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

2019 ◽  
Author(s):  
Stephanie Marroquin ◽  
Brittney Gimza ◽  
Brooke Tomlinson ◽  
Michelle Stein ◽  
Andrew Frey ◽  
...  
Keyword(s):  
Virulence Gene ◽  
Transcriptional Analysis ◽  
Virulence Determinants ◽  
Drastic Reduction ◽  
Virulence Gene Expression ◽  
Function Mechanism ◽  
Family Protein ◽  
Metalloprotease Activity ◽  
Direct Regulator

AbstractNumerous factors have to date been identified as playing a role in the regulation of Agr activity in S. aureus, including transcription factors, antisense RNAs, and host elements. Herein we investigate 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 datasets for both mroQ and agr mutants reveal 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 is not wielded at the level of AgrD processing. Virulence assessment demonstrated that mroQ and agr mutants both 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.

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.

scholarly journals RegA, an AraC-Like Protein, Is a Global Transcriptional Regulator That Controls Virulence Gene Expression in Citrobacter rodentium

2008 ◽  
Vol 76 (11) ◽  
pp. 5247-5256 ◽  
Author(s):  
Emily Hart ◽  
Ji Yang ◽  
Marija Tauschek ◽  
Michelle Kelly ◽  
Matthew J. Wakefield ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Virulence Gene ◽  
Virulence Determinants ◽  
Intestinal Colonization ◽  
Citrobacter Rodentium ◽  
Promoter Regions ◽  
Reading Frame ◽  
Virulence Gene Expression ◽  
Genes Encoding ◽  
Colonization Factors

ABSTRACT Citrobacter rodentium is an attaching and effacing pathogen which causes transmissible colonic hyperplasia in mice. Infection with C. rodentium serves as a model for infection of humans with enteropathogenic and enterohemorrhagic Escherichia coli. To identify novel colonization factors of C. rodentium, we screened a signature-tagged mutant library of C. rodentium in mice. One noncolonizing mutant had a single transposon insertion in an open reading frame (ORF) which we designated regA because of its homology to genes encoding members of the AraC family of transcriptional regulators. Deletion of regA in C. rodentium resulted in markedly reduced colonization of the mouse intestine. Examination of lacZ transcriptional fusions using promoter regions of known and putative virulence-associated genes of C. rodentium revealed that RegA strongly stimulated transcription of two newly identified genes located close to regA, which we designated adcA and kfcC. The cloned adcA gene conferred autoaggregation and adherence to mammalian cells to E. coli strain DH5α, and a kfc mutation led to a reduction in the duration of intestinal colonization, but the kfc mutant was far less attenuated than the regA mutant. These results indicated that other genes of C. rodentium whose expression required activation by RegA were required for colonization. Microarray analysis revealed a number of RegA-regulated ORFs encoding proteins homologous to known colonization factors. Transcription of these putative virulence determinants was activated by RegA only in the presence of sodium bicarbonate. Taken together, these results show that RegA is a global regulator of virulence in C. rodentium which activates factors that are required for intestinal colonization.

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 The Cpx System Regulates Virulence Gene Expression in Vibrio cholerae

2015 ◽  
Vol 83 (6) ◽  
pp. 2396-2408 ◽  
Author(s):  
Nicole Acosta ◽  
Stefan Pukatzki ◽  
Tracy L. Raivio
Keyword(s):  
Vibrio Cholerae ◽  
Response Regulator ◽  
Bacterial Species ◽  
Virulence Gene ◽  
Receptor Protein ◽  
Virulence Determinants ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Envelope Stress ◽  
El Tor

Bacteria possess signal transduction pathways capable of sensing and responding to a wide variety of signals. The Cpx envelope stress response, composed of the sensor histidine kinase CpxA and the response regulator CpxR, senses and mediates adaptation to insults to the bacterial envelope. The Cpx response has been implicated in the regulation of a number of envelope-localized virulence determinants across bacterial species. Here, we show that activation of the Cpx pathway inVibrio choleraeEl Tor strain C6706 leads to a decrease in expression of the major virulence factors in this organism, cholera toxin (CT) and the toxin-coregulated pilus (TCP). Our results indicate that this occurs through the repression of production of the ToxT regulator and an additional upstream transcription factor, TcpP. The effect of the Cpx response on CT and TCP expression is mostly abrogated in a cyclic AMP receptor protein (CRP) mutant, although expression of thecrpgene is unaltered. Since TcpP production is controlled by CRP, our data suggest a model whereby the Cpx response affects CRP function, which leads to diminished TcpP, ToxT, CT, and TCP production.

scholarly journals The Emergence of Invasive Streptococcus pneumoniae Serotype 24F in Lebanon: Complete Genome Sequencing Reveals High Virulence and Antimicrobial Resistance Characteristics

2021 ◽  
Vol 12 ◽  
Author(s):  
Lina Reslan ◽  
Marc Finianos ◽  
Ibrahim Bitar ◽  
Mohamad Bahij Moumneh ◽  
George F. Araj ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Antimicrobial Resistance ◽  
Tetracycline Resistance ◽  
Virulence Gene ◽  
Surveillance Program ◽  
Virulence Determinants ◽  
Tetracycline Resistance Genes ◽  
Long Reads ◽  
Genomic Characterization

