CRISPR-Cas and Restriction-Modification Act Additively against Conjugative Antibiotic Resistance Plasmid Transfer in <named-content content-type="genus-species">Enterococcus faecalis</named-content>

ABSTRACT Enterococcus faecalis is an opportunistic pathogen and a leading cause of nosocomial infections. Conjugative pheromone-responsive plasmids are narrow-host-range mobile genetic elements (MGEs) that are rapid disseminators of antibiotic resistance in the faecalis species. Clustered regularly...

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Autores principales:	Valerie J. Price, Wenwen Huo, Ardalan Sharifi, Kelli L. Palmer
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Enterococcus antibiotic resistance CRISPR plasmids horizontal gene transfer Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/98433abd77ad49c18c513af0bb917f09
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spelling	oai:doaj.org-article:98433abd77ad49c18c513af0bb917f092021-11-15T15:21:18ZCRISPR-Cas and Restriction-Modification Act Additively against Conjugative Antibiotic Resistance Plasmid Transfer in <named-content content-type="genus-species">Enterococcus faecalis</named-content>10.1128/mSphere.00064-162379-5042https://doaj.org/article/98433abd77ad49c18c513af0bb917f092016-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00064-16https://doaj.org/toc/2379-5042ABSTRACT Enterococcus faecalis is an opportunistic pathogen and a leading cause of nosocomial infections. Conjugative pheromone-responsive plasmids are narrow-host-range mobile genetic elements (MGEs) that are rapid disseminators of antibiotic resistance in the faecalis species. Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas and restriction-modification confer acquired and innate immunity, respectively, against MGE acquisition in bacteria. Most multidrug-resistant E. faecalis isolates lack CRISPR-Cas and possess an orphan locus lacking cas genes, CRISPR2, that is of unknown function. Little is known about restriction-modification defense in E. faecalis. Here, we explore the hypothesis that multidrug-resistant E. faecalis strains are immunocompromised. We assessed MGE acquisition by E. faecalis T11, a strain closely related to the multidrug-resistant hospital isolate V583 but which lacks the ~620 kb of horizontally acquired genome content that characterizes V583. T11 possesses the E. faecalis CRISPR3-cas locus and a predicted restriction-modification system, neither of which occurs in V583. We demonstrate that CRISPR-Cas and restriction-modification together confer a 4-log reduction in acquisition of the pheromone-responsive plasmid pAM714 in biofilm matings. Additionally, we show that the orphan CRISPR2 locus is functional for genome defense against another pheromone-responsive plasmid, pCF10, only in the presence of cas9 derived from the E. faecalis CRISPR1-cas locus, which most multidrug-resistant E. faecalis isolates lack. Overall, our work demonstrated that the loss of only two loci led to a dramatic reduction in genome defense against a clinically relevant MGE, highlighting the critical importance of the E. faecalis accessory genome in modulating horizontal gene transfer. Our results rationalize the development of antimicrobial strategies that capitalize upon the immunocompromised status of multidrug-resistant E. faecalis. IMPORTANCE Enterococcus faecalis is a bacterium that normally inhabits the gastrointestinal tracts of humans and other animals. Although these bacteria are members of our native gut flora, they can cause life-threatening infections in hospitalized patients. Antibiotic resistance genes appear to be readily shared among high-risk E. faecalis strains, and multidrug resistance in these bacteria limits treatment options for infections. Here, we find that CRISPR-Cas and restriction-modification systems, which function as adaptive and innate immune systems in bacteria, significantly impact the spread of antibiotic resistance genes in E. faecalis populations. The loss of these systems in high-risk E. faecalis suggests that they are immunocompromised, a tradeoff that allows them to readily acquire new genes and adapt to new antibiotics.Valerie J. PriceWenwen HuoArdalan SharifiKelli L. PalmerAmerican Society for MicrobiologyarticleEnterococcusantibiotic resistanceCRISPRplasmidshorizontal gene transferMicrobiologyQR1-502ENmSphere, Vol 1, Iss 3 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Enterococcus antibiotic resistance CRISPR plasmids horizontal gene transfer Microbiology QR1-502
spellingShingle	Enterococcus antibiotic resistance CRISPR plasmids horizontal gene transfer Microbiology QR1-502 Valerie J. Price Wenwen Huo Ardalan Sharifi Kelli L. Palmer CRISPR-Cas and Restriction-Modification Act Additively against Conjugative Antibiotic Resistance Plasmid Transfer in <named-content content-type="genus-species">Enterococcus faecalis</named-content>
