Comparative Transcriptomic and Functional Assessments of Linezolid-Responsive Small RNA Genes in <named-content content-type="genus-species">Staphylococcus aureus</named-content>

ABSTRACT Staphylococcus aureus contains a repertoire of at least 50 and possibly 500 small RNAs (sRNAs). The functions of most sRNAs are not understood, although some are known to respond to environmental changes, including the presence of antibiotics. Here, in an effort to better understand the rol...

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Autores principales:	Wei Gao, Romain Guérillot, Ya Hsun Lin, Jai Tree, Marie Beaume, Patrice François, Ian R. Monk, Torsten Seemann, Jacques Schrenzel, Benjamin P. Howden, Timothy P. Stinear
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	RNA sequencing Staphylococcus aureus mutagenesis postantibiotic effects sRNA transcriptome Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9f94d3d36bc34a64a0306ea8844d02e0
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spelling	oai:doaj.org-article:9f94d3d36bc34a64a0306ea8844d02e02021-12-02T19:47:38ZComparative Transcriptomic and Functional Assessments of Linezolid-Responsive Small RNA Genes in <named-content content-type="genus-species">Staphylococcus aureus</named-content>10.1128/mSystems.00665-192379-5077https://doaj.org/article/9f94d3d36bc34a64a0306ea8844d02e02020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00665-19https://doaj.org/toc/2379-5077ABSTRACT Staphylococcus aureus contains a repertoire of at least 50 and possibly 500 small RNAs (sRNAs). The functions of most sRNAs are not understood, although some are known to respond to environmental changes, including the presence of antibiotics. Here, in an effort to better understand the roles of sRNAs in the context of antibiotic exposure, we took a clinical methicillin-resistant S. aureus (MRSA) isolate and separately deleted eight sRNAs that were significantly upregulated in response to the last-line antibiotic linezolid as revealed by transcriptome sequencing (RNA-seq) comparisons. We also deleted an additional 10 sRNAs that were either highly expressed or previously found to respond to antibiotic exposure. There were no significant changes for any of the 18 mutants in a variety of phenotypic screens, including MIC screens, growth competition assays in the presence of linezolid, biofilm formation, and resistance to whole-blood killing. These data suggest sRNA functional redundancy, because despite their high expression levels upon antibiotic exposure, individual sRNA genes do not affect readily observable bacterial phenotypes. The sRNA transcriptional changes we measured during antibiotic exposure might also reflect sRNA “indifference,” that is, a general stress response not specifically related to sRNA function. These data underscore the need for sensitive assays and new approaches to try and decipher the functions of sRNA genes in S. aureus. IMPORTANCE Bacterial small RNAs (sRNAs) are RNA molecules that can have important regulatory roles across gene expression networks. There is a growing understanding of the scope and potential breadth of impact of sRNAs on global gene expression patterns in Staphylococcus aureus, a major human pathogen. Here, transcriptome comparisons were used to examine the roles of sRNA genes with a potential role in the response of S. aureus to antibiotic exposure. Although no measurable impact on key bacterial phenotypes was observed after deleting each of 18 sRNAs identified by these comparisons, this research is significant because it underscores the subtle modes of action of these sometimes abundant molecules within the bacterium.Wei GaoRomain GuérillotYa Hsun LinJai TreeMarie BeaumePatrice FrançoisIan R. MonkTorsten SeemannJacques SchrenzelBenjamin P. HowdenTimothy P. StinearAmerican Society for MicrobiologyarticleRNA sequencingStaphylococcus aureusmutagenesispostantibiotic effectssRNAtranscriptomeMicrobiologyQR1-502ENmSystems, Vol 5, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	RNA sequencing Staphylococcus aureus mutagenesis postantibiotic effects sRNA transcriptome Microbiology QR1-502
spellingShingle	RNA sequencing Staphylococcus aureus mutagenesis postantibiotic effects sRNA transcriptome Microbiology QR1-502 Wei Gao Romain Guérillot Ya Hsun Lin Jai Tree Marie Beaume Patrice François Ian R. Monk Torsten Seemann Jacques Schrenzel Benjamin P. Howden Timothy P. Stinear Comparative Transcriptomic and Functional Assessments of Linezolid-Responsive Small RNA Genes in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
description	ABSTRACT Staphylococcus aureus contains a repertoire of at least 50 and possibly 500 small RNAs (sRNAs). The functions of most sRNAs are not understood, although some are known to respond to environmental changes, including the presence of antibiotics. Here, in an effort to better understand the roles of sRNAs in the context of antibiotic exposure, we took a clinical methicillin-resistant S. aureus (MRSA) isolate and separately deleted eight sRNAs that were significantly upregulated in response to the last-line antibiotic linezolid as revealed by transcriptome sequencing (RNA-seq) comparisons. We also deleted an additional 10 sRNAs that were either highly expressed or previously found to respond to antibiotic exposure. There were no significant changes for any of the 18 mutants in a variety of phenotypic screens, including MIC screens, growth competition assays in the presence of linezolid, biofilm formation, and resistance to whole-blood killing. These data suggest sRNA functional redundancy, because despite their high expression levels upon antibiotic exposure, individual sRNA genes do not affect readily observable bacterial phenotypes. The sRNA transcriptional changes we measured during antibiotic exposure might also reflect sRNA “indifference,” that is, a general stress response not specifically related to sRNA function. These data underscore the need for sensitive assays and new approaches to try and decipher the functions of sRNA genes in S. aureus. IMPORTANCE Bacterial small RNAs (sRNAs) are RNA molecules that can have important regulatory roles across gene expression networks. There is a growing understanding of the scope and potential breadth of impact of sRNAs on global gene expression patterns in Staphylococcus aureus, a major human pathogen. Here, transcriptome comparisons were used to examine the roles of sRNA genes with a potential role in the response of S. aureus to antibiotic exposure. Although no measurable impact on key bacterial phenotypes was observed after deleting each of 18 sRNAs identified by these comparisons, this research is significant because it underscores the subtle modes of action of these sometimes abundant molecules within the bacterium.
format	article
author	Wei Gao Romain Guérillot Ya Hsun Lin Jai Tree Marie Beaume Patrice François Ian R. Monk Torsten Seemann Jacques Schrenzel Benjamin P. Howden Timothy P. Stinear
author_facet	Wei Gao Romain Guérillot Ya Hsun Lin Jai Tree Marie Beaume Patrice François Ian R. Monk Torsten Seemann Jacques Schrenzel Benjamin P. Howden Timothy P. Stinear
author_sort	Wei Gao
title	Comparative Transcriptomic and Functional Assessments of Linezolid-Responsive Small RNA Genes in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_short	Comparative Transcriptomic and Functional Assessments of Linezolid-Responsive Small RNA Genes in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_full	Comparative Transcriptomic and Functional Assessments of Linezolid-Responsive Small RNA Genes in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_fullStr	Comparative Transcriptomic and Functional Assessments of Linezolid-Responsive Small RNA Genes in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_full_unstemmed	Comparative Transcriptomic and Functional Assessments of Linezolid-Responsive Small RNA Genes in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_sort	comparative transcriptomic and functional assessments of linezolid-responsive small rna genes in <named-content content-type="genus-species">staphylococcus aureus</named-content>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/9f94d3d36bc34a64a0306ea8844d02e0
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Comparative Transcriptomic and Functional Assessments of Linezolid-Responsive Small RNA Genes in <named-content content-type="genus-species">Staphylococcus aureus</named-content>

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