scholarly journals Staphylococcus aureus CcpA Affects Virulence Determinant Production and Antibiotic Resistance

2006 ◽  
Vol 50 (4) ◽  
pp. 1183-1194 ◽  
Author(s):  
Kati Seidl ◽  
Martin Stucki ◽  
Martin Ruegg ◽  
Christiane Goerke ◽  
Christiane Wolz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Capsular Polysaccharide ◽  
Protein A ◽  
Virulence Gene ◽  
Exponential Growth Phase ◽  
Virulence Determinants ◽  
Resistance Level ◽  
Virulence Gene Expression ◽  
Oxacillin Resistance

ABSTRACT Carbon catabolite protein A (CcpA) is known to function as a major regulator of gene expression in different gram-positive organisms. Deletion of the ccpA homologue (saCOL1786) in Staphylococcus aureus was found to affect growth, glucose metabolization, and transcription of selected virulence determinants. In liquid culture, deletion of CcpA decreased the growth rate and yield; however, the effect was only transient during the exponential-growth phase as long as glucose was present in the medium. Depletion of glucose and production of lactate was delayed, while the level of excretion of acetate was less affected and was even higher in the mutant culture. On solid medium, in contrast, growth of the ΔccpA mutant resulted in smaller colonies containing a lower number of CFU per colony. Deletion of CcpA had an effect on the expression of important virulence factors of S. aureus by down-regulating RNAIII, the effector molecule of the agr locus, and altering the transcription patterns of hla, encoding α-hemolysin, and spa, encoding protein A. CcpA inactivation markedly reduced the oxacillin resistance levels in the highly methicillin-resistant S. aureus strain COLn and the teicoplanin resistance level in a glycopeptide-intermediate-resistant S. aureus strain. The presence of CcpA in the capsular polysaccharide serotype 5 (CP5)-producing strain Newman abolished capsule formation and decreased cap operon transcription in the presence of glucose. The staphylococcal CcpA thus not only is involved in the regulation of carbon metabolism but seems to function as a modulator of virulence gene expression as well.

scholarly journals Molecular Architecture of the Regulatory Locus sae of Staphylococcus aureus and Its Impact on Expression of Virulence Factors

2003 ◽  
Vol 185 (21) ◽  
pp. 6278-6286 ◽  
Author(s):  
Andrea Steinhuber ◽  
Christiane Goerke ◽  
Manfred G. Bayer ◽  
Gerd Döring ◽  
Christiane Wolz
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Capsular Polysaccharide ◽  
Virulence Gene ◽  
Open Reading Frames ◽  
Exponential Growth Phase ◽  
Molecular Architecture ◽  
Stem Loop ◽  
Transcriptional Initiation ◽  
Virulence Gene Expression

ABSTRACT We characterized the sae operon, a global regulator for virulence gene expression in Staphylococcus aureus. A Tn917 sae mutant was obtained by screening a Tn917 library of the agr mutant ISP479Mu for clones with altered hemolytic activity. Sequence analysis of the sae operon revealed two additional open reading frames (ORFs) (ORF3 and ORF4) upstream of the two-component regulatory genes saeR and saeS. Four overlapping sae-specific transcripts (T1 to T4) were detected by Northern blot analysis, and the transcriptional initiation points were mapped by primer extension analysis. The T1, T2, and T3 mRNAs are probably terminated at the same stem-loop sequence downstream of saeS. The T1 message (3.1 kb) initiates upstream of ORF4, T2 (2.4 kb) initiates upstream of ORF3, and T3 (2.0 kb) initiates in front of saeR. T4 (0.7 kb) represents a monocistronic mRNA encompassing ORF4 only. sae-specific transcripts were detectable in all of the 40 different clinical S. aureus isolates investigated. Transcript levels were at maximum during the post-exponential growth phase. The sae mutant showed a significantly reduced rate of invasion of human endothelial cells, consistent with diminished transcription and expression of fnbA. The expression of type 5 capsular polysaccharide is activated in the sae mutant of strain Newman, as shown by immunofluorescence and promoter-reporter fusion experiments. In summary, the sae operon constitutes a four-component regulator system which acts on virulence gene expression in S. aureus.

scholarly journals TcaR, a Putative MarR-Like Regulator of sarS Expression

2004 ◽  
Vol 186 (10) ◽  
pp. 2966-2972 ◽  
Author(s):  
Nadine McCallum ◽  
Markus Bischoff ◽  
Hideki Maki ◽  
Akihito Wada ◽  
Brigitte Berger-Bächi
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Regulatory Element ◽  
Protein A ◽  
Virulence Gene ◽  
Transcriptional Regulators ◽  
Northern Blots ◽  
Virulence Gene Expression ◽  
Low Levels

