The intersection of capsule gene expression, hypermucoviscosity and hypervirulence in Klebsiella pneumoniae

Abstract

For ∼30 years, two distinct groups of clinical isolates of Klebsiella pneumoniae have been recognized. Classical strains (cKp) are typically isolated from patients with some degree of immunocompromise and are not virulent in mouse models of infection whereas hypervirulent strains (hvKp) are associated with community acquired invasive infections and are highly virulent in mouse models of infection. Hyperproduction of capsule and a hypermucoviscous colony phenotype have been strongly associated with the hypervirulence of hvKp strains. Recent studies have begun to elucidate the relationship between capsule gene expression, hypermucoviscosity and hypervirulence. Additionally, genes associated with hyperproduction of capsule and hypermucoviscosity in hvKp strains have been identified in a few cKp isolates. However, it is not clear how the acquisition of these genes impacts the virulence of cKp isolates. A better understanding of the potential risks of these strains is particularly important given that many of them are resistant to multiple antibiotics, including carbapenems.

Figure 1

Schematic of the capsule locus in KPPR1S. The three characterized promoters are indicated upstream of galF (also referred to as orf 1–2), wzi (orf 3–15) and manC (orf 16–17). Genes in dark blue are highly conserved among different capsule types; those in light blue are capsule type-specific, and those in dark blue hatches can vary depending on the sugar precursors that comprise the capsule. Orfs 12 and 13 appear to be unique to Klebsiella.

Figure 2

Complex matrix of capsule regulation. Each shape represents a different transcriptional regulator known to contribute in some way to the expression of capsule biosynthetic genes. If known or logically presumed, dimerization is indicated by doublets. Arrow thickness indicates the relative impact of the regulator: thin, small fold-change in mutant strain; thicker, larger fold-change in mutant strain. Arrows indicate activators, and T-shaped lines indicate repressors. Solid lines indicate that direct binding has been demonstrated for at least one of the cps promoters, and dashed lines indicate direct binding has not been tested. Italicized proteins have been characterized in only a single K. pneumoniae strain whereas the others have been characterized in at least 2 strains.