Regulation of Escherichia coli Group 2 Capsule Gene Expression: A Mini Review and Update

Abstract

The expression of a group 2 capsule (K antigen), such as the K1 or K5 antigen, is a key virulence factor of Escherichia coli responsible for extra-intestinal infections. Capsule expression confers resistance to innate host defenses and plays a critical role in invasive disease. Capsule expression is temperature-dependent being expressed at 37°C but not at 20°C when outside the host. Group 2 capsule gene expression involves two convergent promoters PR1 and PR3, the regulation of which is critical to capsule expression. Temperature-dependent expression is controlled at transcriptional level directly by the binding of H-NS to PR1 and PR3 and indirectly through BipA with additional input from IHF and SlyA. More recently, other regulatory proteins, FNR, Fur, IHF, MprA, and LrhA, have been implicated in regulating capsule gene expression in response to other environmental stimuli and there is merging data for the growth phase-dependent regulation of the PR1 and PR3 promoters. The aim of the present Mini Review is to provide a unified update on the latest data on how the expression of group 2 capsules is regulated in response to a number of stimuli and the growth phase something that has not to date been addressed.

Keywords: BipA; H-NS; IHF; K1 capsule; PR1 promoter; SlyA; UTI.

Figure 1

Genetic organization of Escherichia coli group 2 (K1) kps gene cluster. Group 2 kps clusters have two conserved regions 1 and 3 which are flank the serotype-specific region 2. Region 1 and 3 promoters (PR1 and PR3) are denoted by bent arrows. PR1 drives the transcription to region 1 genes while PR3 drives the transcription to region 3 genes and reads through to region 2 genes by RfaH antiterminator (white circle). The lower half of the figure dissects the PR1 and PR3 promoters. PR1 promoter contains three tandem promoters (PR1-1, PR1-2, and PR1-3) and the IHF (pink circle) binds to its consensus sequence at +140 while H-NS (blue circles) binds to three consensus sequences H-NS I, II, and III from position −224 to −134, −121 to −79, and +1 to +32. SlyA (green border white circles) and H-NS both bind to the H-NS I and II sites upstream of PR1-1 and the binding is not mutually exclusive. H-NS protects PR3 regions from −135 to −21 and +141 to +219 relative to transcription start site and SlyA overlaps H-NS upstream of PR1-3. Numbering indicates the position of the nucleotide relative to the transcription start site (modified from Aldawood, 2019).

Figure 2

Schematic representation of the predicted regulation of the PR1 region of E. coli K1 by growth phase. Various regulatory proteins bind to the PR1 region that could activate (arrow pointing up) or repress (arrow pointing down) the transcription from the corresponding promoter at certain growth phase. The question mark denotes unknown regulator/regulators. IHF acts both directly and indirectly in regulating transcription from PR1. Indirectly, through as yet unknown protein(s), it activates both PR1-1 at early and mid-exponential phase and PR1-2 at the late exponential phase. In contrast by directly at +140, it represses PR1-2 and PR1-3 at stationary phase. H-NS I, II, and III denote the H-NS protected regions spanning through PR1 promoter from position −224 to −134, −121 to −79, and +1 to +32. SlyA overlaps H-NS upstream of PR1-1 but the binding is not mutually exclusive.