The acid response network of Staphylococcus aureus.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhou C
PROVIDER: S-EPMC7311314 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
Publications
The acid response network of Staphylococcus aureus.
Current opinion in microbiology 20200429
Staphylococcus aureus colonizes or causes infection in a multitude of niches within a mammalian host. Many of these niches are acidic, yet specific pH resistance mechanisms that facilitate survival have not been thoroughly investigated. This review discusses recent studies documenting known acid resistance mechanisms in S. aureus and other staphylococcal species. However, studies that clearly define the regulation of the acid resistance regulon and potential interactions with weak organic acids ...[more]
Similar Datasets
Project description:In the present study, we employed Affymetrix Staphylococcus aureus GeneChip arrays to investigate the dynamics of global gene expression profiles during the cellular response of Staphylococcus aureus to peracetic acid, which involved initial growth inhibition and subsequent partial recovery. Keywords: Time course
2006-05-31 | GSE4184 | GEO
Project description:Staphylococcus aureus Newman and Staphylococcus epidermidis Tu3298, 20 minutes post challenge with sub-inhibitory concentration of sapienic acid vs equivalent concentration of ethanol. Challenge was added at mid logarithmic growth (OD600 0.5). Biological triplicates of samples were sequenced.
2016-07-31 | E-MTAB-4587 | biostudies-arrayexpress
Project description:We present a general overview of the changes in the genetic expression along a time curve through the first 20 minutes after acidification to pH 4.5 of exponentially growing cultures of the food pathogenic strain Staphylococcus aureus 50583. A newly developed method for statistical significance testing was used to detect significant gene expression responses. Most responses showed an increase or decrease from time zero to 10 minutes after acidification and then generally a stabilisation in expression level from 10 to 20 min. Increased urease activity appeared to be an important factor in the acid defence along with proton excretion by NADH dehydrogenase and macromolecule repair mechanisms. Oxidative stress responses such as increased expression of thioredoxin genes and upregulation of pentose phosphate pathway genes to generate more reducing power were also induced. A general reduction in the expression of genes encoding ribosomal proteins and genes involved in nucleotide synthesis as well as fatty acid and lipoprotein metabolism reflected the lowered growth rate after acidification. The pH shock did not appear to trigger major virulence responses or biofilm formation. The metal ion regulation and transport was affected by the acid shock and production of several cofactors such as molybdopterin was increased. Many of the presented observations could be explained, while some represent still unknown mechanisms. The patterns of regulation were confirmed by real time reverse transcriptase PCR. Together these results showed the main responses of S. aureus and will be a good starting point for future more specific in-depth studies of specific gene responses in conjunction with acid stress defence of S. aureus. Keywords: Time course, stress response
2007-07-29 | GSE7273 | GEO
Project description:Staphylococcus aureus is capable of phosphorylating exogenous fatty acids for incorporation into the bacterium's membrane via the fatty acid kinase, FakA. Additionally, FakA plays a significant role in virulence factor regulation and skin infections. We previously showed that a fakA mutant displays altered growth kinetics in vitro, observed during the late-exponential phase of growth. Here, we demonstrate that the absence of FakA leads to key metabolic changes. First, the fakA mutant has an altered acetate metabolism, with acetate being consumed at an increased rate than in the wild-type strain. Moreover, the growth benefit was diminished with inactivation of the acetate-generating enzyme AckA. Using a mass spectrometry-based approach, we identified altered concentrations of tricarboxylic acid (TCA) cycle intermediates and both intracellular and extracellular amino acids. Together, these data demonstrate a change in carbohydrate carbon utilization and altered amino acid metabolism in the fakA mutant. Energy status analysis revealed the mutant had a similar ADP/ATP ratio to that of the wild type, but a reduced adenylate energy charge. The inactivation of fakA changed the NAD+/NADH and NADP+/NADPH ratios, indicating a more oxidized cellular environment. Evidence points to the global metabolic regulatory proteins CcpA and CodY being important contributors to the altered growth in a fakA mutant. Indeed, it was found that directing amino acids from the urea cycle into the TCA cycle via glutamate dehydrogenase was an essential component of S. aureus growth after glucose depletion. Together, these data identify a previously unidentified role of FakA in the global physiology of S. aureus, linking external fatty acid utilization and central metabolism.IMPORTANCE The fatty acid kinase, FakA, of Staphylococcus aureus plays several important roles in the cell. FakA is important for the activation of the SaeRS two-component system and secreted virulence factors like α-hemolysin. However, the contribution of FakA to cellular metabolism has not been explored. Here, we highlight the metabolic consequence of removal of FakA from the cell. The absence of FakA leads to altered acetate metabolism and altered redox balance, as well as a change in intracellular amino acids. Additionally, the use of environmental amino acid sources is affected by FakA. Together, these results demonstrate for the first time that FakA provides a link between the pathways for exogenous fatty acid use, virulence factor regulation, and other metabolic processes.
