An insert in the covS gene distinguishes a pharyngeal and a blood isolate of Streptococcus pyogenes found in the same individual

Garcia, Alan F.; Abe, Lucienne; Erdem, Güliz; Cortez, Chari L.; Kurahara, David; Yamaga, Karen

doi:10.1099/mic.0.042614-0

Cited by 21 publications

(17 citation statements)

References 27 publications

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“…It is particularly known to negatively control the expression of several virulence genes, including the capsular synthetic genes, sagA encoding the streptolysin S and speB encoding the pyrogenic exotoxin B (Heath et al, 1999). Mutants in the covRS locus, regardless of whether they are constructed in vitro or whether they occur spontaneously in animal models during experimental infections, render bacteria more virulent and highly invasive (Engleberg et al, 2001;Garcia et al, 2010;Heath et al, 1999). In S. agalactiae, the inactivation of covRS increases the expression of surface adhesins, and thus adhesion of the bacteria to human vaginal, cervical and respiratory epithelial cells, as well as to constituents of the extracellular matrix (Park et al, 2012).…”

Section: Mobile Genetic Element Of the Isas1 Familymentioning

confidence: 99%

Physiological impact of transposable elements encoding DDE transposases in the environmental adaptation of Streptococcus agalactiae

Fléchard

Gilot

2014

Microbiology

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We have referenced and described Streptococcus agalactiae transposable elements encoding DDE transposases. These elements belonged to nine families of insertion sequences (ISs) and to a family of conjugative transposons (TnGBSs). An overview of the physiological impact of the insertion of all these elements is provided. DDE-transposable elements affect S. agalactiae in a number of aspects of its capability to adapt to various environments and modulate the expression of several virulence genes, the scpB-lmB genomic region and the genes involved in capsule expression and haemolysin transport being the targets of several different mobile elements. The referenced mobile elements modify S. agalactiae behaviour by transferring new gene(s) to its genome, by modifying the expression of neighbouring genes at the integration site or by promoting genomic rearrangements. Transposition of some of these elements occurs in vivo, suggesting that by dynamically regulating some adaptation and/or virulence genes, they improve the ability of S. agalactiae to reach different niches within its host and ensure the 'success' of the infectious process.

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Section: Mobile Genetic Element Of the Isas1 Familymentioning

confidence: 99%

Physiological impact of transposable elements encoding DDE transposases in the environmental adaptation of Streptococcus agalactiae

Fléchard

Gilot

2014

Microbiology

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“…Inactivation of CovS derepressed these virulence determinants and enhanced GAS virulence in murine infection models. A variety of naturally inactivated covRS genotypes with spontaneous inactivating mutations of the CovR and CovS proteins have been identified in GAS isolates of different M serotypes from severe invasive infections, such as M1 (2), M3 (6), M53 (7), and M81 (8). The isolates were phenotypically highly virulent and displayed enhanced resistance to killing by the host immune system.…”

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confidence: 99%

CovRS-Regulated Transcriptome Analysis of a Hypervirulent M23 Strain of Group A Streptococcus pyogenes Provides New Insights into Virulence Determinants

