High-resolution transcriptomic analysis of the adaptive response of Staphylococcus aureus during acute and chronic phases of osteomyelitis.

2.50
Hdl Handle:
http://hdl.handle.net/10033/575929
Title:
High-resolution transcriptomic analysis of the adaptive response of Staphylococcus aureus during acute and chronic phases of osteomyelitis.
Authors:
Szafranska, Anna K; Oxley, Andrew P A; Chaves-Moreno, Diego; Horst, Sarah A; Roßlenbroich, Steffen; Peters, Georg; Goldmann, Oliver; Rohde, Manfred ( 0000-0003-0522-3580 ) ; Sinha, Bhanu; Pieper, Dietmar H; Löffler, Bettina; Jauregui, Ruy; Wos-Oxley, Melissa L; Medina, Eva ( 0000-0001-9073-0223 )
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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
High-resolution transcriptomic analysis of the adaptive response of Staphylococcus aureus during acute and chronic phases of osteomyelitis. 2014, 5 (6): MBio
Journal:
mBio
Issue Date:
2014
URI:
http://hdl.handle.net/10033/575929
DOI:
10.1128/mBio.01775-14
PubMed ID:
25538190
Type:
Article
Language:
en
ISSN:
2150-7511
Appears in Collections:
publications of the research group immunology of infection (INI)

Full metadata record

DC FieldValue Language
dc.contributor.authorSzafranska, Anna Ken
dc.contributor.authorOxley, Andrew P Aen
dc.contributor.authorChaves-Moreno, Diegoen
dc.contributor.authorHorst, Sarah Aen
dc.contributor.authorRoßlenbroich, Steffenen
dc.contributor.authorPeters, Georgen
dc.contributor.authorGoldmann, Oliveren
dc.contributor.authorRohde, Manfreden
dc.contributor.authorSinha, Bhanuen
dc.contributor.authorPieper, Dietmar Hen
dc.contributor.authorLöffler, Bettinaen
dc.contributor.authorJauregui, Ruyen
dc.contributor.authorWos-Oxley, Melissa Len
dc.contributor.authorMedina, Evaen
dc.date.accessioned2015-08-25T12:44:17Zen
dc.date.available2015-08-25T12:44:17Zen
dc.date.issued2014en
dc.identifier.citationHigh-resolution transcriptomic analysis of the adaptive response of Staphylococcus aureus during acute and chronic phases of osteomyelitis. 2014, 5 (6): MBioen
dc.identifier.issn2150-7511en
dc.identifier.pmid25538190en
dc.identifier.doi10.1128/mBio.01775-14en
dc.identifier.urihttp://hdl.handle.net/10033/575929en
dc.description.abstractOsteomyelitis 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.en
dc.language.isoenen
dc.subject.meshAdaptation, Physiologicalen
dc.subject.meshAnimalsen
dc.subject.meshDisease Models, Animalen
dc.subject.meshGene Expressionen
dc.subject.meshGene Expression Profilingen
dc.subject.meshMiceen
dc.subject.meshOsteomyelitisen
dc.subject.meshReal-Time Polymerase Chain Reactionen
dc.subject.meshStaphylococcus aureusen
dc.subject.meshStress, Physiologicalen
dc.titleHigh-resolution transcriptomic analysis of the adaptive response of Staphylococcus aureus during acute and chronic phases of osteomyelitis.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalmBioen

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