Evolution of Outbreak-Causing Carbapenem-Resistant Klebsiella pneumoniae ST258 at a Tertiary Care Hospital over 8 Years DOI Creative Commons
Jane W. Marsh, Mustapha M. Mustapha, M. Patrick Griffith

et al.

mBio, Journal Year: 2019, Volume and Issue: 10(5)

Published: Sept. 4, 2019

The carbapenem class of antibiotics is invaluable for the treatment selected multidrug-resistant Gram-negative pathogens. continued transmission carbapenem-resistant bacteria such as ST258 K. pneumoniae serious global public health concern, options these infections are limited. This genomic epidemiologic investigation traced natural history in a single care setting over nearly decade. We found that distinct subpopulations have caused both device-associated and ward-associated outbreaks, some populations remain endemic within our hospital to present day. finding virulence determinants among emergent clones supports idea convergent evolution drug-resistant virulent CRKP strains highlights need surveillance, prevention, control efforts address evolving setting.

Language: Английский

Hypervirulent Klebsiella pneumoniae DOI Open Access
Thomas A. Russo,

Candace Marr

Clinical Microbiology Reviews, Journal Year: 2019, Volume and Issue: 32(3)

Published: May 23, 2019

Hypervirulent K. pneumoniae (hvKp) is an evolving pathotype that more virulent than classical (cKp). hvKp usually infects individuals from the community, who are often healthy. Infections common in Asian Pacific Rim but occurring globally. infection frequently presents at multiple sites or subsequently metastatically spreads, requiring source control. has increased ability to cause central nervous system and endophthalmitis, which require rapid recognition site-specific treatment. The genetic factors confer hvKp's hypervirulent phenotype present on a large virulence plasmid perhaps integrative conjugal elements. Increased capsule production aerobactin established hvKp-specific factors. Similar cKp, strains becoming increasingly resistant antimicrobials via acquisition of mobile elements carrying resistance determinants, new emerge when extensively drug-resistant cKp acquire resulting nosocomial infection. Presently, clinical laboratories unable differentiate hvKp, recently, several biomarkers quantitative siderophore have been shown accurately predict strains, could lead development diagnostic test for use by optimal patient care epidemiologic surveillance research studies.

Language: Английский

Citations

853

Population genomics of Klebsiella pneumoniae DOI Open Access
Kelly L. Wyres, Margaret M. C. Lam, Kathryn E. Holt

et al.

Nature Reviews Microbiology, Journal Year: 2020, Volume and Issue: 18(6), P. 344 - 359

Published: Feb. 13, 2020

Language: Английский

Citations

768

A genomic surveillance framework and genotyping tool for Klebsiella pneumoniae and its related species complex DOI Creative Commons
Margaret M. C. Lam, Ryan R. Wick, Stephen C. Watts

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: July 7, 2021

Abstract Klebsiella pneumoniae is a leading cause of antimicrobial-resistant (AMR) healthcare-associated infections, neonatal sepsis and community-acquired liver abscess, associated with chronic intestinal diseases. Its diversity complex population structure pose challenges for analysis interpretation K. genome data. Here we introduce Kleborate, tool analysing genomes its species complex, which consolidates interrogation key features proven clinical importance. Kleborate provides framework to support genomic surveillance epidemiology in research, public health settings. To demonstrate utility apply analyse publicly available genomes, including isolates from pan-European study carbapenemase-producing , highlighting global trends AMR virulence as examples what could be achieved by applying this within more systematic efforts. We also the application detect type gut metagenomes.

Language: Английский

Citations

647

Hypervirulent Klebsiella pneumoniae – clinical and molecular perspectives DOI Open Access
Jacob E. Choby, Jessica Howard‐Anderson, David S. Weiss

et al.

Journal of Internal Medicine, Journal Year: 2019, Volume and Issue: 287(3), P. 283 - 300

Published: Nov. 2, 2019

Hypervirulent Klebsiella pneumoniae (hvKp) has emerged as a concerning global pathogen. hvKp is more virulent than classical K. (cKp) and capable of causing community-acquired infections, often in healthy individuals. carried the gastrointestinal tract, which contributes to its spread community healthcare settings. First recognized Asia, arose leading cause pyogenic liver abscesses. In decades since, globally causes variety infections. addition abscesses, distinct from cKp ability metastasize distant sites, including most commonly eye, lung central nervous system (CNS). also been implicated primary extrahepatic infections bacteremia, pneumonia soft tissue The genetic determinants hypervirulence are found on large virulence plasmids well chromosomal mobile elements can be used biomarkers distinguish clinical isolates. These include up four siderophore systems for iron acquisition, increased capsule production, K1 K2 types, colibactin toxin. Additionally, strains demonstrate hypermucoviscosity, phenotypic description laboratory conditions that become distinguishing feature many hypervirulent Alarmingly, multidrug-resistant have emerged, creating new challenge combating this already dangerous

Language: Английский

Citations

441

Klebsiella pneumoniaeinfection biology: living to counteract host defences DOI Creative Commons
José A. Bengoechea, Joana Sá‐Pessoa

FEMS Microbiology Reviews, Journal Year: 2018, Volume and Issue: 43(2), P. 123 - 144

Published: Nov. 17, 2018

Klebsiella species cause a wide range of diseases including pneumonia, urinary tract infections (UTIs), bloodstream and sepsis. These are particularly problem among neonates, elderly immunocompromised individuals. is also responsible for significant number community-acquired infections. A defining feature these their morbidity mortality, the strains associated with them considered hypervirulent. The increasing isolation multidrug-resistant has significantly narrowed, or in some settings completely removed, therapeutic options treatment Not surprisingly, this pathogen then been singled out as an 'urgent threat to human health' by several organisations. This review summarises tremendous progress that made uncover sophisticated immune evasion strategies K. pneumoniae. co-evolution response challenge activated formidable exploiting stealth actively suppressing innate defences overcome host responses survive tissues. better understanding context host-pathogen interactions pivotal develop new therapeutics, which can be based on antagonising anti-immune pathogen.