et al. 2015

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The two-component control of virulence (Cov) regulator (R)-sensor (S) (CovRS) regulates the virulence of Streptococcus pyogenes (group A Streptococcus [GAS]). Inactivation of CovS during infection switches the pathogenicity of GAS to a more invasiveform by regulating transcription of diverse virulence genes via CovR. However, the manner in which CovRS controls virulence through expression of extended gene families has not been fully determined. In the current study, the CovS-regulated gene expression profiles of a hypervirulent emm23 GAS strain (M23ND/CovS negative [M23ND/CovS ؊ ]) and a noninvasive isogenic strain (M23ND/CovS ؉ ), under different growth conditions, were investigated. RNA sequencing identified altered expression of ϳ349 genes (18% of the chromosome). The data demonstrated that M23ND/CovS ؊ achieved hypervirulence by allowing enhanced expression of genes responsible for antiphagocytosis (e.g., hasABC), by abrogating expression of toxin genes (e.g., speB), and by compromising gene products with dispensable functions (e.g., sfb1). Among these genes, several (e.g., parE and parC) were not previously reported to be regulated by CovRS. Furthermore, the study revealed that CovS also modulated the expression of a broad spectrum of metabolic genes that maximized nutrient utilization and energy metabolism during growth and dissemination, where the bacteria encounter large variations in available nutrients, thus restructuring metabolism of GAS for adaption to diverse growth environments. From constructing a genome-scale metabolic model, we identified 16 nonredundant metabolic gene modules that constitute unique nutrient sources. These genes were proposed to be essential for pathogen growth and are likely associated with GAS virulence. The genome-wide prediction of genes associated with virulence identifies new candidate genes that potentially contribute to GAS virulence. IMPORTANCEThe CovRS system modulates transcription of ϳ18% of the genes in the Streptococcus pyogenes genome. Mutations that inactivate CovR or CovS enhance the virulence of this bacterium. We determined complete transcriptomes of a naturally CovS-inactivated invasive deep tissue isolate of an emm23 strain of S. pyogenes (M23ND) and its complemented avirulent variant (CovS ؉ ). We identified diverse virulence genes whose altered expression revealed a genetic switching of a nonvirulent form of M23ND to a highly virulent strain. Furthermore, we also systematically uncovered for the first time the comparative levels of expression of a broad spectrum of metabolic genes, which reflected different metabolic needs of the bacterium as it invaded deeper tissue of the human host. S treptococcus pyogenes is a group A Streptococcus (GAS) Grampositive (Gram ϩ ) pathogen that afflicts humans with diseases ranging from mild pharyngitis and impetigo to severe invasive necrotizing fasciitis and toxic shock syndrome. Postinfection sequelae can result in rheumatic fever and glomerulonephritis. The ϳ1.8-Mb genome of this species encodes a wide range ...

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“…Spontaneous mutations in the covRS genes arise in vivo during infection, resulting in capsule overproduction and hypervirulence of GAS (22)(23)(24). Interestingly, some GAS isolates with a functioning CovR/S system also produce a large capsule, raising the possibility that additional layers of regulation of capsule expression exist (25).…”

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confidence: 99%

Transcription of the Streptococcus pyogenes Hyaluronic Acid Capsule Biosynthesis Operon Is Regulated by Previously Unknown Upstream Elements

et al. 2014

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The important human pathogen Streptococcus pyogenes (group A Streptococcus [GAS]) produces a hyaluronic acid (HA) capsule that plays critical roles in immune evasion. Previous studies showed that the hasABC operon encoding the capsule biosynthesis enzymes is under the control of a single promoter, P1, which is negatively regulated by the two-component regulatory system CovR/S. In this work, we characterize the sequence upstream of P1 and identify a novel regulatory region controlling transcription of the capsule biosynthesis operon in the M1 serotype strain MGAS2221. This region consists of a promoter, P2, which initiates transcription of a novel small RNA, HasS, an intrinsic transcriptional terminator that inefficiently terminates HasS, permitting read-through transcription of hasABC, and a putative promoter which lies upstream of P2. Electrophoretic mobility shift assays, quantitative reverse transcription-PCR, and transcriptional reporter data identified CovR as a negative regulator of P2. We found that the P1 and P2 promoters are completely repressed by CovR, and capsule expression is regulated by the putative promoter upstream of P2. Deletion of hasS or of the terminator eliminates CovR-binding sequences, relieving repression and increasing read-through, hasA transcription, and capsule production. Sequence analysis of 44 GAS genomes revealed a high level of polymorphism in the HasS sequence region. Most of the HasS variations were located in the terminator sequences, suggesting that this region is under strong selective pressure. We discovered that the terminator deletion mutant is highly resistant to neutrophil-mediated killing and is significantly more virulent in a mouse model of GAS invasive disease than the wild-type strain. Together, these results are consistent with the naturally occurring mutations in this region modulating GAS virulence.

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An insert in the covS gene distinguishes a pharyngeal and a blood isolate of Streptococcus pyogenes found in the same individual

Cited by 21 publications

References 27 publications

Physiological impact of transposable elements encoding DDE transposases in the environmental adaptation of Streptococcus agalactiae

Physiological impact of transposable elements encoding DDE transposases in the environmental adaptation of Streptococcus agalactiae

CovRS-Regulated Transcriptome Analysis of a Hypervirulent M23 Strain of Group A Streptococcus pyogenes Provides New Insights into Virulence Determinants

Transcription of the Streptococcus pyogenes Hyaluronic Acid Capsule Biosynthesis Operon Is Regulated by Previously Unknown Upstream Elements

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