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

Infection and Immunity, Год журнала: 2021, Номер 89(4)

Опубликована: Фев. 4, 2021

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

Язык: Английский

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Carbapenem-resistant Klebsiella pneumoniae capsular types, antibiotic resistance and virulence factors in China: a longitudinal, multi-centre study

Nature Microbiology, Год журнала: 2024, Номер 9(3), С. 814 - 829

Опубликована: Фев. 29, 2024

Abstract Epidemiological knowledge of circulating carbapenem-resistant Klebsiella pneumoniae (CRKP) is needed to develop effective strategies against this public health threat. Here we present a longitudinal analysis 1,017 CRKP isolates recovered from patients 40 hospitals across China between 2016 and 2020. Virulence gene capsule typing revealed expansion type KL64 (59.5%) alongside decreases in KL47 prevalence. Hypervirulent increased prevalence 28.2% 45.7% Phylogenetic spatiotemporal Beijing Shanghai as transmission hubs accounting for differential geographical strains China. Moderate frequency or O-antigen loss was also detected among isolates. Non-capsular were more susceptible phagocytosis, attenuated during mouse infections, but showed serum resistance biofilm formation. These findings give insight into serotype dynamics, revealing the importance monitoring shifts future development immunological infections.

Язык: Английский

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International and regional spread of carbapenem-resistant Klebsiella pneumoniae in Europe

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июнь 14, 2024

Abstract Carbapenem-resistant Klebsiella pneumoniae (CRKP) are of particular concern due to the spread antibiotic resistance genes associated with mobile genetic elements. In this study, we collected 687 carbapenem-resistant strains recovered among clinical samples from 41 hospitals in nine Southern European countries (2016-2018). We identified 11 major clonal lineages, most isolates belonging high-risk clones ST258/512, ST101, ST11, and ST307. bla KPC-like was prevalent carbapenemase-encoding gene (46%), OXA-48 present 39% isolates. Through combination comparison EURECA collection previous EuSCAPE (2013-2014), investigated circulating Europe exhibiting regional differences. particularly found ST258/512 Greece, Italy, Spain, ST101 Serbia Romania, NDM ST11 OXA-48-like ST14 Türkiye. Genomic surveillance across thus provides crucial insights for local risk mapping informs necessary adaptions implementation control strategies.

Язык: Английский

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Carbapenem-resistant Klebsiella pneumoniae : the role of plasmids in emergence, dissemination, and evolution of a major clinical challenge

Expert Review of Anti-infective Therapy, Год журнала: 2024, Номер 22(1-3), С. 25 - 43

Опубликована: Янв. 18, 2024

Introduction Klebsiella pneumoniae is a major agent of healthcare-associated infections and cause some community-acquired infections, including severe bacteremic associated with metastatic abscesses in liver other organs. Clinical relevance compounded by its outstanding propensity to evolve antibiotic resistance. In particular, the emergence dissemination carbapenem resistance K. has posed challenge due few residual treatment options, which have only recently been expanded new agents. The epidemiological success carbapenem-resistant (CR-Kp) mainly linked clonal lineages that produce carbapenem-hydrolyzing enzymes (carbapenemases) encoded plasmids.

Язык: Английский

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The pivotal role of IncFIB(Mar) plasmid in the emergence and spread of hypervirulent carbapenem-resistant Klebsiella pneumoniae

Science Advances, Год журнала: 2025, Номер 11(5)

Опубликована: Янв. 31, 2025

The hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) poses a substantial challenge to the global health care. However, mechanism behind its evolution and transmission remain elusive. Here, four virulence plasmid types were identified from 310 hv-CRKP isolates collected nationwide during 2017–2018, based on their aerobactin ( iuc locus) lineage IncFIB replicons. Notably, pIUC1-IncFIB(K) 37 pIUC1-IncFIB(Mar), representing two epidemic plasmids in Asia Europe, respectively, accounted for >90% of episodes. Analysis 494 K. (376 2010–2013; 118 2017–2018) 2578 public genomes indicated notable role IncFIB(Mar) emergence spread. Conjugation assays showed helper could efficiently transfer into strain uniquely retromobilize with back CRKP. Thereafter, either lost rapidly or recombined , generating hybrid pIUC1-IncFIB(Mar) plasmid. Our findings elucidated formation, evolution, dissemination trajectories major strains different regions.

Язык: Английский

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A Klebsiella pneumoniae ST307 outbreak clone from Germany demonstrates features of extensive drug resistance, hypermucoviscosity, and enhanced iron acquisition

Genome Medicine, Год журнала: 2020, Номер 12(1)

