Characterization of the Staphylococcus aureus Heat Shock, Cold Shock, Stringent, and SOS Responses and Their Effects on Log-Phase mRNA Turnover

ABSTRACT Despite its being a leading cause of nosocomal and community-acquired infections, surprisingly little is known about Staphylococcus aureus stress responses. In the current study, Affymetrix S. aureus GeneChips were used to define transcriptome changes in response to cold shock, heat shock, stringent, and SOS response-inducing conditions. Additionally, the RNA turnover properties of each response were measured. Each stress response induced distinct biological processes, subsets of virulence factors, and antibiotic determinants. The results were validated by real-time PCR and stress-mediated changes in antimicrobial agent susceptibility. Collectively, many S. aureus stress-responsive functions are conserved across bacteria, whereas others are unique to the organism. Sets of small stable RNA molecules with no open reading frames were also components of each response. Induction of the stringent, cold shock, and heat shock responses dramatically stabilized most mRNA species. Correlations between mRNA turnover properties and transcript titers suggest that S. aureus stress response-dependent alterations in transcript abundances can, in part, be attributed to alterations in RNA stability. This phenomenon was not observed within SOS-responsive cells.

[1]  P. Riley CORRECTION , 2006, Journal of Clinical Pathology.

[2]  R. Overbeek,et al.  Characterizing the Effect of the Staphylococcus aureus Virulence Factor Regulator, SarA, on Log-Phase mRNA Half-Lives , 2006, Journal of bacteriology.

[3]  Susana Campoy,et al.  β-Lactam Antibiotics Induce the SOS Response and Horizontal Transfer of Virulence Factors in Staphylococcus aureus , 2006, Journal of bacteriology.

[4]  W. Bentley,et al.  Global Transcriptome Analysis of Staphylococcus aureus Response to Hydrogen Peroxide , 2006, Journal of bacteriology.

[5]  T. Bagnyukova,et al.  Hydrogen peroxide increases the activities of soxRS regulon enzymes and the levels of oxidized proteins and lipids in Escherichia coli , 2005, Cell biology international.

[6]  Thomas J. Begley,et al.  Genome-wide responses to DNA-damaging agents. , 2005, Annual review of microbiology.

[7]  S. Gottesman Micros for microbes: non-coding regulatory RNAs in bacteria. , 2005, Trends in genetics : TIG.

[8]  C. Ubeda,et al.  Antibiotic‐induced SOS response promotes horizontal dissemination of pathogenicity island‐encoded virulence factors in staphylococci , 2005, Molecular microbiology.

[9]  P. Bradford,et al.  A Novel MATE Family Efflux Pump Contributes to the Reduced Susceptibility of Laboratory-Derived Staphylococcus aureus Mutants to Tigecycline , 2005, Antimicrobial Agents and Chemotherapy.

[10]  G. Kaatz,et al.  Multidrug Resistance in Staphylococcus aureus Due to Overexpression of a Novel Multidrug and Toxin Extrusion (MATE) Transport Protein , 2005, Antimicrobial Agents and Chemotherapy.

[11]  M. Tomasz,et al.  DNA adduct of the mitomycin C metabolite 2,7-diaminomitosene is a nontoxic and nonmutagenic DNA lesion in vitro and in vivo. , 2005, Chemical research in toxicology.

[12]  M. Smeltzer,et al.  Comparative Genomics of Staphylococcus aureus Musculoskeletal Isolates , 2005, Journal of bacteriology.

[13]  Philip Hill,et al.  Clp ATPases are required for stress tolerance, intracellular replication and biofilm formation in Staphylococcus aureus , 2004, Molecular microbiology.

[14]  S. Gottesman The small RNA regulators of Escherichia coli: roles and mechanisms*. , 2004, Annual review of microbiology.

[15]  M. Smeltzer,et al.  Global Gene Expression in Staphylococcus aureus Biofilms , 2004, Journal of bacteriology.

[16]  N. Wingreen,et al.  The Small RNA Chaperone Hfq and Multiple Small RNAs Control Quorum Sensing in Vibrio harveyi and Vibrio cholerae , 2004, Cell.