ABSTRACT TcaR, which shares sequence homology with MarR-like transcriptional regulators, has been identified as a novel Staphylococcus aureus regulator affecting the expression of the global regulatory element SarS (SarH1), as well as that of the cell surface-associated protein SasF (N315-SA2439). Microarray analysis, confirmatory Northern blots, and genetic complementation experiments showed that TcaR upregulates sarS and thus spa transcription. In addition, it attenuates whole-length transcription of sasF, thereby producing a truncated transcript lacking the 3′ terminus, which codes for the cell wall anchor motif. Hence, in strains containing an intact tcaR gene, TcaR is likely to decrease the amount of the surface-associated protein SasF and to increase that of the surface-associated protein A. The widely used laboratory strains derived from NCTC8325 were found to be natural, truncated mutants of tcaR, harboring an inactive TcaR and therefore expressing very low levels of sarS. The data presented here identified TcaR as a further activator of sarS, and a modulator of sasF expression that has to be taken into account in studies of virulence gene expression in S. aureus.

scholarly journals MsrR, a Putative Cell Envelope-Associated Element Involved in Staphylococcus aureus sarA Attenuation

2003 ◽  
Vol 47 (8) ◽  
pp. 2558-2564 ◽  
Author(s):  
Jutta Rossi ◽  
Markus Bischoff ◽  
Akihito Wada ◽  
Brigitte Berger-Bächi
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Regulatory Network ◽  
Cell Envelope ◽  
Protein A ◽  
Virulence Gene ◽  
Exponential Growth Phase ◽  
Alpha Toxin ◽  
Altered Expression ◽  
Virulence Gene Expression

ABSTRACT A novel membrane-associated protein, MsrR, was identified in Staphylococcus aureus which affects resistance to methicillin and teicoplanin, as well as the synthesis of virulence factors. MsrR belongs to the LytR-CpsA-Psr family of cell envelope-related transcriptional attenuators and was shown to be inducible by cell wall-active agents, such as β-lactams, glycopeptides, and lysostaphin. The expression of msrR peaked in the early exponential growth phase and decreased sharply thereafter. msrR mutants showed increased sarA transcription and an earlier and higher expression of RNAIII, resulting in altered expression of virulence factors such as alpha-toxin and protein A. These observations suggest that MsrR is a new component involved in sarA attenuation and the regulatory network controlling virulence gene expression in S. aureus.

scholarly journals Differential Expression and Roles of Staphylococcus aureus Virulence Determinants during Colonization and Disease

mBio ◽  
2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Amy Jenkins ◽  
Binh An Diep ◽  
Thuy T. Mai ◽  
Nhung H. Vo ◽  
Paul Warrener ◽  
...  
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Virulence Gene ◽  
Nasal Colonization ◽  
Virulence Determinants ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Invasive Pathogen ◽  
Knockout Mutants ◽  
Insight Into

ABSTRACTStaphylococcus aureusis a Gram-positive, commensal bacterium known to asymptomatically colonize the human skin, nares, and gastrointestinal tract. Colonized individuals are at increased risk for developing S. aureus infections, which range from mild skin and soft tissue infections to more severe diseases, such as endocarditis, bacteremia, sepsis, and osteomyelitis. Different virulence factors are required for S. aureus to infect different body sites. In this study, virulence gene expression was analyzed in two S. aureus isolates during nasal colonization, bacteremia and in the heart during sepsis. These models were chosen to represent the stepwise progression of S. aureus from an asymptomatic colonizer to an invasive pathogen. Expression of 23 putative S. aureus virulence determinants, representing protein and carbohydrate adhesins, secreted toxins, and proteins involved in metal cation acquisition and immune evasion were analyzed. Consistent upregulation ofsdrC,fnbA,fhuD,sstD, andhlawas observed in the shift between colonization and invasive pathogen, suggesting a prominent role for these genes in staphylococcal pathogenesis. Finally, gene expression data were correlated to the roles of the genes in pathogenesis by using knockout mutants in the animal models. These results provide insights into how S. aureus modifies virulence gene expression between commensal and invasive pathogens.IMPORTANCEMany bacteria, such asStaphylococcus aureus, asymptomatically colonize human skin and nasal passages but can also cause invasive diseases, such as bacteremia, pneumonia, sepsis, and osteomyelitis. The goal of this study was to analyze differences in the expression of selected S. aureus genes during a commensal lifestyle and as an invasive pathogen to gain insight into the commensal-to-pathogen transition and how a bacterial pathogen adapts to different environments within a host (e.g., from nasal colonization to invasive pathogen). The gene expression data were also used to select genes for which to construct knockout mutants to assess the role of several proteins in nasal colonization and lethal bacteremia. These results not only provide insight into the factors involved in S. aureus disease pathogenesis but also provide potential therapeutic targets.

scholarly journals Norlichexanthone Reduces Virulence Gene Expression and Biofilm Formation in Staphylococcus aureus

PLoS ONE ◽  
2016 ◽  
Vol 11 (12) ◽  
pp. e0168305 ◽  
Author(s):  
Mara Baldry ◽  
Anita Nielsen ◽  
Martin S. Bojer ◽  
Yu Zhao ◽  
Cathrine Friberg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Virulence Gene ◽  
Virulence Gene Expression

scholarly journals Nigribactin, a Novel Siderophore from Vibrio nigripulchritudo, Modulates Staphylococcus aureus Virulence Gene Expression

