Diverse modulation of spa transcription by cell wall active antibiotics in Staphylococcus aureus

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Diverse modulation of spa transcription by cell wall active antibiotics in Staphylococcus aureus. / Nielsen, Lene Nørby; Roggenbuck, Michael; Haaber, Jakob ; Ifrah, Dan; Ingmer, Hanne.

In: BMC Research Notes, Vol. 5, No. 1, 457, 2012.

Research output: Contribution to journalJournal article – Annual report year: 2012Researchpeer-review

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Nielsen, Lene Nørby ; Roggenbuck, Michael ; Haaber, Jakob ; Ifrah, Dan ; Ingmer, Hanne. / Diverse modulation of spa transcription by cell wall active antibiotics in Staphylococcus aureus. In: BMC Research Notes. 2012 ; Vol. 5, No. 1.

Bibtex

@article{4e4f10321da04ba58468618c3384a28f,
title = "Diverse modulation of spa transcription by cell wall active antibiotics in Staphylococcus aureus",
abstract = "Abstract. Background: The aim of this study was to investigate the effect of various classes of clinically relevant antibiotics at sub-lethal concentrations on virulence gene expression and biofilm formation in Staphylococcus aureus. Findings. LacZ promoter fusions of genes related to staphylococcal virulence were used to monitor the effects of antibiotics on gene expression in a disc diffusion assay. The selected genes were hla and spa encoding -hemolysin and Protein A, respectively and RNAIII, the effector molecule of the agr quorum sensing system. The results were confirmed by quantitative real-time PCR. Additionally, we monitored the effect of subinhibitory concentrations of antibiotics on the ability of S. aureus to form biofilm in a microtiter plate assay. The results show that sub-lethal antibiotic concentrations diversely modulate expression of RNAIII, hla and spa. Consistently, expression of all three genes were repressed by aminoglycosides and induced by fluoroquinolones and penicillins. In contrast, the -lactam sub-group cephalosporins enhanced expression of RNAIII and hla but diversely affected expression of spa. The compounds cefalotin, cefamandole, cefoxitin, ceftazidime and cefixine were found to up-regulate spa, while down-regulation was observed for cefuroxime, cefotaxime and cefepime. Interestingly, biofilm assays demonstrated that the spa-inducing cefalotin resulted in less biofilm formation compared to the spa-repressing cefotaxime. Conclusions: We find that independently of the cephalosporin generation, cephalosporins oppositely regulate spa expression and biofilm formation. Repression of spa expression correlates with the presence of a distinct methyloxime group while induction correlates with an acidic substituted oxime group. As cephalosporines target the cell wall penicillin binding proteins we speculate that subtle differences in this interaction fine-tunes spa expression independently of agr. {\circledC} 2012 Nielsen et al.; licensee BioMed Central Ltd.",
keywords = "Biochemistry, Genetics and Molecular Biology (all), Medicine (all), Antibiotics, Biofilm formation, Protein A (spa), Staphylococcus aureus, Subinhibitory concentrations, Virulence, antiinfective agent, bacterial protein, DNA directed RNA polymerase III, article, cell wall, drug effect, genetic transcription, genetics, metabolism, microbial sensitivity test, real time polymerase chain reaction, reverse transcription polymerase chain reaction, Anti-Bacterial Agents, Bacterial Proteins, Cell Wall, Microbial Sensitivity Tests, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, RNA Polymerase III, Transcription, Genetic, BACTERIAL cell walls",
author = "Nielsen, {Lene N{\o}rby} and Michael Roggenbuck and Jakob Haaber and Dan Ifrah and Hanne Ingmer",
year = "2012",
doi = "10.1186/1756-0500-5-457",
language = "English",
volume = "5",
journal = "BMC Research Notes",
issn = "1756-0500",
publisher = "BioMed Central Ltd.",
number = "1",

}

RIS

TY - JOUR

T1 - Diverse modulation of spa transcription by cell wall active antibiotics in Staphylococcus aureus

