Role of Histone-Like Proteins H-NS and StpA in Expression of Virulence Determinants of Uropathogenic Escherichia coli

Abstract

The histone-like protein H-NS is a global regulator in Escherichia coli that has been intensively studied in nonpathogenic strains. However, no comprehensive study on the role of H-NS and its paralogue, StpA, in gene expression in pathogenic E. coli has been carried out so far. Here, we monitored the global effects of H-NS and StpA in a uropathogenic E. coli isolate by using DNA arrays. Expression profiling revealed that more than 500 genes were affected by an hns mutation, whereas no effect of StpA alone was observed. An hns stpA double mutant showed a distinct gene expression pattern that differed in large part from that of the hns single mutant. This suggests a direct interaction between the two paralogues and the existence of distinct regulons of H-NS and an H-NS/StpA heteromeric complex. hns mutation resulted in increased expression of alpha-hemolysin, fimbriae, and iron uptake systems as well as genes involved in stress adaptation. Furthermore, several other putative virulence genes were found to be part of the H-NS regulon. Although the lack of H-NS, either alone or in combination with StpA, has a huge impact on gene expression in pathogenic E. coli strains, its effect on virulence is ambiguous. At a high infection dose, hns mutants trigger more sudden lethality due to their increased acute toxicity in murine urinary tract infection and sepsis models. At a lower infectious dose, however, mutants lacking H-NS are attenuated through their impaired growth rate, which can only partially be compensated for by the higher expression of numerous virulence factors.Uropathogenic Escherichia coli (UPEC) is the leading cause of uncomplicated urinary tract infections, the most common bacterial infection in industrialized countries (28). The ability of these pathogenic variants to colonize the urinary tract is linked to the presence of virulence factors encoded by horizontally acquired genes not present in their nonpathogenic relatives. These factors include adhesins, cytotoxins, iron uptake systems, capsular polysaccharide, and serum resistance. In E. coli strain 536 (

Regulation of Expression of Uropathogenic Escherichia coli Nonfimbrial Adhesin TosA by PapB Homolog TosR in Conjunction with H-NS and Lrp

“…TosA levels were dramatically increased in the ⌬hns background compared to wild-type CFT073, suggesting that H-NS could function as a negative regulator of the tos operon. However, it is important to note that H-NS perturbs the expression of a number of different genes (22,43,(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57); therefore, it remains unclear if additional regulators supplement H-NS-mediated negative regulation of the tos operon. The loss of Lrp failed to increase tos operon expression, as was observed for loss of H-NS.…”

“…PAIs are often identified by their AT richness (41,(43)(44)(45), and AT-rich genes and PAIs are often silenced by H-NS (41,43,44). In addition, H-NS also contributes to negative regulation of adhesin operons and dual regulation of motility operons (38,(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58). Indeed, PapB was previously suggested to mediate positive regulation of the pap operon by anti-silencing H-NS repression (58).…”

Uropathogenic Escherichia coli CFT073 Is Adapted to Acetatogenic Growth but Does Not Require Acetate during Murine Urinary Tract Infection

“…A probable role for acetyl phosphate metabolism in extraintestinal, gram-negative pathogenesis is in the indirect effect acetyl phosphate has on the histone-like protein H-NS (21). H-NS is capable of repressing numerous processes, often associated with horizontally acquired DNA that plays a role in pathogenesis (5,14,16,17,23,27,34). UPEC 536 hns upregulated numerous virulence factors (34) similarly to a CFT073 mutant that colonizes the murine urinary tract in a robust fashion (19).…”

New insights into transcriptional regulation by H-NS

“…Consequently the heterodimer form of StpA is predominant. A mutation in stpA has no discernable phenotype on its own in E. coli but derepresses a subset of genes in the absence of H-NS [32]. StpA can repress its own expression but cannot repress the bgl operon unless at least the N-terminus of H-NS is present to allow formation of heterodimers [33].…”