High-Resolution Transcriptomic Analysis of the Adaptive Response of <named-content content-type="genus-species">Staphylococcus aureus</named-content> during Acute and Chronic Phases of Osteomyelitis

ABSTRACT Osteomyelitis is a difficult-to-eradicate bone infection typically caused by Staphylococcus aureus. In this study, we investigated the in vivo transcriptional adaptation of S. aureus during bone infection. To this end, we determined the transcriptome of S. aureus during the acute (day 7) an...

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Autores principales:	Anna K. Szafranska, Andrew P. A. Oxley, Diego Chaves-Moreno, Sarah A. Horst, Steffen Roßlenbroich, Georg Peters, Oliver Goldmann, Manfred Rohde, Bhanu Sinha, Dietmar H. Pieper, Bettina Löffler, Ruy Jauregui, Melissa L. Wos-Oxley, Eva Medina
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Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b54debd443564f7d9e639f97710977c1
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spelling	oai:doaj.org-article:b54debd443564f7d9e639f97710977c12021-11-15T15:47:04ZHigh-Resolution Transcriptomic Analysis of the Adaptive Response of <named-content content-type="genus-species">Staphylococcus aureus</named-content> during Acute and Chronic Phases of Osteomyelitis10.1128/mBio.01775-142150-7511https://doaj.org/article/b54debd443564f7d9e639f97710977c12014-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01775-14https://doaj.org/toc/2150-7511ABSTRACT Osteomyelitis is a difficult-to-eradicate bone infection typically caused by Staphylococcus aureus. In this study, we investigated the in vivo transcriptional adaptation of S. aureus during bone infection. To this end, we determined the transcriptome of S. aureus during the acute (day 7) and chronic (day 28) phases of experimental murine osteomyelitis using RNA sequencing (RNA-Seq). We identified a total of 180 genes significantly more highly expressed by S. aureus during acute or chronic in vivo infection than under in vitro growth conditions. These genes encoded proteins involved in gluconeogenesis, proteolysis of host proteins, iron acquisition, evasion of host immune defenses, and stress responses. At the regulatory level, sarA and -R and saeR and -S as well as the small RNA RsaC were predominantly expressed by S. aureus during in vivo infection. Only nine genes, including the genes encoding the arginine deiminase (ADI) pathway and those involved in the stringent response, were significantly more highly expressed by S. aureus during the chronic than the acute stage of infection. Analysis by quantitative reverse transcription-PCR (qRT-PCR) of a subset of these in vivo-expressed genes in clinical specimens yielded the same results as those observed in the murine system. Collectively, our results show that during acute osteomyelitis, S. aureus induced the transcription of genes that mediate metabolic adaptation, immune evasion, and replication. During the chronic phase, however, S. aureus switched its transcriptional response from a proliferative to a persistence mode, probably driven by the severe deficiency in nutrient supplies. Interfering with the survival strategies of S. aureus during chronic infection could lead to more effective treatments. IMPORTANCE The key to the survival success of pathogens during an infection is their capacity to rapidly adjust to the host environment and to evade the host defenses. Understanding how a pathogen redirects and fine-tunes its gene expression in response to the challenges of infection is central to the development of more efficient anti-infective therapies. Osteomyelitis is a debilitating infection of the bone predominantly caused by S. aureus. In this study, we evaluated the transcriptional response of S. aureus during bone infection. Our results indicate that S. aureus reprograms its genetic repertoire during the acute phase of infection to adapt to nutrient availability and to replicate within the host. During the chronic phase, S. aureus upregulates a survival genetic program activated in response to nutrient starvation. Thus, we have uncovered key survival pathways of S. aureus during acute and chronic osteomyelitis that can be used as therapeutic targets.Anna K. SzafranskaAndrew P. A. OxleyDiego Chaves-MorenoSarah A. HorstSteffen RoßlenbroichGeorg PetersOliver GoldmannManfred RohdeBhanu SinhaDietmar H. PieperBettina LöfflerRuy JaureguiMelissa L. Wos-OxleyEva MedinaAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 6 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Anna K. Szafranska Andrew P. A. Oxley Diego Chaves-Moreno Sarah A. Horst Steffen Roßlenbroich Georg Peters Oliver Goldmann Manfred Rohde Bhanu Sinha Dietmar H. Pieper Bettina Löffler Ruy Jauregui Melissa L. Wos-Oxley Eva Medina High-Resolution Transcriptomic Analysis of the Adaptive Response of <named-content content-type="genus-species">Staphylococcus aureus</named-content> during Acute and Chronic Phases of Osteomyelitis