AU - Nielsen, Lene Nørby

AU - Roggenbuck, Michael

AU - Haaber, Jakob

AU - Ifrah, Dan

AU - Ingmer, Hanne

PY - 2012

Y1 - 2012

N2 - Abstract. Background: The aim of this study was to investigate the effect of various classes of clinically relevant antibiotics at sub-lethal concentrations on virulence gene expression and biofilm formation in Staphylococcus aureus. Findings. LacZ promoter fusions of genes related to staphylococcal virulence were used to monitor the effects of antibiotics on gene expression in a disc diffusion assay. The selected genes were hla and spa encoding -hemolysin and Protein A, respectively and RNAIII, the effector molecule of the agr quorum sensing system. The results were confirmed by quantitative real-time PCR. Additionally, we monitored the effect of subinhibitory concentrations of antibiotics on the ability of S. aureus to form biofilm in a microtiter plate assay. The results show that sub-lethal antibiotic concentrations diversely modulate expression of RNAIII, hla and spa. Consistently, expression of all three genes were repressed by aminoglycosides and induced by fluoroquinolones and penicillins. In contrast, the -lactam sub-group cephalosporins enhanced expression of RNAIII and hla but diversely affected expression of spa. The compounds cefalotin, cefamandole, cefoxitin, ceftazidime and cefixine were found to up-regulate spa, while down-regulation was observed for cefuroxime, cefotaxime and cefepime. Interestingly, biofilm assays demonstrated that the spa-inducing cefalotin resulted in less biofilm formation compared to the spa-repressing cefotaxime. Conclusions: We find that independently of the cephalosporin generation, cephalosporins oppositely regulate spa expression and biofilm formation. Repression of spa expression correlates with the presence of a distinct methyloxime group while induction correlates with an acidic substituted oxime group. As cephalosporines target the cell wall penicillin binding proteins we speculate that subtle differences in this interaction fine-tunes spa expression independently of agr. © 2012 Nielsen et al.; licensee BioMed Central Ltd.

AB - Abstract. Background: The aim of this study was to investigate the effect of various classes of clinically relevant antibiotics at sub-lethal concentrations on virulence gene expression and biofilm formation in Staphylococcus aureus. Findings. LacZ promoter fusions of genes related to staphylococcal virulence were used to monitor the effects of antibiotics on gene expression in a disc diffusion assay. The selected genes were hla and spa encoding -hemolysin and Protein A, respectively and RNAIII, the effector molecule of the agr quorum sensing system. The results were confirmed by quantitative real-time PCR. Additionally, we monitored the effect of subinhibitory concentrations of antibiotics on the ability of S. aureus to form biofilm in a microtiter plate assay. The results show that sub-lethal antibiotic concentrations diversely modulate expression of RNAIII, hla and spa. Consistently, expression of all three genes were repressed by aminoglycosides and induced by fluoroquinolones and penicillins. In contrast, the -lactam sub-group cephalosporins enhanced expression of RNAIII and hla but diversely affected expression of spa. The compounds cefalotin, cefamandole, cefoxitin, ceftazidime and cefixine were found to up-regulate spa, while down-regulation was observed for cefuroxime, cefotaxime and cefepime. Interestingly, biofilm assays demonstrated that the spa-inducing cefalotin resulted in less biofilm formation compared to the spa-repressing cefotaxime. Conclusions: We find that independently of the cephalosporin generation, cephalosporins oppositely regulate spa expression and biofilm formation. Repression of spa expression correlates with the presence of a distinct methyloxime group while induction correlates with an acidic substituted oxime group. As cephalosporines target the cell wall penicillin binding proteins we speculate that subtle differences in this interaction fine-tunes spa expression independently of agr. © 2012 Nielsen et al.; licensee BioMed Central Ltd.

KW - Biochemistry, Genetics and Molecular Biology (all)

KW - Medicine (all)

KW - Antibiotics

KW - Biofilm formation

KW - Protein A (spa)

KW - Staphylococcus aureus

KW - Subinhibitory concentrations

KW - Virulence

KW - antiinfective agent

KW - bacterial protein

KW - DNA directed RNA polymerase III

KW - article

KW - cell wall

KW - drug effect

KW - genetic transcription

KW - genetics

KW - metabolism

KW - microbial sensitivity test

KW - real time polymerase chain reaction

KW - reverse transcription polymerase chain reaction

KW - Anti-Bacterial Agents

KW - Bacterial Proteins

KW - Cell Wall

KW - Microbial Sensitivity Tests

KW - Real-Time Polymerase Chain Reaction

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - RNA Polymerase III

KW - Transcription, Genetic

KW - BACTERIAL cell walls

U2 - 10.1186/1756-0500-5-457

DO - 10.1186/1756-0500-5-457

M3 - Journal article

VL - 5

JO - BMC Research Notes

JF - BMC Research Notes

SN - 1756-0500

IS - 1

M1 - 457

ER -