Disease relevance of htrA

• Previous work has established that the E. coli htrA gene product is essential for bacterial survival at temperatures above 42 degrees [1].
• In addition, the presence of an intact htrA gene facilitated growth under heat stress but not under salt stress [2].
• A gene (htrA) coding for a stress-inducible HtrA-like protein from Lactobacillus helveticus CNRZ32 was cloned, sequenced, and characterized [2].
• A Yersinia pestis htrA orthologue was identified, cloned and sequenced, showing 86% and 87% similarity to Escherichia coli and Salmonella typhimurium HtrAs [3].
• Previous studies have shown that salmonella htrA mutants are excellent live vaccines [4].

High impact information on htrA

• Both the sigma32-dependent, dnaK and ibp, promoters, and the sigmaE-dependent, P3rpoH and htrA, promoters were rapidly but transiently induced when mid-exponential phase cells were treated with 0.464 M sucrose [5].
• We have sequenced the htrA gene region and found an open reading frame (ORF) coding for a protein of 491 amino acids with a calculated molecular weight of 51,163 daltons [1].
• However, the htrA mutant efficiently colonized the livers and spleens of mice infected i.v., but the rpoE mutant did not [4].
• Two known members of the CssRS regulon are the htrA and htrB genes, encoding potential extracytoplasmic chaperone proteases for protein quality control [6].
• Enhanced htrA mRNA expression was also seen in CNRZ32 cells after exposure to puromycin, ethanol, or heat [2].

Chemical compound and disease context of htrA

• HumHtrA2 or Omi is a recently described member of a novel family of mammalian serine proteases homologous to the Escherichia coli htrA gene product [7].

Biological context of htrA

• An isogenic Y. pestis htrA mutant was constructed using a reverse genetics approach [3].
• Two extragenic suppressors which allow temperature-sensitive htrA mutant Escherichia coli bacteria to grow at 42 degrees C and simultaneously acquire a cold-sensitive phenotype at 30 degrees C were isolated [8].

Anatomical context of htrA

• Inhibition of the growth of the htrA mutant by iron could be alleviated more efficiently by a nitroxide antioxidant that localizes in the membranes (A-TEMPO) than by a derivative (40H-TEMPO) that acts mainly in the soluble fraction of the cell [9].

Associations of htrA with chemical compounds

• Inhibition of the growth of the htrA mutant was more pronounced following treatment with cumene hydroperoxide, which partitions into membranes, than with t-butyl hydroperoxide, which forms radical mainly in the cytosol [9].
• We compared the influence of various oxidizing agents on htrA mutant cells with their effects on wild-type bacteria, and found that the htrA mutation did not increase sensitivity to hydrogen peroxide or paraquat but made the cell extremely sensitive to ferrous [Fe(II)] ions, which are known to enhance oxidation of proteins [9].

Other interactions of htrA

• By contrast, the mRNA levels of htrA and ppiB were decreased after induction of the alpha-glucosidase overexpression [10].

Analytical, diagnostic and therapeutic context of htrA

• For some organisms, htrA mutants are attenuated in the animal model and can be used as live vaccines [3].

References