A Metabolic Operon in Extraintestinal PathogenicEscherichia coliPromotes Fitness under Stressful Conditions and Invasion of Eukaryotic Cells

Abstract

We identified a carbohydrate metabolic operon (frz) that is highly associated with extraintestinal pathogenic Escherichia coli (ExPEC) strains. The frz operon codes for three subunits of a phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) transporter of the fructose subfamily, for a transcriptional activator of PTSs of the MgA family, for two type II ketose-1,6-bisphosphate aldolases, for a sugar-specific kinase (repressor, open reading frame, kinase family [ROK]), and for a protein of the cupin superfamily. We proved that the frz operon promotes bacterial fitness under stressful conditions, such as oxygen restriction, late stationary phase of growth, or growth in serum or in the intestinal tract. Furthermore, we showed that frz is involved in adherence to and internalization in human type II pneumocytes, human enterocytes, and chicken liver cells by favoring the ON orientation of the fim operon promoter and thus acting on the expression of type 1 fimbriae, which are the major ExPEC adhesins. Both the PTS activator and the metabolic enzymes encoded by the frz operon are involved in these phenotypes.

The Bacterial Phosphoenolpyruvate:Carbohydrate Phosphotransferase System: Regulation by Protein Phosphorylation and Phosphorylation-Dependent Protein-Protein Interactions

“…Horizontal gene transfer probably also explains the presence of PRD-containing regulators in a few spirochaetes (treponemae and brachyspirae). Interestingly, in several pathogenic E. coli strains, genes encoding PRD-containing regulators are sometimes located in pathogenicity islands (55), which also supports the concept of horizontal gene transfer.…”

“…There are also numerous proteins of unknown function that contain a PTS domain (6). The PTS-mediated regulation of the lactose transporters from Streptococcus thermophilus (53) and Streptococcus salivarius (54) and of several transcription activators from firmicutes (1) and some Enterobacteriaceae, such as FrzR of E. coli (55), has been studied in detail.…”

Diagnostic Strategy for Identifying Avian Pathogenic Escherichia coli Based on Four Patterns of Virulence Genes

“…It has recently been shown in an APEC strain of serogroup O1 that P fimbriae are involved in the virulence of that strain in chickens (35). Gene frz orf4 is chromosomally located and belongs to the frz operon, which encodes a phosphoenolpyruvate carbohydrate phosphotransferase system transporter and enzymes involved in sugar metabolism (48). A link between the expression of this locus and E. coli pathogenic abilities was confirmed by experiments showing its role in promoting bacterial fitness under stressful conditions, such as oxygen restriction or the late stationary phase of growth, and in promoting growth in chicken serum or the intestinal tract during in vivo competition assays.…”

“…Several virulence genes have been demonstrated to be implicated in avian colibacillosis, including those encoding for adhesins (F1, P, and Stg fimbriae, curli, and EA/I), anti-host defense factors (OmpA, Iss, lipopolysaccharide, and K1), iron acquisition systems (aerobactin, Iro proteins, yersiniabactin, and the Sit iron acquisition locus), autotransporters (Tsh, Vat, and AatA), the phosphate transport system, sugar metabolism, and the IbeA protein (1,12,13,24,35,38,48).…”

TheKlebsiella pneumoniaeYfgL (BamB) lipoprotein contributes to outer membrane protein biogenesis, type-1 fimbriae expression, anti-phagocytosis, andin vivovirulence

“…In this context, we noted that one early study indicated that a PTS system is involved in type-1 fimbriae expression in extraintestinal pathogenic E. coli (ExPEC). 33 We therefore sought to determine whether the NTUH-K2044 kp0760-kp0763 gene cluster (which, as noted above, encodes a PTS system and is positively affected by YfgL) was involved in type-1 fimbriae expression. We compared the fim phase switching of the yfgL mutant with that of the wild-type strain; the yfgL complementation strain; and a pts mutant (kp0760-kp0763) strain.…”