Phylogenetic Analysis of<i>Klebsiella pneumoniae</i>from Hospitalized Children, Pakistan

Ejaz, Hasan; Wang, Nancy; Wilksch, Jonathan J.; Page, Andrew J.; Cao, Hanwei; Gujaran, Shruti; Keane, Jacqueline A.; Lithgow, Trevor; ul-Haq, Ikram; Dougan, Gordon; Strugnell, Richard A.; Heinz, Eva

doi:10.3201/eid2311.170833

Cited by 39 publications

(49 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For OmpK35, premature stop codons were detected in 772 (29%) gene products (Table S1). These terminating mutations are found throughout the phylogeny but were enriched in the dominant lineage of K. pneumoniae CC258 and strains from a recent survey of a major hospital in Pakistan (42) (Fig. 1A).…”

Section: Resultsmentioning

confidence: 95%

Global Trends in Proteome Remodeling of the Outer Membrane Modulate Antimicrobial Permeability in Klebsiella pneumoniae

Rocker

Lacey

Belousoff

et al. 2020

mBio

Self Cite

View full text Add to dashboard Cite

In Gram-negative bacteria, the permeability of the outer membrane governs rates of antibiotic uptake and thus the efficacy of antimicrobial treatment. Hydrophilic drugs like β-lactam antibiotics depend on diffusion through pore-forming outer membrane proteins to reach their intracellular targets. In this study, we investigated the distribution of porin genes in more than 2,700 Klebsiella isolates and found a widespread loss of OmpK35 functionality, particularly in those strains isolated from clinical environments. Using a defined set of outer-membrane-remodeled mutants, the major porin OmpK35 was shown to be largely responsible for β-lactam permeation. Sequence similarity network analysis characterized the porin protein subfamilies and led to discovery of a new porin family member, OmpK38. Structure-based comparisons of OmpK35, OmpK36, OmpK37, OmpK38, and PhoE showed near-identical pore frameworks but defining differences in the sequence characteristics of the extracellular loops. Antibiotic sensitivity profiles of isogenic Klebsiella pneumoniae strains, each expressing a different porin as its dominant pore, revealed striking differences in the antibiotic permeability characteristics of each channel in a physiological context. Since K. pneumoniae is a nosocomial pathogen with high rates of antimicrobial resistance and concurrent mortality, these experiments elucidate the role of porins in conferring specific drug-resistant phenotypes in a global context, informing future research to combat antimicrobial resistance in K. pneumoniae. IMPORTANCE Klebsiella pneumoniae is a pathogen of humans with high rates of mortality and a recognized global rise in incidence of carbapenem-resistant K. pneumoniae (CRKP). The outer membrane of K. pneumoniae forms a permeability barrier that modulates the ability of antibiotics to reach their intracellular target. OmpK35, OmpK36, OmpK37, OmpK38, PhoE, and OmpK26 are porins in the outer membrane of K. pneumoniae, demonstrated here to have a causative relationship to drug resistance phenotypes in a physiological context. The data highlight that currently trialed combination treatments with a carbapenem and β-lactamase inhibitors could be effective on porin-deficient K. pneumoniae. Together with structural data, the results reveal the role of outer membrane proteome remodeling in antimicrobial resistance of K. pneumoniae and point to the role of extracellular loops, not channel parameters, in drug permeation. This significant finding warrants care in the development of phage therapies for K. pneumoniae infections, given the way porin expression will be modulated to confer phage-resistant—and collateral drug-resistant—phenotypes in K. pneumoniae.

show abstract

Section: Resultsmentioning

confidence: 95%

Global Trends in Proteome Remodeling of the Outer Membrane Modulate Antimicrobial Permeability in Klebsiella pneumoniae

Rocker

Lacey

Belousoff

et al. 2020

mBio

Self Cite

View full text Add to dashboard Cite

show abstract

“…The dominance of four globally important clones (STs: 15; 101; 307; 874) amongst the K. pneumoniae at CUH (41%) (Additional file 1: Figure S3A; Additional file 2: Table S1) was led by ST15 which is strongly linked to outbreaks in hospitals [8,17,18]. ST101 has been highlighted for its association with extensive resistance and KPC carbapenemases [19], and ST307 was reported in a recent large-scale analysis of carbapenem-resistant isolates [20,21].…”

