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PerR confers phagoc...
PerR confers phagocytic killing resistance and allows pharyngeal colonization by group A Streptococcus
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- Gryllos, Ioannis (författare)
- Harvard University
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- Grifantini, Renata (författare)
- Novartis Immunobiological Research Institute
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- Colaprico, Annalisa (författare)
- Novartis Immunobiological Research Institute
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- Cary, Max E (författare)
- University of Oklahoma
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- Hakansson, Anders (författare)
- Lund University,Lunds universitet,Experimentell infektionsmedicin, Malmö,Forskargrupper vid Lunds universitet,Experimental Infection Medicine, Malmö,Lund University Research Groups,Brigham and Women's Hospital / Harvard Medical School
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- Carey, David W (författare)
- University of Oklahoma
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- Suarez-Chavez, Maria (författare)
- University of Oklahoma
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- Kalish, Leslie A (författare)
- Harvard University
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- Mitchell, Paul D (författare)
- Harvard University
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- White, Gary L (författare)
- University of Oklahoma
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- Wessels, Michael R (författare)
- Harvard University
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(creator_code:org_t)
- 2008-09-05
- 2008
- Engelska.
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 4:9, s. 1000145-1000145
- Relaterad länk:
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http://dx.doi.org/10...
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https://journals.plo...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The peroxide response transcriptional regulator, PerR, is thought to contribute to virulence of group A Streptococcus (GAS); however, the specific mechanism through which it enhances adaptation for survival in the human host remains unknown. Here, we identify a critical role of PerR-regulated gene expression in GAS phagocytosis resistance and in virulence during pharyngeal infection. Deletion of perR in M-type 3 strain 003Sm was associated with reduced resistance to phagocytic killing in human blood and by murine macrophages in vitro. The increased phagocytic killing of the perR mutant was abrogated in the presence of the general oxidative burst inhibitor diphenyleneiodonium chloride (DPI), a result that suggests PerR-dependent gene expression counteracts the phagocyte oxidative burst. Moreover, an isogenic perR mutant was severely attenuated in a baboon model of GAS pharyngitis. In competitive infection experiments, the perR mutant was cleared from two animals at 24 h and from four of five animals by day 14, in sharp contrast to wild-type bacteria that persisted in the same five animals for 28 to 42 d. GAS genomic microarrays were used to compare wild-type and perR mutant transcriptomes in order to characterize the PerR regulon of GAS. These studies identified 42 PerR-dependent loci, the majority of which had not been previously recognized. Surprisingly, a large proportion of these loci are involved in sugar utilization and transport, in addition to oxidative stress adaptive responses and virulence. This finding suggests a novel role for PerR in mediating sugar uptake and utilization that, together with phagocytic killing resistance, may contribute to GAS fitness in the infected host. We conclude that PerR controls expression of a diverse regulon that enhances GAS resistance to phagocytic killing and allows adaptation for survival in the pharynx.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- Bacterial Proteins
- Carbohydrate Metabolism
- Gene Expression Profiling
- Humans
- Microbial Viability
- Oxidative Stress
- Pharynx
- Repressor Proteins
- Streptococcus pyogenes
- Transcription Factors
- Virulence
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Gryllos, Ioannis
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Grifantini, Rena ...
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Colaprico, Annal ...
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Cary, Max E
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Hakansson, Ander ...
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Carey, David W
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visa fler...
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Suarez-Chavez, M ...
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Kalish, Leslie A
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Mitchell, Paul D
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White, Gary L
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Wessels, Michael ...
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Infektionsmedici ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Cell och molekyl ...
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PLoS Pathogens
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Lunds universitet