β-Lactam Antibiotics Induce the SOS Response and Horizontal Transfer of Virulence Factors in<i>Staphylococcus aureus</i>

Maiques, Elisa; Úbeda, Carles; Campoy, Susana; Salvador, Noelia; Lasa, Íñigo; Novick, Richard P.; Barbé, Jordi; Penadés, José R.

doi:10.1128/jb.188.7.2726-2729.2006

Cited by 295 publications

(226 citation statements)

References 20 publications

(28 reference statements)

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“…3a; Cirz et al, 2007). When comparing S. aureus LexA with those of other organisms, a conserved auto-proteolytic cleavage site is present at amino acid sequence Ala93-Gly94 (Maiques et al, 2006) corresponding to a LexA NTD of 10.5 kDa and a CTD of 12.8 kDa. Thus, the appearance of a 13 kDa fragment after MMC treatment suggests that only the CTD is visible in wild-type cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The SOS regulated genes carry out diverse functions in response to DNA damage such as nucleotide excision repair, translesion DNA replication, homologous recombination and cell division arrest. Of importance to bacterial pathogens, the SOS response also modulates the dissemination of mobile genetic elements expressing antibiotic resistance and virulence factors (Beaber et al, 2004;Maiques et al, 2006;Ú beda et al, 2005). In addition, it is well known that several groups of antibiotics are in fact inducers of the SOS response such as the fluoroquinolones (Cirz et al, 2005;Mesak et al, 2008), trimethoprim (Lewin & Amyes, 1991) and b-lactams (Maiques et al, 2006;Miller et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Clp-dependent proteolysis of the LexA N-terminal domain in Staphylococcus aureus

et al. 2011

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The SOS response is governed by the transcriptional regulator LexA and is elicited in many bacterial species in response to DNA damaging conditions. Induction of the SOS response is mediated by autocleavage of the LexA repressor resulting in a C-terminal dimerization domain (CTD) and an N-terminal DNA-binding domain (NTD) known to retain some DNA-binding activity. The proteases responsible for degrading the LexA domains have been identified in Escherichia coli as ClpXP and Lon. Here, we show that in the human and animal pathogen Staphylococcus aureus, the ClpXP and ClpCP proteases contribute to degradation of the NTD and to a lesser degree the CTD. In the absence of the proteolytic subunit, ClpP, or one or both of the Clp ATPases, ClpX and ClpC, the LexA domains were stabilized after autocleavage. Production of a stabilized variant of the NTD interfered with mitomycin-mediated induction of sosA expression while leaving lexA unaffected, and also significantly reduced SOS-induced mutagenesis. Our results show that sequential proteolysis of LexA is conserved in S. aureus and that the NTD may differentially regulate a subset of genes in the SOS regulon.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clp-dependent proteolysis of the LexA N-terminal domain in Staphylococcus aureus

et al. 2011

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“…3D) and pathogenicity island genes. The concerted functions of these factors may account, in part, for the observation that SOS induction results in phage-mediated pathogenicity island dissemination among staphylococci (34,55). Striking features were observed within S. aureus stringent response-induced cells.…”

Section: Discussionmentioning

confidence: 98%

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

et al. 2006

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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 responseinducing 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.

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“…For S. aureus it could also be demonstrated that there is a link between induction of prophages and subsequent virulence modulation of the bacterium by antibiotics which are often used during the treatment of infections (Goerke et al, 2006a). A positive effect of blactam antibiotics on phage replication was recently described (Maiques et al, 2006). Subinhibitory concentrations of nafcillin (Stevens et al, 2007) and oxacillin (Dumitrescu et al, 2007) were found to enhance PVL expression, which is thought to contribute to worse outcomes of S. aureus infections after antibiotic therapy.…”

Section: Discussionmentioning

confidence: 99%

Transcription of the phage-encoded Panton–Valentine leukocidin of Staphylococcus aureus is dependent on the phage life-cycle and on the host background

et al. 2009

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Panton-Valentine leukocidin (PVL) is a pore-forming, bi-component toxin secreted by Staphylococcus aureus strains epidemiologically associated with diseases such as necrotizing pneumonia and skin and soft-tissue infections. Here we demonstrate that transcription of the phage-encoded PVL (encoded in the luk-PV operon) is dependent on two major determinants: the phage life-cycle and the host chromosomal background. Mitomycin C induction of PVLencoding prophages from different community-acquired MRSA strains led to an increase in the amount of luk-PV mRNA as a result of read-through transcription from latent phage promoters and an increase in phage copy numbers. Failing prophage excision was reflected in a constant expression of luk-PV as in the case of strain USA300, suggesting that wSa2USA300 is a replication-defective prophage. Additionally, we could show that luk-PV transcription is influenced by the S. aureus global virulence regulators agr and sae. We found a strong impact of the host background on prophage induction and replication when analysing PVL phages in different S. aureus strains. For example phage wSa2mw was greatly induced by mitomycin C in its native host MW2 and in strain Newman but to a considerably lesser extent in strains 8325-4, RN6390 and ISP479c. This discrepancy was not linked to the SOS response of the bacteria since recA transcription did not vary between the strains. These results suggest a fine tuning between certain phages and their host, with major impact on the expression of phage-encoded virulence genes. INTRODUCTIONStaphylococcus aureus causes a variety of local and systemic infections in humans and is one of the most important community-acquired and nosocomial pathogens. The versatility of this bacterium is due to its ability to produce a wide range of surface-exposed molecules which mediate interaction with the host cell, as well as several secreted virulence factors. S. aureus necrotizing pneumonia and skin and soft-tissue infections, which can also affect young, immunocompetent persons, is described as a threat associated with community-acquired (ca)MRSA and MSSA strains bearing the Panton-Valentine leukocidin (PVL) genes (Diederen & Kluytmans, 2006;Gillet et al., 2002;Vandenesch et al., 2003). The possible contribution of PVL to the virulence of S. aureus has been argued in studies using a variety of different animal models (Bubeck Wardenburg et al., 2008;Diep & Otto, 2008; LabandeiraRey et al., 2007;Montgomery et al., 2008;Voyich et al., 2006;Wang et al., 2007). PVL is a bi-component, poreforming cytotoxin that targets host defence cells such as human polymorphonuclear neutrophils, monocytes and macrophages (Genestier et al., 2005;Kaneko & Kamio, 2004;Prevost et al., 1995). The active form of PVL requires the assembly of two polypeptides, LukS-PV and LukF-PV, for which the corresponding genes (lukS-PV, lukF-PV) are carried by a prophage.Although tightly linked to the phage genome and dependent on it for horizontal transfer, most of the phage-encoded virulence factors are i...

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β-Lactam Antibiotics Induce the SOS Response and Horizontal Transfer of Virulence Factors inStaphylococcus aureus

Cited by 295 publications

References 20 publications

Clp-dependent proteolysis of the LexA N-terminal domain in Staphylococcus aureus

Clp-dependent proteolysis of the LexA N-terminal domain in Staphylococcus aureus

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

Transcription of the phage-encoded Panton–Valentine leukocidin of Staphylococcus aureus is dependent on the phage life-cycle and on the host background

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