Hypermucoviscosity in Klebsiella pneumoniae: manifestation, regulation, and roles in pathogenesis.

In recent years, Klebsiella pneumoniae (Kpn) has evolved into a global public health threat. Convergent Kpn lineages that are both hypervirulent and multidrug-resistant have emerged and can cause community-acquired, drug-resistant infections, with increased mortality. A major driver of hypervirulence in Kpn is hypermucoviscosity (HMV), a phenotype historically associated with increased capsular polysaccharide (CPS) production. Recent findings show that HMV is a distinct trait characterized by increased CPS chain length and uniformity, rather than by overproduction of CPS. The regulators of mucoid phenotype (RmpADC and/or RmpA2) have traditionally been characterized as determinants of HMV. However, recent evidence suggests that Kpn can also manifest HMV independently of the regulators of mucoid phenotype, driven by missense mutations in the wzc gene of the CPS biosynthesis locus. These findings have immense ramifications, as non-hypervirulent Kpn lineages can rapidly enhance their virulence and invasiveness by acquiring wzc mutations and manifesting HMV. Since HMV confers Kpn with the ability to adhere poorly to immune cells and resist phagocytosis, it enables systemic dissemination. This benefit, however, appears to be niche specific, as HMV hinders adhesion to epithelial cells and biofilm formation on medical devices, traits which may be beneficial in some niches. Kpn tackles this problem by fine-tuning HMV expression via switches driven by mutations or through regulatory control in response to environmental cues. This review synthesizes recent findings on the molecular mechanisms by which HMV is manifested, is intricately regulated, and how HMV contributes to Kpn's success in diverse infection niches, such as the respiratory tract, bloodstream, and urinary tract.