The acid response network of Staphylococcus aureus.
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ABSTRACT:
SUBMITTER: Zhou C
PROVIDER: S-EPMC7311314 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Genome-wide transcriptional profiling studies of the growth of bacteria with antimicrobial agents often reveals aspects of the drug-specific protective bacterial response. Fusidic acid is a steroid antimicrobial that inhibits protein synthesis by interfering with the release of elongation factor G (EF-G) after it has functioned in the translocation step. Two hundred and seventy two genes were both up- and down-regulated in a fusidic acid-susceptible strain of Staphylococcus aureus following challenge with 2 mg/L-1 fusidic acid for 15 min. Many genes altered by fusidic acid challenge are associated with protein synthesis such as fusA, which encodes EF-G which was up-regulated following exposure to the drug. The Staphylococcus microarray meta-database which curates and compares S. aureus transcriptome data revealed that the fusidic acid stimulon has the greatest overlap with the S. aureus cold shock- and stringent-responses. Six out of 9 autolysin genes making up the two component YycFG regulon (ssaA1-ssaA4, isaA and sceD) were also upregulated by fusidic acid; as were a carboxylesterase (est) and two putative Emr-Qac-like multidrug efflux pumps (emr-qac1 and emr-qac2). Genes down-regulated by fusidic acid induction encode a putative secreted acid phosphatase (sapS) and a number of protease genes (yjbG1, yjbG2, htrA1 and htrA2). Transcriptional analysis in conjunction with mutant fusidic acid susceptibility experiments revealed that th45 e virulence gene regulatory agr operon, a YycFG controlled peptidoglycan hydrolase gene isaA and the proteases htrA1 and htrA2 are required for the expression of wild-type levels of fusidic acid susceptibility.
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Project description: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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Project description:It is well established that bacteria are able to respond to temporal gradients (e.g., by chemotaxis). However, it is widely held that prokaryotes are too small to sense spatial gradients. This contradicts the common observation that the vast majority of bacteria live on the surface of a solid substrate (e.g., as a biofilm). Herein we report direct experimental evidence that the nonmotile bacterium Staphylococcus aureus possesses a tactile response, or primitive sense of touch, that allows it to respond to spatial gradients. Attached cells recognize their substrate interface and localize adhesins toward that region. Braille-like avidity maps reflect a cell's biochemical sensory response and reveal ultrastructural regions defined by the actual binding activity of specific proteins.
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Project description:Staphylococcus aureus causes acute and chronic infections resulting in significant morbidity. Urease, an enzyme that generates NH3 and CO2 from urea, is key to pH homeostasis in bacterial pathogens under acidic stress and nitrogen limitation. However, the function of urease in S. aureus niche colonization and nitrogen metabolism has not been extensively studied. We discovered that urease is essential for pH homeostasis and viability in urea-rich environments under weak acid stress. The regulation of urease transcription by CcpA, Agr, and CodY was identified in this study, implying a complex network that controls urease expression in response to changes in metabolic flux. In addition, it was determined that the endogenous urea derived from arginine is not a significant contributor to the intracellular nitrogen pool in non-acidic conditions. Furthermore, we found that during a murine chronic renal infection, urease facilitates S. aureus persistence by promoting bacterial fitness in the low-pH, urea-rich kidney. Overall, our study establishes that urease in S. aureus is not only a primary component of the acid response network but also an important factor required for persistent murine renal infections.
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