Dataset Information

The Heme Transporter HtsABC of Group A Streptococcus Contributes to Virulence and Innate Immune Evasion in Murine Skin Infections.

ABSTRACT: Group A Streptococcus (GAS) requires iron for growth, and heme is an important source of iron for GAS. Streptococcus heme transporter A (HtsA) is the lipoprotein component of the GAS heme-specific ABC transporter (HtsABC). The objective of this study is to examine the contribution of HtsABC to virulence and host interaction of hypervirulent M1T1 GAS using an isogenic htsA deletion mutant (?htsA). The htsA deletion exhibited a significantly increased survival rate, reduced skin lesion size, and reduced systemic GAS dissemination in comparison to the wild type strain. The htsA deletion also decreased the GAS adhesion rate to Hep-2 cells, the survival in human blood and rat neutrophils, and increased the production of cytokine IL-1?, IL-6, and TNF-? levels in air pouch exudate of a mouse model of subcutaneous infection. Complementation of ?htsA restored the wild type phenotype. These findings support that the htsA gene is required for GAS virulence and that the htsA deletion augments host innate immune responses.

SUBMITTER: Song Y

PROVIDER: S-EPMC5981463 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The Heme Transporter HtsABC of Group A Streptococcus Contributes to Virulence and Innate Immune Evasion in Murine Skin Infections.

Song Yingli Y Zhang Xiaolan X Cai Minghui M Lv Chunmei C Zhao Yuan Y Wei Deqin D Zhu Hui H

Frontiers in microbiology 20180525

Group A Streptococcus (GAS) requires iron for growth, and heme is an important source of iron for GAS. Streptococcus heme transporter A (HtsA) is the lipoprotein component of the GAS heme-specific ABC transporter (HtsABC). The objective of this study is to examine the contribution of HtsABC to virulence and host interaction of hypervirulent M1T1 GAS using an isogenic htsA deletion mutant (ΔhtsA). The htsA deletion exhibited a significantly increased survival rate, red ...[more]

PMID: 29887858

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Project description:Streptococcus agalactiae, a leading cause of sepsis and meningitis in neonates, utilizes multiple virulence factors to survive and thrive within the human host during an infection. Unique among the pathogenic streptococci, S. agalactiae uses a bifunctional enzyme encoded by a single gene (gshAB) to synthesize glutathione (GSH), a major antioxidant in most aerobic organisms. Since S. agalactiae can also import GSH, similar to all other pathogenic streptococcal species, the contribution of GSH synthesis to the pathogenesis of S. agalactiae disease is not known. In the present study, gshAB deletion mutants were generated in strains representing three of the most prevalent clinical serotypes of S. agalactiae and were compared against isogenic wild-type and gshAB knock-in strains. When cultured in vitro in a chemically defined medium under nonstress conditions, each mutant and its corresponding wild type had comparable growth rates, generation times, and growth yields. However, gshAB deletion mutants were found to be more sensitive than wild-type or gshAB knock-in strains to killing and growth inhibition by several different reactive oxygen species. Furthermore, deletion of gshAB in S. agalactiae strain COH1 significantly attenuated virulence compared to the wild-type or gshAB knock-in strains in a mouse model of sepsis. Taken together, these data establish that GSH is a virulence factor important for resistance to oxidative stress and that de novo GSH synthesis plays a crucial role in S. agalactiae pathogenesis and further suggest that the inhibition of GSH synthesis may provide an opportunity for the development of novel therapies targeting S. agalactiae disease.IMPORTANCE Approximately 10 to 30% of women are naturally and asymptomatically colonized by Streptococcus agalactiae However, transmission of S. agalactiae from mother to newborn during vaginal birth is a leading cause of neonatal meningitis. Although colonized mothers who are at risk for transmission to the newborn are treated with antibiotics prior to delivery, S. agalactiae is becoming increasingly resistant to current antibiotic therapies, and new treatments are needed. This research reveals a critical stress resistance pathway, glutathione synthesis, that is utilized by S. agalactiae and contributes to its pathogenesis. Understanding the role of this unique bifunctional glutathione synthesis enzyme in S. agalactiae during sepsis may help elucidate why S. agalactiae produces such an abundance of glutathione compared to other bacteria.

Dataset Information

The Heme Transporter HtsABC of Group A Streptococcus Contributes to Virulence and Innate Immune Evasion in Murine Skin Infections.

Publications

The Heme Transporter HtsABC of Group A <i>Streptococcus</i> Contributes to Virulence and Innate Immune Evasion in Murine Skin Infections.

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