Marine Drugs ◽  
2012 ◽  
Vol 10 (12) ◽  
pp. 2584-2595 ◽  
Author(s):  
Anita Nielsen ◽  
Maria Mansson ◽  
Matthias Wietz ◽  
Anders Varming ◽  
Richard Phipps ◽  
...  
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Virulence Gene ◽  
Virulence Gene Expression

scholarly journals Novel Inhibitors of Staphylococcus aureus Virulence Gene Expression and Biofilm Formation

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e47255 ◽  
Author(s):  
Yibao Ma ◽  
Yuanxi Xu ◽  
Bryan D. Yestrepsky ◽  
Roderick J. Sorenson ◽  
Meng Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Virulence Gene ◽  
Virulence Gene Expression

scholarly journals mgr, a Novel Global Regulator in Staphylococcus aureus

2003 ◽  
Vol 185 (13) ◽  
pp. 3703-3710 ◽  
Author(s):  
Thanh T. Luong ◽  
Steven W. Newell ◽  
Chia Y. Lee
Keyword(s):  
Staphylococcus Aureus ◽  
Capsular Polysaccharide ◽  
Polyacrylamide Gel Electrophoresis ◽  
Protein A ◽  
Sodium Dodecyl ◽  
Binding Motif ◽  
Transcriptional Level ◽  
Virulence Determinants ◽  
Alpha Toxin ◽  
Extracellular Protein Production

ABSTRACT The virulence determinants of Staphylococcus aureus are coordinately controlled by several unlinked chromosomal loci. Here, we report the identification of CYL5614, derived from strain Becker, with a mutation that affects the expression of type 8 capsular polysaccharide (CP8), nuclease, alpha-toxin, coagulase, protease, and protein A. This novel locus, named mgr, was linked by transposon Tn917 and mapped by three-factorial transduction crosses. The region containing the mgr locus was cloned and sequenced. Deletion mutagenesis and genetic complementation showed that the locus consisted of one gene, mgrA. Interestingly, mgrA-null mutants exhibited a phenotype opposite to that of CYL5614. This was due to a T-to-C mutation upstream of mgrA that resulted in a four- to eightfold increase in mgrA transcription in strain CYL5614. Thus, these results indicate that mgrA is an activator of CP8 and nuclease but a repressor of alpha-toxin, coagulase, protease, and protein A. In addition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses showed that the mgr locus profoundly affected extracellular protein production, suggesting that the locus may regulate many other genes as well. The translated MgrA protein has a region of significant homology, which includes the helix-turn-helix DNA-binding motif, with the Escherichia coli MarR family of transcriptional regulators. Northern slot blot analyses suggested that mgr affected CP8, alpha-toxin, nuclease, and protein A at the transcriptional level.

scholarly journals MroQ Is a Novel Abi-Domain Protein That Influences Virulence Gene Expression in Staphylococcus aureus via Modulation of Agr Activity

2019 ◽  
Vol 87 (5) ◽  
Author(s):  
Stephanie Marroquin ◽  
Brittney Gimza ◽  
Brooke Tomlinson ◽  
Michelle Stein ◽  
Andrew Frey ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Gene ◽  
Transcriptional Analysis ◽  
Data Sets ◽  
Virulence Determinants ◽  
Sequencing Data ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Function Mechanism ◽  
Family Protein

ABSTRACT Numerous factors have, to date, been identified as playing a role in the regulation of Agr activity in Staphylococcus aureus, including transcription factors, antisense RNAs, and host elements. Herein we investigated the product of SAUSA300_1984 (termed MroQ), a transmembrane Abi-domain/M79 protease-family protein, as a novel effector of this system. Using a USA300 mroQ mutant, we observed a drastic reduction in proteolysis, hemolysis, and pigmentation that was fully complementable. This appears to result from diminished agr activity, as transcriptional analysis revealed significant decreases in expression of both RNAII and RNAIII in the mroQ mutant. Such effects appear to be direct, rather than indirect, as known agr effectors demonstrated limited alterations in their activity upon mroQ disruption. A comparison of RNA sequencing data sets for both mroQ and agr mutants revealed a profound overlap in their regulomes, with the majority of factors affected being known virulence determinants. Importantly, the preponderance of alterations in expression were more striking in the agr mutant, indicating that MroQ is necessary, but not sufficient, for Agr function. Mechanism profiling revealed that putative residues for metalloprotease activity within MroQ are required for its Agr-controlling effect; however, this was not wielded at the level of AgrD processing. Virulence assessment demonstrated that both mroQ and agr mutants exhibited increased formation of renal abscesses but decreased skin abscess formation alongside diminished dermonecrosis. Collectively, we present the characterization of a novel agr effector in S. aureus which would appear to be a direct regulator, potentially functioning via interaction with the AgrC histidine kinase.

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