| S-EPMC6148474 | biostudies-literature
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.
| S-EPMC3624546 | biostudies-literature
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.
2008-08-25 | GSE12210 | GEO
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.
| S-EPMC2965947 | biostudies-literature
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.
| S-EPMC6343930 | biostudies-literature
Project description:ObjectivesFusidic acid interferes with the release of elongation factor G (EF-G) after the translocation step of protein synthesis. The objective of this study was to characterize the fusidic acid stimulon of a fusidic acid-susceptible strain of Staphylococcus aureus (SH1000).MethodsS. aureus microarrays and real-time PCR determined transcriptome alterations occurring in SH1000 grown with fusidic acid. The Staphylococcus aureus microarray meta-database (SAMMD) compared and contrasted the SH1000 fusidic stimulon with 89 other S. aureus transcriptional datasets. Fusidic acid gradient analyses with mutant-parent strain pairs were used to identify genes required for intrinsic fusidic acid susceptibility identified during transcriptional analysis.ResultsMany genes altered by fusidic acid challenge are associated with protein synthesis. SAMMD analysis determined that the fusidic acid stimulon has the greatest overlap with the S. aureus cold shock and stringent responses. Six out of nine peptidoglycan hydrolase genes making up the two component YycFG regulon were also up-regulated by fusidic acid, as were a carboxylesterase gene (est) and two putative drug efflux pump genes (emr-qac1 and macA). Genes down-regulated by fusidic acid induction encoded a putative secreted acid phosphatase and a number of protease genes. Roles for the agr operon, the peptidoglycan hydrolase gene isaA and two proteases (htrA1 and htrA2) in the expression of fusidic acid susceptibility were revealed.ConclusionsThe SH1000 fusidic acid stimulon includes genes involved with two stress responses, YycFG-regulated cell wall metabolism, drug efflux, and protein synthesis and turnover.
| S-EPMC2583067 | biostudies-literature
Project description:Staphylococcus aureus can supplement its endogenous fatty acid synthesis pathway (FASII) with exogenous fatty acids it acquires from the environment through the fatty acid kinase (Fak) complex. While S. aureus has been thought to not degrade fatty acids, it does possess a potential fadXDEBA locus that contains all the genes necessary for -oxidation. Using mRNA analysis, we determined that the fadXDEBA operon can be found on one polycistronic mRNA. Moreover, we identified the fadX promoter and a putative binding site within this region that is consistent with negative regulation by the metabolism-responsive regulator, Carbon Catabolite Protein A (CcpA). Indeed, in the absence of glucose or CcpA, we saw the fadXDEBA operon was derepressed. S. aureus is annotated to lack the crotonase domain of FadB; however, new analysis indicates it is present. To test the functionality of the S. aureus FadB, we performed complementation assays with E. coli fad mutants using minimal media supplemented with single fatty acids. We were able to restore growth of E. coli fad mutants when providing safadBA genes on a plasmid and demonstrate that the SaFadB crotonase domain is required for complementation. Together, these data demonstrate the SaFadBA proteins are functional within a well characterized fatty acid degradation system and the fadXDEBA operon is under strong catabolite repression.
2025-06-05 | GSE299037 | GEO