Colonization, Infection, and the Accessory Genome of Klebsiella pneumoniae

Abstract

Klebsiella pneumoniae is a Gram-negative pathogen that has a large accessory genome of plasmids and chromosomal gene loci. This accessory genome divides K. pneumoniae strains into opportunistic, hypervirulent, and multidrug-resistant groups and separates K. pneumoniae from two closely related species, Klebsiella variicola and Klebsiella quasipneumoniae. Some strains of K. pneumoniae act as opportunistic pathogens, infecting critically ill and immunocompromised patients. These K. pneumoniae are a common cause of health-care associated infections including pneumonia, urinary tract infections (UTIs), and bloodstream infections. K. variicola and K. quasipneumoniae are often clinically indistinguishable from opportunistic K. pneumoniae. Other strains of K. pneumoniae are hypervirulent, infecting healthy people in community settings and causing severe infections including pyogenic liver abscess, endophthalmitis, and meningitis. A third group of K. pneumoniae encode carbapenemases, making them highly antibiotic-resistant. These strains act as opportunists but are exceedingly difficult to treat. All of these groups of K. pneumoniae and related species can colonize the gastrointestinal tract, and the accessory genome may determine if a colonizing strain remains asymptomatic or progresses to cause disease. This review will explore the associations between colonization and infection with opportunistic, antibiotic-resistant, and hypervirulent K. pneumoniae strains and the role of the accessory genome in distinguishing these groups and related species. As K. pneumoniae infections become progressively more difficult to treat in the face of antibiotic resistance and hypervirulent strains, an increased understanding of the epidemiology and pathogenesis of these bacteria is vital.

Epidemiology of respiratory pathogen carriage in the homeless population within two shelters in Marseille, France, 2015–2017: cross sectional 1-day surveys

“…Klebsiella pneumoniae nasopharyngeal carriage rates have been reported to range from 3% to 15%, which is in agreement with our results [25]. This bacterium is known to be frequently multidrug-resistant [25] and further studies on drug resistance in bacteria isolated from homeless people would be of interest.…”

“…A 2.3% H. influenzae nasal prevalence was observed in Marseille's individuals originating from North Africa using quantitative PCR in 2013 [17]; however, the survey was conducted in October, which may account for a lower prevalence, as shown in another healthy Italian children population [24]. Klebsiella pneumoniae nasopharyngeal carriage rates have been reported to range from 3% to 15%, which is in agreement with our results [25]. This bacterium is known to be frequently multidrug-resistant [25] and further studies on drug resistance in bacteria isolated from homeless people would be of interest.…”

Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from south and southeast Asia

“…Whilst the picture of K. pneumoniae pathogenesis is incomplete, isolates harbouring one or more key virulence determinants (including RmpA/RmpA2, which upregulate capsule expression; the colibactin genotoxin; and the yersiniabactin, aerobactin and salmochelin siderophores that promote systemic survival and dissemination 13 ) are more commonly associated with invasive disease 14,15 . Isolates that contain several of these determinants are associated with severe community--acquired invasive disease, often manifesting as liver abscess with bacteraemia.…”

Antibody-Recruiting Protein-Catalyzed Capture Agents to Combat Antibiotic-Resistant Bacteria

“…A literature search (see Methods section for specific references) then narrowed the selection by prioritizing essential virulence-and pathogenicity-related genes as well as protein orientation in the outer membrane, to five proteins: (i) FhuA, a siderophore, (ii) Lpp, a lipoprotein, (iii) Pal, a peptidoglycan-associated lipoprotein, (iv) NlpD, a lipoprotein, (v) MrkA, a subunit of the type 3 fimbriae. Ultimately, MrkA was chosen as a target due to its key roles in infection and persistence, (44) its presence in the majority of sequenced K. pneumoniae strains, (45)(46)(47) and, critically, its location in fimbrial rods. These rods are large extracellular structures (0.5-2 µm long, 4-to-5 nm in diameter) (48,49) that are each comprised of up to 1,000s of MrkA copies.…”