Section: K Pneumoniae and Enterobacter Represented Flowing Vs Staticmentioning

confidence: 99%

Contrasting patterns of longitudinal population dynamics and antimicrobial resistance mechanisms in two priority bacterial pathogens over 7 years in a single center

et al. 2019

Self Cite

View full text Add to dashboard Cite

Background: Two of the most important pathogens contributing to the global rise in antimicrobial resistance (AMR) are Klebsiella pneumoniae and Enterobacter cloacae. Despite this, most of our knowledge about the changing patterns of disease caused by these two pathogens is based on studies with limited timeframes that provide few insights into their population dynamics or the dynamics in AMR elements that they can carry. Results: We investigate the population dynamics of two priority AMR pathogens over 7 years between 2007 and 2012 in a major UK hospital, spanning changes made to UK national antimicrobial prescribing policy in 2007. Between 2006 and 2012, K. pneumoniae showed epidemiological cycles of multi-drug-resistant (MDR) lineages being replaced approximately every 2 years. This contrasted E. cloacae where there was no temporally changing pattern, but a continuous presence of the mixed population. Conclusions: The differing patterns of clonal replacement and acquisition of mobile elements shows that the flux in the K. pneumoniae population was linked to the introduction of globally recognized MDR clones carrying drug resistance markers on mobile elements. However, E. cloacae carries a chromosomally encoded ampC conferring resistance to front-line treatments and shows that MDR plasmid acquisition in E. cloacae was not indicative of success in the hospital. This led to markedly different dynamics in the AMR populations of these two pathogens and shows that the mechanism of the resistance and its location in the genome or mobile elements is crucial to predict population dynamics of opportunistic pathogens in clinical settings.

show abstract

“…similipneumoniae (previously KPIIB), K. variicola (previously KPIII) [5], as well as two strains forming divergent lineages indicating potentially novel species within this species complex [6]. Whole genome sequencing (WGS) has shown that the predominant cause of clinical infection worldwide has been K. pneumoniae (KpI) [5] but there is an increasing trend, and increasing concern, in the detection of severe cases due to the newly described species [7]. Different studies report K. quasipneumoniae isolates causing infections resistant to treatments with ceftazidime and other oxyimino-betalactam antibiotics, and widespread carriage of genes encoding carbapenemase (KPC) [3,4,[8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Forensic genomics of a novel Klebsiella quasipneumoniae type from a neonatal intensive care unit in China reveals patterns of colonization, evolution and epidemiology

Perlaza-Jiménez

Torres

et al. 2020

Microbial Genomics

Self Cite

View full text Add to dashboard Cite

During March 2017, a neonatal patient with severe diarrhoea subsequently developed septicaemia and died, with Klebsiella isolated as the causative microorganism. In keeping with infection control protocols, the coincident illness of an attending staff member and three other neonates with Klebsiella infection triggered an outbreak response, leading to microbiological assessment of isolates collected from the staff member and all 21 co-housed neonates. Multilocus sequence typing and genomic sequencing identified that the isolates from the 21 neonates were of a new Klebsiella sequence type, ST2727, and taxonomically belonged to K. quasipneumoniae subsp. similipneumoniae (formerly referred to as KpIIB). Genomic characterization showed that the isolated ST2727 strains had diverged from other K. quasipneumoniae subsp. similipneumoniae strains at least 90 years ago, whereas the neonatal samples were highly similar with a genomic divergence of 3.6 months. There was no relationship to the Klebsiella isolate from the staff member. This demonstrates that no transmission occurred from staff to patient or between patients. Rather, the data suggest that ST2727 colonized each neonate from a common hospital source. Sequence-based analysis of the genomes revealed several genes for antimicrobial resistance and some virulence features, but suggest that ST2727 is neither extremely-drug resistant nor hypervirulent. Our results highlight the clinical significance and genomic properties of ST2727 and urge genome-based measures be implemented for diagnostics and surveillance within hospital environments. Additionally, the present study demonstrates the need to scale the power of genomic analysis in retrospective studies where relatively few samples are available.

show abstract

Phylogenetic Analysis ofKlebsiella pneumoniaefrom Hospitalized Children, Pakistan

Cited by 39 publications

References 12 publications

Global Trends in Proteome Remodeling of the Outer Membrane Modulate Antimicrobial Permeability in Klebsiella pneumoniae

Global Trends in Proteome Remodeling of the Outer Membrane Modulate Antimicrobial Permeability in Klebsiella pneumoniae

Contrasting patterns of longitudinal population dynamics and antimicrobial resistance mechanisms in two priority bacterial pathogens over 7 years in a single center

Forensic genomics of a novel Klebsiella quasipneumoniae type from a neonatal intensive care unit in China reveals patterns of colonization, evolution and epidemiology

Contact Info

Product

Resources

About