The high-pathogenicity island (HPI) promotes flagellum-mediated motility in extraintestinal pathogenic Escherichia coli

Abstract

The key of success of extraintestinal pathogenic Escherichia coli (ExPEC) to colonize niches outside the intestinal tract and to establish infection is the coordinated action of numerous virulence and fitness factors. The so-called high-pathogenicity island (HPI), responsible for synthesis, secretion and uptake of the siderophore yersiniabactin, proved to be an important virulence determinant. In this study we investigated the interaction of the flagellum-mediated motility and the HPI. The impairment of yersiniabactin production by deletion of irp2 or ybtA affected significantly motility. The gain of yersiniabactin production improved motility in both pathogenic and non-pathogenic E. coli strains. The loss of flagella expression had no adverse effect on the HPI. Strikingly, external iron abundance was not able to suppress activation of the HPI during motility. The HPI activity of swarming bacteria was comparable to iron deplete conditions, and could even be maximized by supplementing excessive iron. This fact is the first description of a regulatory mechanism, which does not follow the known hierarchical regulation of siderophore systems. Transcriptional reporter fusions of the ybtA promoter demonstrated that the entire promoter region with all YbtA binding sites is necessary for complete induction in both HPI-positive and HPI-negative strains. Altogether, these results suggest that the HPI is part of a complex regulatory network, which orchestrates various virulence mechanisms to optimize the overall fitness of ExPEC.

Two Polyketides Intertwined in Complex Regulation: Posttranscriptional CsrA-Mediated Control of Colibactin and Yersiniabactin Synthesis in Escherichia coli

“…FyuA is an HPI-encoded outer membrane protein, playing an important role in the virulence of ExPEC ( 12 – 19 ). Investigation of the role of the HPI in E. coli gene regulation also indicated a connection between motility and yersiniabactin expression, suggesting the interplay between the flagellar regulatory system and the promoter region of the major HPI regulator YbtA ( 15 , 20 , 21 ).…”

“…The co-occurrence and physical linkage of the pks island and the HPI, together with their common Fur-dependent regulation, the role of the HtpG chaperone for the production of colibactin and yersiniabactin, and the importance of the pks island-encoded PPTase ClbA for yersiniabactin expression demonstrate the close relationship between these two islands coding for secondary metabolites contributing to the fitness of extraintestinal pathogenic and commensal E. coli . Against this background, the findings that yersiniabactin expression is affected by motility regulation ( 15 ) and that uropathogenic E. coli (UPEC) model strain 536 and its spontaneous nonhemolytic pathogenicity island I and II deletion mutant 536-21 ( 47 ) appeared to be phenotypically colibactin negative despite carrying an intact pks island led us to further investigate the regulation of colibactin and yersiniabactin expression. We applied reporter gene constructs and electrophoretic mobility shift assays, as well as different phenotypic analyses in different strain backgrounds, to demonstrate the complex dependencies inside this regulatory network.…”

Iron influences the expression of colonization factor CS6 of enterotoxigenic Escherichia coli

“…The expression of virulence factors had shown to be regulated by iron availability in an earlier study [28]. A rise in the expression of flagellin production with additional iron was also seen for extraintestinal pathogenic Escherichia coli [29]. Iron increases the synthesis and surface placement of adhesins in trichomonas [30].…”

New insights into the construction of wild-type Saba pig-derived Escherichia coli irp2 gene deletion strains

“…Saba pig is an excellent local breeding pig in Yunnan province in China, with wide distribution and large quantity, and is listed as a national livestock and poultry genetic resource protection breed (Lian et al 2006). For a long time, due to inadequate feeding management and disease prevention and control, diarrhea and death caused by pathogenic E. coli infection in Saba pigs has become an important factor seriously threatening the development of characteristic pig industry in Yunnan province.…”

“…HPI has a 30.5 kb functional core regions and carries irp1 - irp9 genes related to iron element syntheses, regulation and uptake. Irp2 as a marker gene of HPI is an iron-regulated gene, which is only expressed in pathogenic bacteria and plays an important role in the syntheses of iron carriers and synthesis yersiniabactin (Ybt) (Tu et al 2016 ; Magistro et al 2017 ). Irp2 expresses the high molecular weight protein 2 (HMWP2), which is mainly involved in siderophore and induces the expression of ironophore.…”