Finding Order in the Chaos: Outstanding Questions in Klebsiella pneumoniae Pathogenesis

Abstract

Klebsiella pneumoniae are gram-negative facultative anaerobes that are found within host-associated commensal microbiomes, but they can also cause a wide range of infections that are often difficult to treat. These infections are caused by different pathotypes of K. pneumoniae, called either classical and hypervirulent strains. These two strain groups are genetically distinct, inhabit non-overlapping geographies, and cause different types of harmful infections in humans. These distinct bacterial groups have also been found to interact differently with the host immune system. Initial innate immune defenses against K. pneumoniae infection include complement, macrophages, neutrophils, and monocytes; these defenses are primary strategies employed by the host to clear infections. K. pneumoniae pathogenesis depends upon the interactions between the microbe and each of these host defenses, and it is becoming increasingly apparent that bacterial genetic diversity impacts the outcomes of these interactions. Herein we highlight recent advances in our understanding of K. pneumoniae pathogenesis, with a focus on how bacterial evolution and diversity impact K. pneumoniae interactions with mammalian innate immune host defenses. We also discuss outstanding questions regarding how K. pneumoniae can frustrate normal immune responses, capitalize upon states of immunocompromise, and cause infections with high mortality.

From Klebsiella pneumoniae Colonization to Dissemination: An Overview of Studies Implementing Murine Models

“…Fulfilling Koch's postulate, the combined effects of the overproduction of the virulence factors and a high degree of phagocytosis resistance seem to be very useful in the dissemination of hvKp. The interactions with host immunity are largely related to capsule polysaccharides and to the virulence of the strains (e g cKp or hvKp) which is dependant of the bacterial accessory genome [6,62].…”

“…Klebsiella pneumoniae is a Gram-negative non-motile and encapsulated bacterium found in environmental conditions as diverse as soil, plant leaves, mammalian intestines, and waste waters [1,2]. It is an opportunistic pathogen that is able to colonize the mucosal epithelium of the gut and nasopharynx and to disseminate into the deep tissues and bloodstreams of susceptible patients, causing severe infections such as pneumonia, meningitis, endophthalmitis, pyogenic liver abscesses, and bacteremia [3][4][5][6]. The ability of this bacterium to form a biofilm on invasive medical devices leads to subsequent health care associated infections, particularly in the urinary and pulmonary tracts [4].…”

“…The association between the clinical phenotype and the genomic variations is hard to elucidate because of an intensive gene-content turnover between the strains, both in the core and accessory genomes [10]. Clinical strains of K. pneumoniae can be divided into two main categories: the classical group (cKp) comprising of MDR strains, and the hypervirulent (hvKp) group of strains [6]. cKp strains are usually hosted in the gastrointestinal (GI) tract of patients with intestinal portage, the incidences of which are estimated to be between 6 and 19% [9,11].…”

“…HvKp strains are emerging variants of cKp that, unlike cKp strains, cause organ and life-threatening infections even in healthy immunocompetent individuals. hvKp strains are considered as strict pathogens that cause infections at multiple sites including pyogenic liver abscesses, pneumonia, endophthalmitis, meningitis, and necrotizing fasciitis followed by metastatic spreading [6,16]. The specific traits of hvKp were discussed in depth in a recent review published by Russo and Marr [17].…”

“…Several in vitro studies have characterized the pathogenicity of K. pneumoniae strains and described the underlying molecular mechanisms and their immune evasion strategies [6]. The development of innovative in vitro models is promising, but the complexity of the host physiology (immunity, microbiota, and the dynamics of physico-chemical conditions) is often difficult to reproduce in a single in vitro model.…”