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Role of streptococcal T antigens in superficial skin infection.

ABSTRACT: FCT region genes of Streptococcus pyogenes encode surface proteins that include fibronectin- and collagen-binding proteins and the serological markers known as T antigens, some of which give rise to pilus-like appendages. It remains to be established whether FCT region surface proteins contribute to virulence by in vivo models of infection. In this study, a highly sensitive and ecologically relevant humanized mouse model was used to measure superficial skin infection. Three genes encoding FCT region surface proteins essential for T-serotype specificity were inactivated. Both the Deltacpa and DeltaprtF2 mutants were highly attenuated for virulence when topically applied to the skin following exponential growth but were fully virulent when delivered in stationary phase. In contrast, the DeltafctA mutant was virulent at the skin, regardless of its initial growth state. Immunoblots of cell extracts revealed anti-FctA-reactive, ladder-like polymers characteristic of streptococcal pili. In addition, FctA formed a heteropolymer with the putative collagen-binding protein Cpa. The DeltafctA mutant showed a loss in anti-Cpa-reactive polymers, whereas anti-FctA-reactive polymers were reduced in the Deltacpa mutant. The findings suggest that both FctA and Cpa are required for pilus formation, but importantly, an intact pilus is not essential for Cpa-mediated virulence. Although it is an integral part of the T-antigen complex, the fibronectin-binding protein PrtF2 is not covalently linked to the FctA- and Cpa-containing heteropolymer derived from cell extracts. The data provide direct evidence that streptococcal T antigens function as virulence factors in vivo, but they also reveal that a pilus-like structure is not essential for the most common form of streptococcal skin disease.

SUBMITTER: Lizano S

PROVIDER: S-EPMC1797348 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature

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Role of streptococcal T antigens in superficial skin infection.

Lizano Sergio S Luo Feng F Bessen Debra E DE

Journal of bacteriology 20060929 4

FCT region genes of Streptococcus pyogenes encode surface proteins that include fibronectin- and collagen-binding proteins and the serological markers known as T antigens, some of which give rise to pilus-like appendages. It remains to be established whether FCT region surface proteins contribute to virulence by in vivo models of infection. In this study, a highly sensitive and ecologically relevant humanized mouse model was used to measure superficial skin infection. Three genes encoding FCT re ...[more]

PMID: 17012387

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Project description:BackgroundStreptoccocal A (Strep A, GAS) infections in Australia are responsible for significant morbidity and mortality through both invasive (iGAS) and post-streptococcal (postGAS) diseases as well as preceding superficial (sGAS) skin and throat infection. The burden of iGAS and postGAS are addressed in some jurisdictions by mandatory notification systems; in contrast, the burden of preceding sGAS has no reporting structure, and is less well defined. This review provides valuable, contemporaneous evidence on the epidemiology of sGAS presentations in Australia, informing preventative health projects such as a Streptococcal A vaccine and standardisation of primary care notification.Methods and findingsMEDLINE, Scopus, EMBASE, Web of Science, Global Health, Cochrane, CINAHL databases and the grey literature were searched for studies from an Australian setting relating to the epidemiology of sGAS infections between 1970 and 2020 inclusive. Extracted data were pooled for relevant population and subgroup analysis. From 5157 titles in the databases combined with 186 grey literature reports and following removal of duplicates, 4889 articles underwent preliminary title screening. The abstract of 519 articles were reviewed with 162 articles identified for full text review, and 38 articles identified for inclusion. The majority of data was collected for impetigo in Aboriginal and Torres Strait Islander populations, remote communities, and in the Northern Territory, Australia. A paucity of data was noted for Aboriginal and Torres Strait Islander people living in urban centres or with pharyngitis. Prevalence estimates have not significantly changed over time. Community estimates of impetigo point prevalence ranged from 5.5-66.1%, with a pooled prevalence of 27.9% [95% CI: 20.0-36.5%]. All studies excepting one included >80% Aboriginal and Torres Strait Islander people and all excepting two were in remote or very remote settings. Observed prevalence of impetigo as diagnosed in healthcare encounters was lower, with a pooled estimate of 10.6% [95% CI: 3.1-21.8%], and a range of 0.1-50.0%. Community prevalence estimates for pharyngitis ranged from 0.2-39.4%, with a pooled estimate of 12.5% [95% CI: 3.5-25.9%], higher than the prevalence of pharyngitis in healthcare encounters; ranging from 1.0-5.0%, and a pooled estimate of 2.0% [95% CI: 1.3-2.8%]. The review was limited by heterogeneity in study design and lack of comparator studies for some populations.ConclusionsSuperficial Streptococcal A infections contribute to an inequitable burden of disease in Australia and persists despite public health interventions. The burden in community studies is generally higher than in health-services settings, suggesting under-recognition, possible normalisation and missed opportunities for treatment to prevent postGAS. The available, reported epidemiology is heterogeneous. Standardised nation-wide notification for sGAS disease surveillance must be considered in combination with the development of a Communicable Diseases Network of Australia (CDNA) Series of National Guideline (SoNG), to accurately define and address disease burden across populations in Australia.Trial registrationThis review is registered with PROSPERO. Registration number: CRD42019140440.

Dataset Information

Role of streptococcal T antigens in superficial skin infection.

Publications

Role of streptococcal T antigens in superficial skin infection.

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