Опубликована: Дек. 1, 2020

Abstract Background Antibiotic-resistant Klebsiella pneumoniae are a major cause of hospital- and community-acquired infections, including sepsis, liver abscess, pneumonia, driven mainly by the emergence successful high-risk clonal lineages. The K. sequence type (ST) 307 lineage has appeared in several different parts world after first being described Europe 2008. From June to October 2019, we recorded an outbreak extensively drug-resistant ST307 four medical facilities north-eastern Germany. Methods Here, investigated these isolates those from subsequent cases same facilities. We performed whole-genome sequencing study phylogenetics, microevolution, plasmid transmission, as well phenotypic experiments growth curves, hypermucoviscosity, siderophore secretion, biofilm formation, desiccation resilience, serum survival, heavy metal resistance for in-depth characterization this clone. Results Phylogenetics suggest homogenous phylogram with sub-clades containing either only one patient or originating patients, suggesting inter-patient transmission. identified three large plasmids, carrying NDM-1, CTX-M-15, OXA-48, which likely donated other STs even bacterial species (e.g., Enterobacter cloacae ) within clinical settings. Several chromosomally plasmid-encoded, hypervirulence-associated virulence factors yersiniabactin, metabolite transporter, aerobactin, genes) were addition. While growth, comparable control strains, results secretion hypermucoviscosity revealed superiority clone, similar archetypical, hypervirulent strain (hvKP1). Conclusions combination extensive drug virulence, partly conferred through “mosaic” both antibiotic features, demonstrates serious public health implications.

Язык: Английский

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Mobilization of the nonconjugative virulence plasmid from hypervirulent Klebsiella pneumoniae

Genome Medicine, Год журнала: 2021, Номер 13(1)

Опубликована: Июль 22, 2021

Abstract Background Klebsiella pneumoniae , as a global priority pathogen, is well known for its capability of acquiring mobile genetic elements that carry resistance and/or virulence genes. Its plasmid, previously deemed nonconjugative and restricted within hypervirulent K. (hvKP), has disseminated into classic (cKP), particularly carbapenem-resistant (CRKP), which poses alarming challenges to public health. However, the mechanism underlying transfer from hvKP CRKP unclear. Methods A total 28 sequence type (ST) 11 bloodstream infection-causing strains were collected Ruijin Hospital in Shanghai, China, used recipients conjugation assays. Transconjugants obtained assays confirmed by Xba I S1 nuclease pulsed-field gel electrophoresis, PCR detection whole-genome sequencing. The plasmid stability transconjugants was evaluated serial culture. Genetically modified constructed mimic plasmids employed investigate mechanisms mobilization. level extracellular polysaccharides measured mucoviscosity uronic acid quantification. An silico analysis 2608 derived 814 completely sequenced available GenBank performed distribution putative helper mobilizable plasmids. Results mobilized conjugative belonging incompatibility group F (IncF) strain ST11 under low polysaccharide-producing conditions or employing intermediate E. coli strains. via four modes: alone, cotransfer with IncF hybrid formation due two rounds single-strand exchanges at specific 28-bp fusion sites homologous recombination. According analysis, 31.8% (242) 98.8% (84/85) site. All origin Conclusions putatively intermediates help Our findings emphasize importance raising awareness rapid dissemination consistent emergence (hv-CRKP)

Язык: Английский

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Resistome and virulome accretion in an NDM-1-producing ST147 sublineage of Klebsiella pneumoniae associated with an outbreak in Tuscany, Italy: a genotypic and phenotypic characterisation

The Lancet Microbe, Год журнала: 2022, Номер 3(3), С. e224 - e234

Опубликована: Фев. 5, 2022

Язык: Английский

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Genomic surveillance for multidrug-resistant or hypervirulent Klebsiella pneumoniae among United States bloodstream isolates

BMC Infectious Diseases, Год журнала: 2022, Номер 22(1)

Опубликована: Июль 7, 2022

Klebsiella pneumoniae strains have been divided into two major categories: classical K. pneumoniae, which are frequently multidrug-resistant and cause hospital-acquired infections in patients with impaired defenses, hypervirulent severe community-acquired disseminated normal hosts. Both types of may lead to bacteremia associated significant morbidity mortality. The relative burden these among bloodstream isolates within the United States is not well understood.

Язык: Английский

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ESBL plasmids in Klebsiella pneumoniae: diversity, transmission and contribution to infection burden in the hospital setting

Genome Medicine, Год журнала: 2022, Номер 14(1)

Опубликована: Авг. 23, 2022

Abstract Background Resistance to third-generation cephalosporins, often mediated by extended-spectrum beta-lactamases (ESBLs), is a considerable issue in hospital-associated infections as few drugs remain for treatment. ESBL genes are located on large plasmids that transfer horizontally between strains and species of Enterobacteriaceae frequently confer resistance additional drug classes. Whilst plasmid transmission recognised occur the hospital setting, frequency impact infection burden, compared + strain transmission, not well understood. Methods We sequenced genomes clinical carriage isolates Klebsiella pneumoniae complex from year-long surveillance study investigate burden an Australian hospital. Long-term persistence key transmitted was investigated via sequencing ceftriaxone-resistant during 4 years follow-up, beginning 3 after initial study. Results found 25 distinct plasmids. identified one plasmid, which we called Plasmid A, carried bla CTX-M-15 IncF backbone similar pKPN-307. A at least four times into different species/lineages responsible half all episodes 1-year period. Three A-positive persisted locally 3–6 later, detected two backgrounds. Overall accounted 21% follow-up Conclusions Here, systematically surveyed over 1 year single network. events were rare this they had significant sustained multidrug-resistant infections. If onward A-carrying could have been prevented, may reduced number opportunities transmit create novel strains, reducing overall burden.

Язык: Английский

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