BackgroundInvasive pneumococcal disease (IPD) remains a global health problem. IPD incidence has significantly decreased by the use of pneumococcal conjugate vaccines (PCV). Nevertheless, non-PCV serotypes remain a matter of concern. Eight Streptococcus pneumoniae serotype 24F isolates, belonging to a non-PCV serotype, were detected through the Lebanese Inter-Hospital Pneumococcal Surveillance Program. The aim of the study is to characterize phenotypic and genomic features of the 24F isolates in Lebanon.MethodsWGS using long reads sequencing (PacBio) was performed to produce complete circular genomes and to determine clonality, antimicrobial resistance and virulence determinants.ResultsThe sequencing results yielded eight closed circular genomes. Three multilocus sequence typing (MLST) types were identified (ST11618, ST14184, ST15253). Both MLST and WGS analyses revealed that these isolates from Lebanon were genetically homogenous belonging to clonal complex CC230 and clustered closely with isolates originating from Canada, United States of America, United Kingdom and Iceland. Their penicillin binding protein profiles correlated with both β-lactam susceptibility patterns and MLST types. Moreover, the isolates harbored the macrolide and tetracycline resistance genes and showed a similar virulence gene profile. To our knowledge, this study represents the first report of complete phenotypic and genomic characterization of the emerging Streptococcus pneumoniae, serotype 24F, in the Middle East and North Africa region.

scholarly journals NAD+ pool depletion as a signal for the Rex regulon involved in Streptococcus agalactiae virulence

2021 ◽  
Vol 17 (8) ◽  
pp. e1009791
Author(s):  
Thierry Franza ◽  
Annika Rogstam ◽  
Saravanamuthu Thiyagarajan ◽  
Matthew J. Sullivan ◽  
Aurelie Derré-Bobillot ◽  
...  
Keyword(s):  
Gene Expression ◽  
Streptococcus Agalactiae ◽  
Group B Streptococcus ◽  
Virulence Gene ◽  
Opportunistic Pathogen ◽  
Virulence Gene Expression ◽  
Gram Positive Bacteria ◽  
Virulence Factor Gene ◽  
Group B

In many Gram-positive bacteria, the redox-sensing transcriptional repressor Rex controls central carbon and energy metabolism by sensing the intra cellular balance between the reduced and oxidized forms of nicotinamide adenine dinucleotide; the NADH/NAD+ ratio. Here, we report high-resolution crystal structures and characterization of a Rex ortholog (Gbs1167) in the opportunistic pathogen, Streptococcus agalactiae, also known as group B streptococcus (GBS). We present structures of Rex bound to NAD+ and to a DNA operator which are the first structures of a Rex-family member from a pathogenic bacterium. The structures reveal the molecular basis of DNA binding and the conformation alterations between the free NAD+ complex and DNA-bound form of Rex. Transcriptomic analysis revealed that GBS Rex controls not only central metabolism, but also expression of the monocistronic rex gene as well as virulence gene expression. Rex enhances GBS virulence after disseminated infection in mice. Mechanistically, NAD+ stabilizes Rex as a repressor in the absence of NADH. However, GBS Rex is unique compared to Rex regulators previously characterized because of its sensing mechanism: we show that it primarily responds to NAD+ levels (or growth rate) rather than to the NADH/NAD+ ratio. These results indicate that Rex plays a key role in GBS pathogenicity by modulating virulence factor gene expression and carbon metabolism to harvest nutrients from the host.

scholarly journals Characterization of BPSS1521 (bprD), a Regulator of Burkholderia pseudomallei Virulence Gene Expression in the Mouse Model

PLoS ONE ◽  
2014 ◽  
Vol 9 (8) ◽  
pp. e104313 ◽  
Author(s):  
Sunisa Chirakul ◽  
Thanatchaporn Bartpho ◽  
Thidathip Wongsurawat ◽  
Suwimol Taweechaisupapong ◽  
Nitsara Karoonutaisiri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Burkholderia Pseudomallei ◽  
Virulence Gene ◽  
Virulence Gene Expression

scholarly journals Transcriptomic Analysis of Vibrio parahaemolyticus Reveals Different Virulence Gene Expression in Response to Benzyl Isothiocyanate

Molecules ◽  
2019 ◽  
Vol 24 (4) ◽  
pp. 761 ◽  
Author(s):  
Jie Song ◽  
Hong-Man Hou ◽  
Hong-Yan Wu ◽  
Ke-Xin Li ◽  
Yan Wang ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Vibrio Parahaemolyticus ◽  
Molecular Mechanisms ◽  
Virulence Gene ◽  
Differentially Expressed ◽  
Transcriptional Analysis ◽  
Effective Control ◽  
Benzyl Isothiocyanate ◽  
Virulence Gene Expression ◽  
Sequencing Studies

Vibrio parahaemolyticus isolated from seafood is a pathogenic microorganism that leads to several acute diseases that are harmful to our health and is frequently transmitted by food. Therefore, there is an urgent need for the control and suppression of this pathogen. In this paper, transcriptional analysis was used to determine the effect of treatment with benzyl isothiocyanate (BITC) extracted from cruciferous vegetables on V. parahaemolyticus and to elucidate the molecular mechanisms underlying the response to BITC. Treatment with BITC resulted in 332 differentially expressed genes, among which 137 genes were downregulated, while 195 genes were upregulated. Moreover, six differentially expressed genes (DEGs) in RNA sequencing studies were further verified by quantitative real-time polymerase chain reaction (qRT-PCR). Genes found to regulate virulence encoded an l-threonine 3-dehydrogenase, a GGDEF family protein, the outer membrane protein OmpV, a flagellum-specific adenosine triphosphate synthase, TolQ protein and VirK protein. Hence, the results allow us to speculate that BITC may be an effective control strategy for inhibiting microorganisms growing in foods.

Characterization of a virG mutation that confers constitutive virulence gene expression in Agrobacterium

1993 ◽  
Vol 7 (4) ◽  
pp. 555-562 ◽  
Author(s):  
Shouguang Jin ◽  
Yan-nong Song ◽  
Shen Q. Pan ◽  
Eugene W. Nester
Keyword(s):  
Gene Expression ◽  
Virulence Gene ◽  
Virulence Gene Expression
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