Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Staphylococcus aureus cell surface protein clumping factor A (ClfA) and the enzyme sortase A (SrtA), which attach surface proteins to the cell wall, have both been shown to be virulence factors in models of septic arthritis and sepsis. The mRNA levels of clfA, srtA and the putative housekeeping gene gyrase B (gyrB) in S. aureus were determined using real-time PCR during the course of sepsis/septic arthritis. Expression was measured in joints, being a target of localized infection, and in kidneys, representing a systemic compartment. In infected kidneys, the mRNA levels of clfA, srtA and gyrB were all decreasing over time, from day 3 of infection to day 14. The transcript numbers of clfA and srtA decreased faster in septic mice than in mice with a non-septic disease. The mRNA levels of clfA and gyrB in joints, though, were increasing during the course of infection. These differences suggest that the specific tissue environment is decisive for the differentiation of staphylococci. Also, there was a negative relationship between bacterial load in a tissue and the numbers of clfA, srtA and gyrB transcripts per colony-forming unit. Possibly enters the majority of bacteria a metabolically dormant steady state at high bacterial loads.
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PMID:In vivo sortase A and clumping factor A mRNA expression during Staphylococcus aureus infection. 1789 45

Pili are putative virulence factors and promising vaccine candidates in Streptococcus agalactiae (group B Streptococcus [GBS]) infection, a leading cause of neonatal sepsis and meningitis. The genes necessary for pilus synthesis and assembly are clustered in pilus islands (PI). Each gene encodes three structural subunits (a backbone and two ancillary proteins) bearing a C-terminal LPXTG motif and two subfamily C sortases (SrtC) involved in covalent polymerization of the subunits. GBS strains also possess the conserved "housekeeping" sortase A (SrtA), but its role in pilus assembly is unclear. To address this issue, pilus expression and cell wall anchoring were analyzed in srtA deletion mutants. Loss of SrtA did not affect pilus polymerization. However, pilus expression on the cell surface was reduced, and pili accumulated in the culture supernatant. Furthermore, cell-associated pili could be readily released by detergent treatment, indicating that SrtA is involved in covalent anchoring of pili to the cell wall. When each of the genes comprising PI-2a was systematically deleted, only the absence of ancillary subunit GBS150 or the SrtC required for incorporation of GBS150 into pili mimicked the srtA mutant phenotype. Thus, from these data a model for GBS pilus assembly can be proposed in which PI sortases are responsible for polymerization of the pilus structure, while SrtA is required to covalently attach it to the cell wall, utilizing ancillary pilus subunit GBS150 as the anchor protein.
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PMID:Sortase A utilizes an ancillary protein anchor for efficient cell wall anchoring of pili in Streptococcus agalactiae. 1854 57

Protein-based vaccines are considered to be the next-generation of pneumococcal vaccines. Here we evaluated the protection elicited by immunization with recombinant glutamyl tRNA synthetase (Gts), polyamine transport protein D (PotD) and sortase A (SrtA) antigens in preclinical mouse models. In mucosal immunization studies, intranasal immunization with either Gts, PotD or SrtA could significantly reduce pneumococcal nasopharyngeal and lung colonization and significantly increase mice survival times following invasive pneumococcal challenge, and combinations of these antigens could enhance this protection. In systemic immunization studies, intraperitoneal immunization with multiple protein antigens also provided better protection against pneumococcal sepsis caused by different pneumococcal strains. Finally, passive immunization studies showed an additive effect by using multiple anti-sera when compared to single anti-sera. Therefore, a multicomponent protein-based pneumococcal vaccine composed of Gts, PotD or SrtA could confer protection against pneumococcal colonization as well as invasive infections in terms of efficacy of protection and serotype coverage.
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PMID:Protection against pneumococcal infection elicited by immunization with glutamyl tRNA synthetase, polyamine transport protein D and sortase A. 2246 66