description	ABSTRACT Osteomyelitis is a difficult-to-eradicate bone infection typically caused by Staphylococcus aureus. In this study, we investigated the in vivo transcriptional adaptation of S. aureus during bone infection. To this end, we determined the transcriptome of S. aureus during the acute (day 7) and chronic (day 28) phases of experimental murine osteomyelitis using RNA sequencing (RNA-Seq). We identified a total of 180 genes significantly more highly expressed by S. aureus during acute or chronic in vivo infection than under in vitro growth conditions. These genes encoded proteins involved in gluconeogenesis, proteolysis of host proteins, iron acquisition, evasion of host immune defenses, and stress responses. At the regulatory level, sarA and -R and saeR and -S as well as the small RNA RsaC were predominantly expressed by S. aureus during in vivo infection. Only nine genes, including the genes encoding the arginine deiminase (ADI) pathway and those involved in the stringent response, were significantly more highly expressed by S. aureus during the chronic than the acute stage of infection. Analysis by quantitative reverse transcription-PCR (qRT-PCR) of a subset of these in vivo-expressed genes in clinical specimens yielded the same results as those observed in the murine system. Collectively, our results show that during acute osteomyelitis, S. aureus induced the transcription of genes that mediate metabolic adaptation, immune evasion, and replication. During the chronic phase, however, S. aureus switched its transcriptional response from a proliferative to a persistence mode, probably driven by the severe deficiency in nutrient supplies. Interfering with the survival strategies of S. aureus during chronic infection could lead to more effective treatments. IMPORTANCE The key to the survival success of pathogens during an infection is their capacity to rapidly adjust to the host environment and to evade the host defenses. Understanding how a pathogen redirects and fine-tunes its gene expression in response to the challenges of infection is central to the development of more efficient anti-infective therapies. Osteomyelitis is a debilitating infection of the bone predominantly caused by S. aureus. In this study, we evaluated the transcriptional response of S. aureus during bone infection. Our results indicate that S. aureus reprograms its genetic repertoire during the acute phase of infection to adapt to nutrient availability and to replicate within the host. During the chronic phase, S. aureus upregulates a survival genetic program activated in response to nutrient starvation. Thus, we have uncovered key survival pathways of S. aureus during acute and chronic osteomyelitis that can be used as therapeutic targets.
format	article
author	Anna K. Szafranska Andrew P. A. Oxley Diego Chaves-Moreno Sarah A. Horst Steffen Roßlenbroich Georg Peters Oliver Goldmann Manfred Rohde Bhanu Sinha Dietmar H. Pieper Bettina Löffler Ruy Jauregui Melissa L. Wos-Oxley Eva Medina
author_facet	Anna K. Szafranska Andrew P. A. Oxley Diego Chaves-Moreno Sarah A. Horst Steffen Roßlenbroich Georg Peters Oliver Goldmann Manfred Rohde Bhanu Sinha Dietmar H. Pieper Bettina Löffler Ruy Jauregui Melissa L. Wos-Oxley Eva Medina
author_sort	Anna K. Szafranska
title	High-Resolution Transcriptomic Analysis of the Adaptive Response of <named-content content-type="genus-species">Staphylococcus aureus</named-content> during Acute and Chronic Phases of Osteomyelitis
title_short	High-Resolution Transcriptomic Analysis of the Adaptive Response of <named-content content-type="genus-species">Staphylococcus aureus</named-content> during Acute and Chronic Phases of Osteomyelitis
title_full	High-Resolution Transcriptomic Analysis of the Adaptive Response of <named-content content-type="genus-species">Staphylococcus aureus</named-content> during Acute and Chronic Phases of Osteomyelitis
title_fullStr	High-Resolution Transcriptomic Analysis of the Adaptive Response of <named-content content-type="genus-species">Staphylococcus aureus</named-content> during Acute and Chronic Phases of Osteomyelitis
title_full_unstemmed	High-Resolution Transcriptomic Analysis of the Adaptive Response of <named-content content-type="genus-species">Staphylococcus aureus</named-content> during Acute and Chronic Phases of Osteomyelitis
title_sort	high-resolution transcriptomic analysis of the adaptive response of <named-content content-type="genus-species">staphylococcus aureus</named-content> during acute and chronic phases of osteomyelitis
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/b54debd443564f7d9e639f97710977c1
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High-Resolution Transcriptomic Analysis of the Adaptive Response of <named-content content-type="genus-species">Staphylococcus aureus</named-content> during Acute and Chronic Phases of Osteomyelitis

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