Deciphering the role of the capsule of Klebsiella pneumoniae during pathogenesis: A cautionary tale

Abstract

Extracellular capsule polysaccharides increase the cellular fitness under abiotic stresses and during competition with other bacteria. They are best‐known for their role in virulence, particularly in human hosts. Specifically, capsules facilitate tissue invasion by enhancing bacterial evasion from phagocytosis and protect cells from biocidal molecules. Klebsiella pneumoniae is a worrisome nosocomial pathogen with few known virulence factors, but the most important one is its capsule. In this issue, Tan et al. assess the fitness advantage of the capsule by competing a wild‐type strain against four different mutants where capsule production is interrupted at different stages of the biosynthetic pathway. Strikingly, not all mutants provide a fitness advantage. They suggest that some mutants have secondary defects altering virulence‐associated phenotypes and blurring the role of the capsule in pathogenesis. This study indicates that the K1 capsule in K. pneumoniae is not required for gut colonization but that it is critical for bloodstream dissemination to other organs. These results contribute to clarify the contradictory literature on the role of the Klebsiella capsule during infection. Finally, the varying fitness effects of different capsule mutations observed for K. pneumoniae K1 might apply also to other capsulated diderm bacteria that are facultative or emerging pathogens.

Selection for the bacterial capsule in the absence of biotic and abiotic aggressions depends on growth conditions

“…This might suggest that higher fitness of non-capsulated mutants in competition experiments in LB are caused by higher growth rates during exponential phase. We hypothesize that the differences in growth dynamics between Δwza and ΔwcaJ mutants are due to the periplasmic concentration of capsule percursors (Rendueles 2020, Tan et al 2020b. Overall, we propose that due to the absence of stresses, capsule inactivation or loss in rich media leads to gains in terms of growth rate and yield, as indicated by the evolution experiments, the competitions with the Δwza and ΔwcaJ mutants.…”

“…Most literature suggests that the rapid turnover of capsular serotypes is due to biotic pressures, such as phage predation, cell-to-cell interactions, the host adaptive immune system, or protozoa grazing (Cobey andLipsitch 2012, Mostowy and, but more work is needed to elucidate whether the abiotic conditions of the environment also play a role in the diversification of the capsule composition. For example, different capsules could be better adapted to certain poor environments because of their different propensity to aggregate or because of their organization at the cell surface (Phanphak et al 2019, Rendueles 2020. It could also be that different serotypes are associated to specific functions or fitness advantages (Ofek et al 1993).…”

“…This might lead to selection of serotype switching when bacteria colonize novel environments. Finally, more work is needed to elucidate capsule functions other than those that are commonly evoked and provide more insights into the non-universality of the role of capsules both within and across species (Rendueles 2020). Indeed, recent studies show that the capsule does not protect against temperate or virulent phages in K. pneumoniae, but rather the opposite, the capsule acts as a receptor for phages (de Sousa et al 2020, Tan et al 2020a).…”

L-Arginine Enhances Intracellular Killing of Carbapenem-Resistant Klebsiella pneumoniae ST258 by Murine Neutrophils

“…On the other hand, KP35 and KPPR1 harbor in their cps loci the wcaJ gene, which is absent in NJST258_1. Both, wbaP and wcaJ encode the glycosyl-transferases responsible for the initiation of capsule biosynthesis; whereas wbaP encodes a galactose-1-P transferase, wcaJ encodes a glucose-1-P transferase instead (Rendueles, 2020), and the protein products of both of these genes have implications in the evasion of phagocytosis by KP (Pal et al, 2019;Ernst et al, 2020). Deletion of wcaJ promoted biofilm formation and allowed KP to evade macrophage phagocytosis and oxidative killing in vitro (Pal et al, 2019).…”

A Molecular Interaction Map of Klebsiella pneumoniae and Its Human Host Reveals Potential Mechanisms of Host Cell Subversion

“…There are mainly four types of virulence factors in K. pneumoniae : (i) capsule ( Struve and Krogfelt, 2003 ; Schembri et al, 2005 ; Evrard et al, 2010 ; Rendueles, 2020 ), (ii) fimbriae ( Murphy et al, 2013 ; Lin et al, 2017 ), (iii) lipopolysaccharides ( Kamaladevi and Balamurugan, 2016 ), and (iv) siderophores ( Holden et al, 2016 , 2018 ; Zhang et al, 2017 ) that have been well studied and are important for virulence in infection models. However, there are several genes in the K. pneumoniae genome that remain poorly characterized and might have potential roles in virulence ( Pranavathiyani et al, 2020 ).…”