The <named-content content-type="genus-species">Staphylococcus aureus</named-content> Transcriptome during Cystic Fibrosis Lung Infection

ABSTRACT Laboratory models have been invaluable for the field of microbiology for over 100 years and have provided key insights into core aspects of bacterial physiology such as regulation and metabolism. However, it is important to identify the extent to which these models recapitulate bacterial ph...

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Autores principales: Carolyn B. Ibberson, Marvin Whiteley
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Lenguaje:EN
Publicado: American Society for Microbiology 2019
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spelling oai:doaj.org-article:e1982324aba342a087a3752d694ff0c32021-11-15T15:54:47ZThe <named-content content-type="genus-species">Staphylococcus aureus</named-content> Transcriptome during Cystic Fibrosis Lung Infection10.1128/mBio.02774-192150-7511https://doaj.org/article/e1982324aba342a087a3752d694ff0c32019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02774-19https://doaj.org/toc/2150-7511ABSTRACT Laboratory models have been invaluable for the field of microbiology for over 100 years and have provided key insights into core aspects of bacterial physiology such as regulation and metabolism. However, it is important to identify the extent to which these models recapitulate bacterial physiology within a human infection environment. Here, we performed transcriptomics (RNA-seq), focusing on the physiology of the prominent pathogen Staphylococcus aureus in situ in human cystic fibrosis (CF) infection. Through principal-component and hierarchal clustering analyses, we found remarkable conservation in S. aureus gene expression in the CF lung despite differences in the patient clinic, clinical status, age, and therapeutic regimen. We used a machine learning approach to identify an S. aureus transcriptomic signature of 32 genes that can reliably distinguish between S. aureus transcriptomes in the CF lung and in vitro. The majority of these genes were involved in virulence and metabolism and were used to improve a common CF infection model. Collectively, these results advance our knowledge of S. aureus physiology during human CF lung infection and demonstrate how in vitro models can be improved to better capture bacterial physiology in infection. IMPORTANCE Although bacteria have been studied in infection for over 100 years, the majority of these studies have utilized laboratory and animal models that often have unknown relevance to the human infections they are meant to represent. A primary challenge has been to assess bacterial physiology in the human host. To address this challenge, we performed transcriptomics of S. aureus during human cystic fibrosis (CF) lung infection. Using a machine learning framework, we defined a “human CF lung transcriptome signature” that primarily included genes involved in metabolism and virulence. In addition, we were able to apply our findings to improve an in vitro model of CF infection. Understanding bacterial gene expression within human infection is a critical step toward the development of improved laboratory models and new therapeutics.Carolyn B. IbbersonMarvin WhiteleyAmerican Society for MicrobiologyarticleStaphylococcus aureusRNA-seqtranscriptomicsmachine learningvirulencecystic fibrosisMicrobiologyQR1-502ENmBio, Vol 10, Iss 6 (2019)
institution DOAJ
collection DOAJ
language EN
topic Staphylococcus aureus
RNA-seq
transcriptomics
machine learning
virulence
cystic fibrosis
Microbiology
QR1-502
spellingShingle Staphylococcus aureus
RNA-seq
transcriptomics
machine learning
virulence
cystic fibrosis
Microbiology
QR1-502
Carolyn B. Ibberson
Marvin Whiteley
The <named-content content-type="genus-species">Staphylococcus aureus</named-content> Transcriptome during Cystic Fibrosis Lung Infection
description ABSTRACT Laboratory models have been invaluable for the field of microbiology for over 100 years and have provided key insights into core aspects of bacterial physiology such as regulation and metabolism. However, it is important to identify the extent to which these models recapitulate bacterial physiology within a human infection environment. Here, we performed transcriptomics (RNA-seq), focusing on the physiology of the prominent pathogen Staphylococcus aureus in situ in human cystic fibrosis (CF) infection. Through principal-component and hierarchal clustering analyses, we found remarkable conservation in S. aureus gene expression in the CF lung despite differences in the patient clinic, clinical status, age, and therapeutic regimen. We used a machine learning approach to identify an S. aureus transcriptomic signature of 32 genes that can reliably distinguish between S. aureus transcriptomes in the CF lung and in vitro. The majority of these genes were involved in virulence and metabolism and were used to improve a common CF infection model. Collectively, these results advance our knowledge of S. aureus physiology during human CF lung infection and demonstrate how in vitro models can be improved to better capture bacterial physiology in infection. IMPORTANCE Although bacteria have been studied in infection for over 100 years, the majority of these studies have utilized laboratory and animal models that often have unknown relevance to the human infections they are meant to represent. A primary challenge has been to assess bacterial physiology in the human host. To address this challenge, we performed transcriptomics of S. aureus during human cystic fibrosis (CF) lung infection. Using a machine learning framework, we defined a “human CF lung transcriptome signature” that primarily included genes involved in metabolism and virulence. In addition, we were able to apply our findings to improve an in vitro model of CF infection. Understanding bacterial gene expression within human infection is a critical step toward the development of improved laboratory models and new therapeutics.
format article
author Carolyn B. Ibberson
Marvin Whiteley
author_facet Carolyn B. Ibberson
Marvin Whiteley
author_sort Carolyn B. Ibberson
title The <named-content content-type="genus-species">Staphylococcus aureus</named-content> Transcriptome during Cystic Fibrosis Lung Infection
title_short The <named-content content-type="genus-species">Staphylococcus aureus</named-content> Transcriptome during Cystic Fibrosis Lung Infection
title_full The <named-content content-type="genus-species">Staphylococcus aureus</named-content> Transcriptome during Cystic Fibrosis Lung Infection
title_fullStr The <named-content content-type="genus-species">Staphylococcus aureus</named-content> Transcriptome during Cystic Fibrosis Lung Infection
title_full_unstemmed The <named-content content-type="genus-species">Staphylococcus aureus</named-content> Transcriptome during Cystic Fibrosis Lung Infection
title_sort <named-content content-type="genus-species">staphylococcus aureus</named-content> transcriptome during cystic fibrosis lung infection
publisher American Society for Microbiology
publishDate 2019
url https://doaj.org/article/e1982324aba342a087a3752d694ff0c3
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