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10.1128/IAI.00386-20

http://scihub22266oqcxt.onion/10.1128/IAI.00386-20
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32817331!7573446!32817331
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suck abstract from ncbi

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  • Single Amino Acid Replacements in RocA Disrupt Protein-Protein Interactions To Alter the Molecular Pathogenesis of Group A Streptococcus #MMPMID32817331
  • Bernard PE; Duarte A; Bogdanov M; Musser JM; Olsen RJ
  • Infect Immun 2020[Oct]; 88 (11): ä PMID32817331show ga
  • Group A Streptococcus (GAS) is a human-specific pathogen and major cause of disease worldwide. The molecular pathogenesis of GAS, like many pathogens, is dependent on the coordinated expression of genes encoding different virulence factors. The control of virulence regulator/sensor (CovRS) two-component system is a major virulence regulator of GAS that has been extensively studied. More recent investigations have also involved regulator of Cov (RocA), a regulatory accessory protein to CovRS. RocA interacts, in some manner, with CovRS; however, the precise molecular mechanism is unknown. Here, we demonstrate that RocA is a membrane protein containing seven transmembrane helices with an extracytoplasmically located N terminus and cytoplasmically located C terminus. For the first time, we demonstrate that RocA directly interacts with itself (RocA) and CovS, but not CovR, in intact cells. Single amino acid replacements along the entire length of RocA disrupt RocA-RocA and RocA-CovS interactions to significantly alter the GAS virulence phenotype as defined by secreted virulence factor activity in vitro and tissue destruction and mortality in vivo In summary, we show that single amino acid replacements in a regulatory accessory protein can affect protein-protein interactions to significantly alter the virulence of a major human pathogen.
  • |Amino Acid Sequence[MESH]
  • |Amino Acid Substitution[MESH]
  • |Animals[MESH]
  • |Bacterial Proteins/chemistry/*genetics/metabolism[MESH]
  • |Binding Sites[MESH]
  • |Cloning, Molecular[MESH]
  • |Escherichia coli/genetics/metabolism[MESH]
  • |Fasciitis, Necrotizing/metabolism/*microbiology/mortality/pathology[MESH]
  • |Female[MESH]
  • |Gene Expression[MESH]
  • |Gene Expression Regulation, Bacterial[MESH]
  • |Genetic Vectors/chemistry/metabolism[MESH]
  • |Histidine Kinase/chemistry/*genetics/metabolism[MESH]
  • |Humans[MESH]
  • |Mice[MESH]
  • |Mutation[MESH]
  • |Myositis/metabolism/*microbiology/mortality/pathology[MESH]
  • |Protein Binding[MESH]
  • |Protein Interaction Domains and Motifs[MESH]
  • |Protein Structure, Secondary[MESH]
  • |Repressor Proteins/chemistry/*genetics/metabolism[MESH]
  • |Streptococcal Infections/metabolism/*microbiology/mortality/pathology[MESH]
  • |Streptococcus pyogenes/*genetics/growth & development/metabolism/pathogenicity[MESH]
  • |Survival Analysis[MESH]
  • |Trans-Activators/chemistry/*genetics/metabolism[MESH]
  • |Virulence[MESH]


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  • suck abstract from ncbi

    ä 11.88 2020