Group A
            <i>Streptococcus</i>
            adaptation to diverse niches: lessons from transcriptomic studies

Schiavolin, Lionel; Deneubourg, Geoffrey; Steinmetz, Jenny; Smeesters, Pierre R.; Botteaux, Anne

doi:10.1080/1040841x.2023.2294905

Cited by 3 publications

References 191 publications

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Asparagine couples group AStreptococcalmetabolism to virulence

Sharma,

Anand,

Ravins

et al. 2024

Preprint

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Streptococcus(GAS) is a highly adapted and human-restricted pathogen causing a wide variety of infections, some life-threatening1. This ability is linked to the expression of many virulence factors, whose transcription is regulated by the two-component system, CovR/S2–5.Here, we show that genome transcription of GAS cultured in a chemically defined medium (CDM) is globally affected when supplemented with asparagine (Asn), including increased expression of many virulence genes. For the first time, we report that GAS solely depends on asparagine synthetase (AsnA) for Asn synthesis, on the ABC transporter (GlnPQ) to import Asn, and on the asparaginase (AsnB) to maintain a precisely balanced intracellular Asn concentration. Furthermore, we show that mutants defective in eitherasnA,glnP, orasnB express significantly lower levels of virulence factors in CDM and are severely attenuated in the sublethal murine model of human GAS soft-tissue infection.We further show that the synthesis and import of Asn in GAS are ATP-dependent and negatively regulated by intracellular Asn. Thus, Asn availability controls the intracellular ATP level. When ATP becomes limiting, CovR phosphorylation decreases. This augments GAS growth rate, virulence production, metabolism, andvice versawhen the ATP level increases. Furthermore, excess Asn accumulates inside GAS in AsnB mutant, destroying the balance between Asn and ATP. We discuss the high similarity between these mechanistic principles of the Asn-mediated control of GAS virulence and metabolism to the Asn-mediated control of tumor growth6, indicating evolutionary significance.

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Asparagine couples group AStreptococcalmetabolism to virulence

Sharma,

Anand,

Ravins

et al. 2024

Preprint

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The group A Streptococcus pathogenicity island RD2: virulence role and barriers to conjugative transfer

Roshika,

Baral,

Jain

et al. 2024

Infect Immun

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Serotype M28 isolates of the bacterial pathogen the group A Streptococcus (GAS; Streptococcus pyogenes ), but not isolates of other serotypes, have a nonrandom association with cases of puerperal sepsis, a life-threatening infection that can occur in women following childbirth. In prior studies, we established that RD2, a pathogenicity island present in all M28 GAS isolates but mostly absent from other serotypes, is a factor in the M28–puerperal sepsis association. Here, we identified a significant reduction in the RD2 conjugation frequency in inter-serotype conjugation assays relative to intra-serotype assays. As isolates of most GAS serotypes produce an antiphagocytic hyaluronic acid capsule, while M28 isolates do not, we tested whether the capsule served as a barrier to RD2 acquisition or maintenance. The data showed that capsule production had no impact on the RD2 conjugation frequency or on the ability of RD2 to enhance vaginal colonization by GAS, but did inhibit the ability of RD2 to enhance GAS adherence to vaginal epithelial cell lines. Further molecular explanations for the inter-serotype barrier to RD2 conjugative transfer were investigated, and a conserved, chromosomally encoded Type I restriction–modification system was identified as being key. We also identified that RD2 modifies the GAS transcriptome, including mRNAs encoding virulence factors with adherence and dissemination roles, following exposure to human plasma. Our data provide insights into factors that contribute to the restriction of the RD2 pathogenicity island to discrete subsets of the GAS population.

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Nosocomial Transmission of Necrotizing Fasciitis: A Molecular Characterization of Group A Streptococcal DNases in Clinical Virulence

Deneubourg,

Schiavolin,

Lakhloufi

et al. 2024

Microorganisms

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Streptococcus pyogenes, or Group A Streptococcus (GAS), is responsible for over 500,000 deaths per year. Approximately 15% of these deaths are caused by necrotizing soft-tissue infections. In 2008, we isolated an M5 GAS, named the LO1 strain, responsible for the nosocomial transmission of necrotizing fasciitis between a baby and a nurse in Belgium. To understand this unusual transmission route, the LO1 strain was sequenced. A comparison of the LO1 genome and transcriptome with the reference M5 Manfredo strain was conducted. We found that the major differences were the presence of an additional DNase and a Tn916-like transposon in the LO1 and other invasive M5 genomes. RNA-seq analysis showed that genes present on the transposon were barely expressed. In contrast, the DNases presented different expression profiles depending on the tested conditions. We generated knock-out mutants in the LO1 background and characterized their virulence phenotype. We also determined their nuclease activity on different substrates. We found that DNases are dispensable for biofilm formation and adhesion to both keratinocytes and pharyngeal cells. Three of these were found to be essential for blood survival; Spd4 and Sdn are implicated in phagocytosis resistance, and Spd1 is responsible for neutrophil extracellular trap (NET) degradation.

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Group A Streptococcus adaptation to diverse niches: lessons from transcriptomic studies

Cited by 3 publications

References 191 publications

Asparagine couples group AStreptococcalmetabolism to virulence

Asparagine couples group AStreptococcalmetabolism to virulence

The group A Streptococcus pathogenicity island RD2: virulence role and barriers to conjugative transfer

Nosocomial Transmission of Necrotizing Fasciitis: A Molecular Characterization of Group A Streptococcal DNases in Clinical Virulence

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