Language: Английский

Citations

418

Distinct evolutionary dynamics of horizontal gene transfer in drug resistant and virulent clones of Klebsiella pneumoniae DOI Creative Commons
Kelly L. Wyres, Ryan R. Wick, Louise M. Judd

et al.

PLoS Genetics, Journal Year: 2019, Volume and Issue: 15(4), P. e1008114 - e1008114

Published: April 15, 2019

Klebsiella pneumoniae has emerged as an important cause of two distinct public health threats: multi-drug resistant (MDR) healthcare-associated infections and drug susceptible community-acquired invasive infections. These pathotypes are generally associated with subsets K. lineages or 'clones' that distinguished by the presence acquired resistance genes several key virulence loci. Genomic evolutionary analyses most notorious MDR community-associated ('hypervirulent') clones indicate differences in terms chromosomal recombination dynamics capsule polysaccharide diversity, but it remains unclear if these represent generalised trends. Here we leverage a collection >2200 genomes to identify 28 common (n ≥ 10 each), perform first genomic comparison. Eight 6 hypervirulent were identified on basis gene prevalence. Chromosomal recombination, surface locus pan-genome, plasmid phage characterised compared. The data showed highly diverse, frequent generating extensive diversity. Additional pan-genome diversity was driven acquisition/loss both plasmids phage. In contrast, rare clones, which also significant reduction largely Hence may be subject some sort constraint for horizontal transfer does not apply clones. Our findings relevant understanding risk emergence individual strains carrying genes, have been increasingly reported virulent extremely difficult treat. Specifically, our pose greatest risk, because they more likely acquire than genes.

Language: Английский

Citations

294

Characterization of antimicrobial-resistant Gram-negative bacteria that cause neonatal sepsis in seven low- and middle-income countries DOI Creative Commons
Kirsty Sands, Maria J. Carvalho, Edward Portal

et al.

Nature Microbiology, Journal Year: 2021, Volume and Issue: 6(4), P. 512 - 523

Published: March 29, 2021

Antimicrobial resistance in neonatal sepsis is rising, yet mechanisms of that often spread between species via mobile genetic elements, ultimately limiting treatments low- and middle-income countries (LMICs), are poorly characterized. The Burden Antibiotic Resistance Neonates from Developing Societies (BARNARDS) network was initiated to characterize the cause burden antimicrobial for seven LMICs Africa South Asia. A total 36,285 neonates were enrolled BARNARDS study November 2015 December 2017, whom 2,483 diagnosed with culture-confirmed sepsis. Klebsiella pneumoniae (n = 258) main sepsis, Serratia marcescens 151), michiganensis 117), Escherichia coli 75) Enterobacter cloacae complex 57) also detected. We present whole-genome sequencing, susceptibility clinical data 916 out 1,038 isolates (97 not recovered initial isolation at local sites). Enterobacterales (K. pneumoniae, E. cloacae) harboured multiple cephalosporin carbapenem genes. All isolated pathogens resistant antibiotic classes, including those used treat Intraspecies diversity K. indicated antibiotic-resistant lineages Our results will underpin research towards better LMICs.

Language: Английский

Citations

270

Population genomics of hypervirulent Klebsiella pneumoniae clonal-group 23 reveals early emergence and rapid global dissemination DOI Creative Commons
Margaret M. C. Lam, Kelly L. Wyres, Sebastián Duchêne

et al.

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: July 9, 2018

Severe liver abscess infections caused by hypervirulent clonal-group CG23 Klebsiella pneumoniae have been increasingly reported since the mid-1980s. Strains typically possess several virulence factors including an integrative, conjugative element ICEKp encoding siderophore yersiniabactin and genotoxin colibactin. Here we investigate CG23's evolutionary history, showing deep-branching sublineages associated with distinct acquisitions. Over 80% of isolates belong to sublineage CG23-I, which emerged in ~1928 following acquisition ICEKp10 (encoding colibactin), then disseminated globally within human population. CG23-I's distinguishing feature is colibactin synthesis locus, reportedly promotes gut colonisation metastatic infection murine models. These data show circulation K. decades before epidemic was first recognised, provide a framework for future epidemiological experimental studies pneumoniae. To support such present open access, completely sequenced CG23-I isolate, SGH10.

Language: Английский

Citations

257

Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia DOI Creative Commons
Kelly L. Wyres,

To Nguyen Thi Nguyen,

Margaret M. C. Lam

et al.

Genome Medicine, Journal Year: 2020, Volume and Issue: 12(1)

Published: Jan. 16, 2020

Klebsiella pneumoniae is a leading cause of bloodstream infection (BSI). Strains producing extended-spectrum beta-lactamases (ESBLs) or carbapenemases are considered global priority pathogens for which new treatment and prevention strategies urgently required, due to severely limited therapeutic options. South Southeast Asia major hubs antimicrobial-resistant (AMR) K. also the characteristically antimicrobial-sensitive, community-acquired "hypervirulent" strains. The emergence hypervirulent AMR strains lack data on exopolysaccharide diversity pose challenge BSI control worldwide.

Language: Английский

Citations

246

Adaptive evolution of virulence and persistence in carbapenem-resistant Klebsiella pneumoniae DOI
Christoph M. Ernst, Julian R. Braxton, Carlos A. Rodríguez-Osorio

et al.

Nature Medicine, Journal Year: 2020, Volume and Issue: 26(5), P. 705 - 711

Published: April 13, 2020

Language: Английский

Citations

214