[17]  Daphne Macapagal,et al.  Microarray-Based Analysis of the Staphylococcus aureus σB Regulon , 2004 .

[18]  S. Gottesman,et al.  Identification of tandem duplicate regulatory small RNAs in Pseudomonas aeruginosa involved in iron homeostasis. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[19]  H. Monteil,et al.  Regulation of virulence determinants in Staphylococcus aureus: complexity and applications. , 2004, FEMS microbiology reviews.

[20]  J. Sabina,et al.  Interfering with Different Steps of Protein SynthesisExplored by Transcriptional Profiling of Escherichia coliK-12 , 2003, Journal of bacteriology.

[21]  B. Bukau,et al.  Small heat shock proteins, ClpB and the DnaK system form a functional triade in reversing protein aggregation , 2003, Molecular microbiology.

[22]  M. Smeltzer,et al.  Mutation of sarA in Staphylococcus aureus Limits Biofilm Formation , 2003, Infection and Immunity.

[23]  R. Novick Autoinduction and signal transduction in the regulation of staphylococcal virulence , 2003, Molecular microbiology.

[24]  G. Church,et al.  Global RNA half-life analysis in Escherichia coli reveals positional patterns of transcript degradation. , 2003, Genome research.

[25]  M. Smeltzer,et al.  Role of sarA in the Pathogenesis of Staphylococcus aureus Musculoskeletal Infection , 2003, Infection and Immunity.

[26]  S. Rockwell,et al.  Relative toxicities of DNA cross-links and monoadducts: new insights from studies of decarbamoyl mitomycin C and mitomycin C. , 2002, Chemical research in toxicology.

[27]  K. Wassarman Small RNAs in Bacteria Diverse Regulators of Gene Expression in Response to Environmental Changes , 2002, Cell.

[28]  R. Woodgate,et al.  Roles of DNA polymerases V and II in SOS-induced error-prone and error-free repair in Escherichia coli , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[29]  R. Woodgate,et al.  Identification of mucAB-like homologs on two IncT plasmids, R394 and Rts-1. , 2000, Mutation research.

[30]  R. England,et al.  Accumulation of ppGpp and ppGp in Staphylococcus aureus 8325‐4 following nutrient starvation , 2000, Letters in applied microbiology.

[31]  S. Kjelleberg,et al.  The role of RNA stability during bacterial stress responses and starvation. , 2000, Environmental microbiology.

[32]  P. Forterre,et al.  DNA topology and the thermal stress response, a tale from mesophiles and hyperthermophiles. , 2000, BioEssays : news and reviews in molecular, cellular and developmental biology.

[33]  Kenneth W. Bayles,et al.  The Staphylococcus aureus lrgAB Operon Modulates Murein Hydrolase Activity and Penicillin Tolerance , 2000, Journal of bacteriology.

[34]  S. Rüdiger,et al.  Identification of thermolabile Escherichia coli proteins: prevention and reversion of aggregation by DnaK and ClpB , 1999, The EMBO journal.

[35]  P. Hanawalt,et al.  A phylogenomic study of DNA repair genes, proteins, and processes. , 1999, Mutation research.

[36]  A. Zvi,et al.  Sequential mechanism of solubilization and refolding of stable protein aggregates by a bichaperone network. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[37]  M. Inouye,et al.  Sequence‐selective interactions with RNA by CspB, CspC and CspE, members of the CspA family of Escherichia coli , 1999, Molecular microbiology.

[38]  S. Mazmanian,et al.  Staphylococcus aureus sortase, an enzyme that anchors surface proteins to the cell wall. , 1999, Science.

[39]  G. Rapoport,et al.  CtsR, a novel regulator of stress and heat shock response, controls clp and molecular chaperone gene expression in Gram‐positive bacteria , 1999, Molecular microbiology.

[40]  L. Piddock,et al.  Accumulation of rifampicin by Escherichia coli and Staphylococcus aureus. , 1998, The Journal of antimicrobial chemotherapy.

[41]  G. Storz,et al.  A Small, Stable RNA Induced by Oxidative Stress: Role as a Pleiotropic Regulator and Antimutator , 1997, Cell.