description	ABSTRACT Enterococcus faecalis is an opportunistic pathogen and a leading cause of nosocomial infections. Conjugative pheromone-responsive plasmids are narrow-host-range mobile genetic elements (MGEs) that are rapid disseminators of antibiotic resistance in the faecalis species. Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas and restriction-modification confer acquired and innate immunity, respectively, against MGE acquisition in bacteria. Most multidrug-resistant E. faecalis isolates lack CRISPR-Cas and possess an orphan locus lacking cas genes, CRISPR2, that is of unknown function. Little is known about restriction-modification defense in E. faecalis. Here, we explore the hypothesis that multidrug-resistant E. faecalis strains are immunocompromised. We assessed MGE acquisition by E. faecalis T11, a strain closely related to the multidrug-resistant hospital isolate V583 but which lacks the ~620 kb of horizontally acquired genome content that characterizes V583. T11 possesses the E. faecalis CRISPR3-cas locus and a predicted restriction-modification system, neither of which occurs in V583. We demonstrate that CRISPR-Cas and restriction-modification together confer a 4-log reduction in acquisition of the pheromone-responsive plasmid pAM714 in biofilm matings. Additionally, we show that the orphan CRISPR2 locus is functional for genome defense against another pheromone-responsive plasmid, pCF10, only in the presence of cas9 derived from the E. faecalis CRISPR1-cas locus, which most multidrug-resistant E. faecalis isolates lack. Overall, our work demonstrated that the loss of only two loci led to a dramatic reduction in genome defense against a clinically relevant MGE, highlighting the critical importance of the E. faecalis accessory genome in modulating horizontal gene transfer. Our results rationalize the development of antimicrobial strategies that capitalize upon the immunocompromised status of multidrug-resistant E. faecalis. IMPORTANCE Enterococcus faecalis is a bacterium that normally inhabits the gastrointestinal tracts of humans and other animals. Although these bacteria are members of our native gut flora, they can cause life-threatening infections in hospitalized patients. Antibiotic resistance genes appear to be readily shared among high-risk E. faecalis strains, and multidrug resistance in these bacteria limits treatment options for infections. Here, we find that CRISPR-Cas and restriction-modification systems, which function as adaptive and innate immune systems in bacteria, significantly impact the spread of antibiotic resistance genes in E. faecalis populations. The loss of these systems in high-risk E. faecalis suggests that they are immunocompromised, a tradeoff that allows them to readily acquire new genes and adapt to new antibiotics.
format	article
author	Valerie J. Price Wenwen Huo Ardalan Sharifi Kelli L. Palmer
author_facet	Valerie J. Price Wenwen Huo Ardalan Sharifi Kelli L. Palmer
author_sort	Valerie J. Price
title	CRISPR-Cas and Restriction-Modification Act Additively against Conjugative Antibiotic Resistance Plasmid Transfer in <named-content content-type="genus-species">Enterococcus faecalis</named-content>
title_short	CRISPR-Cas and Restriction-Modification Act Additively against Conjugative Antibiotic Resistance Plasmid Transfer in <named-content content-type="genus-species">Enterococcus faecalis</named-content>
title_full	CRISPR-Cas and Restriction-Modification Act Additively against Conjugative Antibiotic Resistance Plasmid Transfer in <named-content content-type="genus-species">Enterococcus faecalis</named-content>
title_fullStr	CRISPR-Cas and Restriction-Modification Act Additively against Conjugative Antibiotic Resistance Plasmid Transfer in <named-content content-type="genus-species">Enterococcus faecalis</named-content>
title_full_unstemmed	CRISPR-Cas and Restriction-Modification Act Additively against Conjugative Antibiotic Resistance Plasmid Transfer in <named-content content-type="genus-species">Enterococcus faecalis</named-content>
title_sort	crispr-cas and restriction-modification act additively against conjugative antibiotic resistance plasmid transfer in <named-content content-type="genus-species">enterococcus faecalis</named-content>
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/98433abd77ad49c18c513af0bb917f09
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CRISPR-Cas and Restriction-Modification Act Additively against Conjugative Antibiotic Resistance Plasmid Transfer in <named-content content-type="genus-species">Enterococcus faecalis</named-content>

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