duplication and diversification in bacteria, where they act as environmentally responsive repressors of genes encoding efflux pumps that confer resistance to xenobiotics, including many antimicrobial agents. We have performed structural, functional, and genetic analyses of representative members of the SlyA/RovA lineage of MarR TFs, which retain some ancestral functions, including repression of their own expression and that of divergently transcribed multidrug efflux pumps, as well as allosteric inhibition by aromatic carboxylate compounds. However, SlyA and RovA have acquired the ability to countersilence horizontally acquired genes, which has greatly facilitated the evolution of Enterobacteriaceae by horizontal gene transfer. SlyA/RovA TFs in different species have independently evolved novel regulatory circuits to provide the enhanced levels of expression required for their new role. Moreover, in contrast to MarR, SlyA is not responsive to copper. These observations demonstrate the ability of TFs to acquire new functions as a result of evolutionary divergence of both cis-regulatory sequences and in trans interactions with modulatory ligands. IMPORTANCE Bacteria primarily evolve via horizontal gene transfer, acquiring new traits such as virulence and antibiotic resistance in single transfer events. However, newly acquired genes must be integrated into existing regulatory networks to allow appropriate expression in new hosts. This is accommodated in part by the opposing mechanisms of xenogeneic silencing and countersilencing. An understanding of these mechanisms is necessary to understand the relationship between gene regulation and bacterial evolution. Here we examine the functional evolution of an important lineage of countersilencers belonging to the ancient MarR family of classical transcriptional repressors. We show that although members of the SlyA lineage retain some ancestral features associated with the MarR family, their cis-regulatory sequences have evolved significantly to support their new function. Understanding the mechanistic requirements for countersilencing is critical to understanding the pathoadaptation of emerging pathogens and also has practical applications in synthetic biology.W. Ryan WillPeter BrzovicIsolde Le TrongRonald E. StenkampMatthew B. LawrenzJoyce E. KarlinseyWilliam W. NavarreKara Main-HesterVirginia L. MillerStephen J. LibbyFerric C. FangAmerican Society for MicrobiologyarticleSlyAcountersilencingevolutiongene regulationtranscription factorsMicrobiologyQR1-502ENmBio, Vol 10, Iss 2 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	SlyA countersilencing evolution gene regulation transcription factors Microbiology QR1-502
spellingShingle	SlyA countersilencing evolution gene regulation transcription factors Microbiology QR1-502 W. Ryan Will Peter Brzovic Isolde Le Trong Ronald E. Stenkamp Matthew B. Lawrenz Joyce E. Karlinsey William W. Navarre Kara Main-Hester Virginia L. Miller Stephen J. Libby Ferric C. Fang The Evolution of SlyA/RovA Transcription Factors from Repressors to Countersilencers in <italic toggle="yes">Enterobacteriaceae</italic>
description	ABSTRACT Gene duplication and subsequent evolutionary divergence have allowed conserved proteins to develop unique roles. The MarR family of transcription factors (TFs) has undergone extensive duplication and diversification in bacteria, where they act as environmentally responsive repressors of genes encoding efflux pumps that confer resistance to xenobiotics, including many antimicrobial agents. We have performed structural, functional, and genetic analyses of representative members of the SlyA/RovA lineage of MarR TFs, which retain some ancestral functions, including repression of their own expression and that of divergently transcribed multidrug efflux pumps, as well as allosteric inhibition by aromatic carboxylate compounds. However, SlyA and RovA have acquired the ability to countersilence horizontally acquired genes, which has greatly facilitated the evolution of Enterobacteriaceae by horizontal gene transfer. SlyA/RovA TFs in different species have independently evolved novel regulatory circuits to provide the enhanced levels of expression required for their new role. Moreover, in contrast to MarR, SlyA is not responsive to copper. These observations demonstrate the ability of TFs to acquire new functions as a result of evolutionary divergence of both cis-regulatory sequences and in trans interactions with modulatory ligands. IMPORTANCE Bacteria primarily evolve via horizontal gene transfer, acquiring new traits such as virulence and antibiotic resistance in single transfer events. However, newly acquired genes must be integrated into existing regulatory networks to allow appropriate expression in new hosts. This is accommodated in part by the opposing mechanisms of xenogeneic silencing and countersilencing. An understanding of these mechanisms is necessary to understand the relationship between gene regulation and bacterial evolution. Here we examine the functional evolution of an important lineage of countersilencers belonging to the ancient MarR family of classical transcriptional repressors. We show that although members of the SlyA lineage retain some ancestral features associated with the MarR family, their cis-regulatory sequences have evolved significantly to support their new function. Understanding the mechanistic requirements for countersilencing is critical to understanding the pathoadaptation of emerging pathogens and also has practical applications in synthetic biology.
format	article
author	W. Ryan Will Peter Brzovic Isolde Le Trong Ronald E. Stenkamp Matthew B. Lawrenz Joyce E. Karlinsey William W. Navarre Kara Main-Hester Virginia L. Miller Stephen J. Libby Ferric C. Fang
author_facet	W. Ryan Will Peter Brzovic Isolde Le Trong Ronald E. Stenkamp Matthew B. Lawrenz Joyce E. Karlinsey William W. Navarre Kara Main-Hester Virginia L. Miller Stephen J. Libby Ferric C. Fang
author_sort	W. Ryan Will
title	The Evolution of SlyA/RovA Transcription Factors from Repressors to Countersilencers in <italic toggle="yes">Enterobacteriaceae</italic>
title_short	The Evolution of SlyA/RovA Transcription Factors from Repressors to Countersilencers in <italic toggle="yes">Enterobacteriaceae</italic>
title_full	The Evolution of SlyA/RovA Transcription Factors from Repressors to Countersilencers in <italic toggle="yes">Enterobacteriaceae</italic>
title_fullStr	The Evolution of SlyA/RovA Transcription Factors from Repressors to Countersilencers in <italic toggle="yes">Enterobacteriaceae</italic>
title_full_unstemmed	The Evolution of SlyA/RovA Transcription Factors from Repressors to Countersilencers in <italic toggle="yes">Enterobacteriaceae</italic>
title_sort	evolution of slya/rova transcription factors from repressors to countersilencers in <italic toggle="yes">enterobacteriaceae</italic>
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/6e89773f3ee944aa996a1cf09ab4bf04
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The Evolution of SlyA/RovA Transcription Factors from Repressors to Countersilencers in <italic toggle="yes">Enterobacteriaceae</italic>

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