Transcriptome Remodeling of <italic toggle="yes">Acinetobacter baumannii</italic> during Infection and Treatment

ABSTRACT Acinetobacter baumannii is an increasingly common multidrug-resistant pathogen in health care settings. Although the genetic basis of antibiotic resistance mechanisms has been extensively studied, much less is known about how genetic variation contributes to other aspects of successful infe...

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Autores principales:	Meredith S. Wright, Michael R. Jacobs, Robert A. Bonomo, Mark D. Adams
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a820eccad7e447ee87b581e887307e5e
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spelling	oai:doaj.org-article:a820eccad7e447ee87b581e887307e5e2021-11-15T15:50:59ZTranscriptome Remodeling of <italic toggle="yes">Acinetobacter baumannii</italic> during Infection and Treatment10.1128/mBio.02193-162150-7511https://doaj.org/article/a820eccad7e447ee87b581e887307e5e2017-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02193-16https://doaj.org/toc/2150-7511ABSTRACT Acinetobacter baumannii is an increasingly common multidrug-resistant pathogen in health care settings. Although the genetic basis of antibiotic resistance mechanisms has been extensively studied, much less is known about how genetic variation contributes to other aspects of successful infections. Genetic changes that occur during host infection and treatment have the potential to remodel gene expression patterns related to resistance and pathogenesis. Longitudinal sets of multidrug-resistant A. baumannii isolates from eight patients were analyzed by RNA sequencing (RNA-seq) to identify differentially expressed genes and link them to genetic changes contributing to transcriptional variation at both within-patient and population levels. The number of differentially expressed genes among isolates from the same patient ranged from 26 (patient 588) to 145 (patient 475). Multiple patients had isolates with differential gene expression patterns related to mutations in the pmrAB and adeRS two-component regulatory system genes, as well as significant differences in genes related to antibiotic resistance, iron acquisition, amino acid metabolism, and surface-associated proteins. Population level analysis revealed 39 genetic regions with clade-specific differentially expressed genes, for which 19, 8, and 3 of these could be explained by insertion sequence mobilization, recombination-driven sequence variation, and intergenic mutations, respectively. Multiple types of mutations that arise during infection can significantly remodel the expression of genes that are known to be important in pathogenesis. IMPORTANCE Health care-associated multidrug-resistant Acinetobacter baumannii can cause persistent infections in patients, but bacterial cells must overcome host defenses and antibiotic therapies to do so. Genetic variation arises during host infection, and new mutations are often enriched in genes encoding transcriptional regulators, iron acquisition systems, and surface-associated structures. In this study, genetic variation was shown to result in transcriptome remodeling at the level of individual patients and across phylogenetic groups. Differentially expressed genes include those related to capsule modification, iron acquisition, type I pili, and antibiotic resistance. Population level transcriptional variation reflects genome dynamics over longer evolutionary time periods, and convergent transcriptional changes support the adaptive significance of these regions. Transcriptional changes can be attributed to multiple types of genomic change, but insertion sequence mobilization had a predominant effect. The transcriptional effects of mutations that arise during infection highlight the rapid adaptation of A. baumannii during host exposure.Meredith S. WrightMichael R. JacobsRobert A. BonomoMark D. AdamsAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 8, Iss 2 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Meredith S. Wright Michael R. Jacobs Robert A. Bonomo Mark D. Adams Transcriptome Remodeling of <italic toggle="yes">Acinetobacter baumannii</italic> during Infection and Treatment
description	ABSTRACT Acinetobacter baumannii is an increasingly common multidrug-resistant pathogen in health care settings. Although the genetic basis of antibiotic resistance mechanisms has been extensively studied, much less is known about how genetic variation contributes to other aspects of successful infections. Genetic changes that occur during host infection and treatment have the potential to remodel gene expression patterns related to resistance and pathogenesis. Longitudinal sets of multidrug-resistant A. baumannii isolates from eight patients were analyzed by RNA sequencing (RNA-seq) to identify differentially expressed genes and link them to genetic changes contributing to transcriptional variation at both within-patient and population levels. The number of differentially expressed genes among isolates from the same patient ranged from 26 (patient 588) to 145 (patient 475). Multiple patients had isolates with differential gene expression patterns related to mutations in the pmrAB and adeRS two-component regulatory system genes, as well as significant differences in genes related to antibiotic resistance, iron acquisition, amino acid metabolism, and surface-associated proteins. Population level analysis revealed 39 genetic regions with clade-specific differentially expressed genes, for which 19, 8, and 3 of these could be explained by insertion sequence mobilization, recombination-driven sequence variation, and intergenic mutations, respectively. Multiple types of mutations that arise during infection can significantly remodel the expression of genes that are known to be important in pathogenesis. IMPORTANCE Health care-associated multidrug-resistant Acinetobacter baumannii can cause persistent infections in patients, but bacterial cells must overcome host defenses and antibiotic therapies to do so. Genetic variation arises during host infection, and new mutations are often enriched in genes encoding transcriptional regulators, iron acquisition systems, and surface-associated structures. In this study, genetic variation was shown to result in transcriptome remodeling at the level of individual patients and across phylogenetic groups. Differentially expressed genes include those related to capsule modification, iron acquisition, type I pili, and antibiotic resistance. Population level transcriptional variation reflects genome dynamics over longer evolutionary time periods, and convergent transcriptional changes support the adaptive significance of these regions. Transcriptional changes can be attributed to multiple types of genomic change, but insertion sequence mobilization had a predominant effect. The transcriptional effects of mutations that arise during infection highlight the rapid adaptation of A. baumannii during host exposure.
format	article
author	Meredith S. Wright Michael R. Jacobs Robert A. Bonomo Mark D. Adams
author_facet	Meredith S. Wright Michael R. Jacobs Robert A. Bonomo Mark D. Adams
author_sort	Meredith S. Wright
title	Transcriptome Remodeling of <italic toggle="yes">Acinetobacter baumannii</italic> during Infection and Treatment
title_short	Transcriptome Remodeling of <italic toggle="yes">Acinetobacter baumannii</italic> during Infection and Treatment
title_full	Transcriptome Remodeling of <italic toggle="yes">Acinetobacter baumannii</italic> during Infection and Treatment
title_fullStr	Transcriptome Remodeling of <italic toggle="yes">Acinetobacter baumannii</italic> during Infection and Treatment
title_full_unstemmed	Transcriptome Remodeling of <italic toggle="yes">Acinetobacter baumannii</italic> during Infection and Treatment
title_sort	transcriptome remodeling of <italic toggle="yes">acinetobacter baumannii</italic> during infection and treatment
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/a820eccad7e447ee87b581e887307e5e
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Transcriptome Remodeling of <italic toggle="yes">Acinetobacter baumannii</italic> during Infection and Treatment

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