Regulatory Adaptation of Staphylococcus aureus during Nasal Colonization of Humans

Burian, Marc; Wolz, Christiane; Goerke, Christiane

doi:10.1371/journal.pone.0010040

Cited by 105 publications

(186 citation statements)

References 51 publications

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“…The temporal expression patterns of spa have been shown to be highly strain variable, especially during post-exponential growth phases, with transcription decreasing significantly in some backgrounds while remaining much more stable in others (10). In CHE482, spa transcription increased steadily throughout exponential growth and decreased only slightly thereafter.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Profiling of XdrA, a New Regulator ofspaTranscription inStaphylococcus aureus

et al. 2010

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Transcription of spa, encoding the virulence factor protein A in Staphylococcus aureus, is tightly controlled by a complex regulatory network, ensuring its temporal expression over growth and at appropriate stages of the infection process. Transcriptomic profiling of XdrA, a DNA-binding protein that is conserved in all S. aureus genomes and shares similarity with the XRE family of helix-turn-helix, antitoxin-like proteins, revealed it to be a previously unidentified activator of spa transcription. To assess how XdrA fits into the complex web of spa regulation, a series of regulatory mutants were constructed; consisting of single, double, triple, and quadruple mutants lacking XdrA and/or the three key regulators previously shown to influence spa transcription directly (SarS, SarA, and RNAIII). A series of lacZ reporter gene fusions containing nested deletions of the spa promoter identified regions influenced by XdrA and the other three regulators. XdrA had almost as strong an activating effect on spa as SarS and acted on the same spa operator regions as SarS, or closely overlapping regions. All data from microarrays, Northern and Western blot analyses, and reporter gene fusion experiments indicated that XdrA is a major activator of spa expression that appears to act directly on the spa promoter and not through previously characterized regulators.

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Section: Discussionmentioning

confidence: 99%

Transcriptional Profiling of XdrA, a New Regulator ofspaTranscription inStaphylococcus aureus

et al. 2010

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“…However, the precise roles of most of these virulence factors during colonization and pathogenesis in humans have remained largely unclear, as determination of in vivo expression of bacterial virulence factors is technically challenging. Burian et al showed by a quantitative PCR (qPCR) analysis on samples from 4 persistent nasal carriers that the adhesin genes clfB, fnbA, and isdA and the immune modulator gene chp are expressed in vivo (25). In an artificial inoculation study, clfB proved to be essential for colonization in humans (26).…”

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confidence: 99%

IgG4 Subclass-Specific Responses to Staphylococcus aureus Antigens Shed New Light on Host-Pathogen Interaction

et al. 2015

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f IgG4 responses are considered indicative for long-term or repeated exposure to particular antigens. Therefore, studying IgG4-specific antibody responses against Staphylococcus aureus might generate new insights into the respective host-pathogen interactions and the microbial virulence factors involved. Using a bead-based flow cytometry assay, we determined total IgG (IgGt), IgG1, and IgG4 antibody responses to 40 different S. aureus virulence factors in sera from healthy persistent nasal carriers, healthy persistent noncarriers, and patients with various staphylococcal infections from three distinct countries. IgGt responses were detected against all tested antigens. These were mostly IgG1 responses. In contrast, IgG4 antibodies were detected to alphatoxin, chemotaxis inhibitory protein of S. aureus (CHIPS), exfoliative toxins A and B (ETA and -B), HlgB, IsdA, LukD, -E, -F, and -S, staphylococcal complement inhibitor (SCIN), staphylococcal enterotoxin C (SEC), staphylococcal superantigen-like proteins 1, 3, 5, and 9 (SSL1, -3, -5, and -9), and toxic shock syndrome toxin 1 (TSST-1) only. Large interpatient variability was observed, and the type of infection or geographical location did not reveal conserved patterns of response. As persistent S. aureus carriers trended toward IgG4 responses to a larger number of antigens than persistent noncarriers, we also investigated sera from patients with epidermolysis bullosa (EB), a genetic blistering disease associated with high S. aureus carriage rates. EB patients responded immunologically to significantly more antigens than noncarriers and trended toward even more responses than carriers. Altogether, we conclude that the IgG4 responses against a restricted panel of staphylococcal antigens consisting primarily of immune modulators and particular toxins indicate important roles for these virulence factors in staphylococcal pathogen-host interactions, such as chronicity of colonization and/or (subclinical) infections.

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“…While the pathogenic roles of many S. aureus secreted factors and surface proteins have been extensively studied, the physiology of this commensal in the colonization state and other host environments has received only limited attention (12,13). Sialic acid (N-acetylneuraminic acid [Neu5Ac]) is one example of a bioavailable energy source present in many host niches (14).…”

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Sialic Acid Catabolism in Staphylococcus aureus

et al. 2013

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Staphylococcus aureus is a ubiquitous bacterial pathogen that is the causative agent of numerous acute and chronic infections. S. aureus colonizes the anterior nares of a significant portion of the healthy adult population, but the mechanisms of colonization remain incompletely defined. Sialic acid (N-acetylneuraminic acid [Neu5Ac]) is a bioavailable carbon and nitrogen source that is abundant on mucosal surfaces and in secretions in the commensal environment. Our findings demonstrate that Neu5Ac can serve as an S. aureus carbon source, and we have identified a previously uncharacterized chromosomal locus (nan) that is required for Neu5Ac utilization. Molecular characterization of the nan locus indicates that it contains five genes, organized into four transcripts, and the genes were renamed nanE, nanR, nanK, nanA, and nanT. Initial studies with gene deletions indicate that nanT, predicted to encode the Neu5Ac transporter, and nanA and nanE, predicted to encode catabolic enzymes, are essential for growth on Neu5Ac. Furthermore, a nanE deletion mutant exhibits a growth inhibition phenotype in the presence of Neu5Ac. Transcriptional fusions and Northern blot analyses indicate that NanR represses the expression of both the nanAT and nanE transcripts, which can be relieved with Neu5Ac. Electrophoretic mobility studies demonstrate that NanR binds to the nanAT and nanE promoter regions, and the Neu5Ac catabolic intermediate N-acetylmannosamine-6-phosphate (ManNAc-6P) relieves NanR promoter binding. Taken together, these data indicate that the nan gene cluster is essential for Neu5Ac utilization and may perform an important function for S. aureus survival in the host.

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Regulatory Adaptation of Staphylococcus aureus during Nasal Colonization of Humans

Cited by 105 publications

References 51 publications

Transcriptional Profiling of XdrA, a New Regulator ofspaTranscription inStaphylococcus aureus

Transcriptional Profiling of XdrA, a New Regulator ofspaTranscription inStaphylococcus aureus

IgG4 Subclass-Specific Responses to Staphylococcus aureus Antigens Shed New Light on Host-Pathogen Interaction

Sialic Acid Catabolism in Staphylococcus aureus

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