[42]  M. Inouye,et al.  CspA, the Major Cold-shock Protein of Escherichia coli, Is an RNA Chaperone* , 1997, The Journal of Biological Chemistry.

[43]  M. Inouye,et al.  Promoter‐independent cold‐shock induction of cspA and its derepression at 37°C by mRNA stabilization , 1997 .

[44]  S. Gottesman,et al.  The small RNA, DsrA, is essential for the low temperature expression of RpoS during exponential growth in Escherichia coli. , 1996, The EMBO journal.

[45]  F. Baneyx,et al.  Recombinant protein expression at low temperatures under the transcriptional control of the major Escherichia coli cold shock promoter cspA , 1996, Applied and environmental microbiology.

[46]  M. Inouye,et al.  Cold shock induces a major ribosomal-associated protein that unwinds double-stranded RNA in Escherichia coli. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[47]  D. Knowles,et al.  Occurrence of the regulatory nucleotides ppGpp and pppGpp following induction of the stringent response in staphylococci , 1995, Journal of bacteriology.

[48]  M. Tomasz,et al.  Mitomycin C: small, fast and deadly (but very selective). , 1995, Chemistry & biology.

[49]  E. Snyder,et al.  High-affinity RNA ligands to Escherichia coli ribosomes and ribosomal protein S1: comparison of natural and unnatural binding sites. , 1995, Biochemistry.

[50]  K. Ubukata,et al.  Nucleotide sequence and characterization of the Staphylococcus aureus norA gene, which confers resistance to quinolones , 1990, Journal of bacteriology.

[51]  F. Neidhardt,et al.  Escherichia Coli and Salmonella: Typhimurium Cellular and Molecular Biology , 1987 .

[52]  J. Collins,et al.  Posttranscriptional control of Klebsiella pneumoniae nif mRNA stability by the nifL product , 1986, Journal of bacteriology.

[53]  D. Kahn,et al.  Metabolic control of Klebsiella pneumoniae mRNA degradation by the availability of fixed nitrogen. , 1982, Journal of general microbiology.

[54]  L. Strausbaugh,et al.  Regulation of the Escherichia coli K-12 uvrB operon , 1982, Journal of bacteriology.

[55]  H. Hennecke,et al.  Regulation of nitrogenase messenger RNA synthesis and stability in Klebsiella pneumoniae , 1981, Archives of Microbiology.

[56]  D. Mount,et al.  Cleavage of the Escherichia coli lexA protein by the recA protease. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[57]  P. Dennis,et al.  Regulation of ribosomal and transfer RNA synthesis by guanosine 5'-diphosphate-3'-monophosphate. , 1980, The Journal of biological chemistry.

[58]  D. Mount,et al.  Identification of the recA (tif) gene product of Escherichia coli. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[59]  B. Ames,et al.  Guanosine 5'-diphosphate 3'-diphosphate (ppGpp): positive effector for histidine operon transcription and general signal for amino-acid deficiency. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[60]  Adeline R. Whitney,et al.  Insights into Mechanisms Used by Staphylococcus aureus to Avoid Destruction by Human Neutrophils , 2005 .

[61]  Thomas Egli,et al.  Molecular components of physiological stress responses in Escherichia coli. , 2004, Advances in biochemical engineering/biotechnology.

[62]  M. Bischoff,et al.  Microarray-based analysis of the Staphylococcus aureus sigmaB regulon. , 2004, Journal of bacteriology.

[63]  S. Engelmann,et al.  s B Activity Depends on RsbU in Staphylococcus aureus , 2001 .

[64]  A EisenJ,et al.  DNA修復遺伝子,タンパクと過程のphylogenomic(系統発生的ゲノム)調査 , 1999 .

[65]  M. Inouye,et al.  Promoter-independent cold-shock induction of cspA and its derepression at 37 degrees C by mRNA stabilization. , 1997, Molecular microbiology.

[66]  M. Inouye,et al.  Major cold shock protein of Escherichia coli. , 1990, Proceedings of the National Academy of Sciences of the United States of America.