Population genomics of Klebsiella pneumoniae

Nature Reviews Microbiology, Год журнала: 2020, Номер 18(6), С. 344 - 359

Опубликована: Фев. 13, 2020

Язык: Английский

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A genomic surveillance framework and genotyping tool for Klebsiella pneumoniae and its related species complex

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Июль 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.

Язык: Английский

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Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia

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

Опубликована: Янв. 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.

Язык: Английский

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Pathogenesis of Gram-Negative Bacteremia

Clinical Microbiology Reviews, Год журнала: 2021, Номер 34(2)

Опубликована: Март 16, 2021

Gram-negative bacteremia is a devastating public health threat, with high mortality in vulnerable populations and significant costs to the global economy. Concerningly, rates of both antimicrobial resistance causative species are increasing. develops three phases. First, bacteria invade or colonize initial sites infection. Second, overcome host barriers, such as immune responses, disseminate from body bloodstream. Third, adapt survive blood blood-filtering organs. To develop new therapies, it critical define species-specific multispecies fitness factors required for model systems that relevant human A small subset responsible majority cases, including

Язык: Английский

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Klebsiella species: Taxonomy, hypervirulence and multidrug resistance

EBioMedicine, Год журнала: 2022, Номер 79, С. 103998 - 103998

Опубликована: Апрель 8, 2022

Members of the genus Klebsiella have rapidly evolved within past decade, generating organisms that simultaneously exhibit both multidrug resistance and hypervirulence (MDR-hv) phenotypes; such are associated with severe hospital- community-acquired infections. Carbapenem-resistant infections unknown optimal treatment regime were particular concern among MDR-hv strains. Recent studies revealed molecular features mobile elements they harbour, allowing identification genetic loci responsible for transmission, stable inheritance, expression or virulence-encoding confer new phenotypic characteristics spp. Here, we provide a comprehensive review on taxonomic position, species composition different phylotypes spp., describing diversity worldwide distribution clones, mutation horizontal gene transfer events drive evolution potential impact human health.

Язык: Английский

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Kaptive 2.0: updated capsule and lipopolysaccharide locus typing for the Klebsiella pneumoniae species complex

Microbial Genomics, Год журнала: 2022, Номер 8(3)

Опубликована: Март 1, 2022

The outer polysaccharide capsule and lipopolysaccharide (LPS) antigens are key targets for novel control strategies targeting Klebsiella pneumoniae related taxa from the K. species complex (KpSC), including vaccines, phage monoclonal antibody therapies. Given importance growing interest in these highly diverse surface antigens, we had previously developed Kaptive, a tool rapidly identifying typing (K) LPS (O) loci whole genome sequence data. Here, report two significant updates, now freely available Kaptive 2.0 ( https://github.com/katholt/kaptive ): (i) addition of 16 K locus sequences to reference database following an extensive search >17 000 KpSC genomes; (ii) enhanced O enable prediction clinically relevant O2 antigen (sub)types, which genetic determinants have been recently described. We applied curated dataset >12 public genomes explore first time, best our knowledge, distribution predicted (sub)types across species, sampling niches clones, highlighted differences distributions that warrant further investigation. As uptake genomic surveillance approaches continues expand globally, application will generate insights essential design effective strategies.

Язык: Английский

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Typing methods based on whole genome sequencing data

One Health Outlook, Год журнала: 2020, Номер 2(1)

Опубликована: Фев. 18, 2020

Abstract Whole genome sequencing (WGS) of foodborne pathogens has become an effective method for investigating the information contained in sequence bacterial pathogens. In addition, its highly discriminative power enables comparison genetic relatedness between bacteria even on a sub-species level. For this reason, WGS is being implemented worldwide and across sectors (human, veterinary, food, environment) investigation disease outbreaks, source attribution, improved risk characterization models. order to extract relevant from large quantity complex data produced by WGS, host bioinformatics tools been developed, allowing users analyze interpret data, starting simple gene-searches phylogenetic studies. Depending research question, complexity dataset their skill set, can choose great variety analysis data. review, we describe approaches phylogenomic studies outbreak give overview selected based Despite efforts last years, harmonization standardization typing are still urgently needed allow easy laboratories, moving towards one health surveillance system

Язык: Английский

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Carbapenem-Resistant Klebsiella pneumoniae: Virulence Factors, Molecular Epidemiology and Latest Updates in Treatment Options

Antibiotics, Год журнала: 2023, Номер 12(2), С. 234 - 234

Опубликована: Янв. 21, 2023

Klebsiella pneumoniae is a Gram-negative opportunistic pathogen responsible for variety of community and hospital infections. Infections caused by carbapenem-resistant K. (CRKP) constitute major threat public health are strongly associated with high rates mortality, especially in immunocompromised critically ill patients. Adhesive fimbriae, capsule, lipopolysaccharide (LPS), siderophores or iron carriers the main virulence factors which contribute to pathogenicity pneumoniae. Colistin tigecycline some last resorts treatment CRKP Carbapenemase production, carbapenemase (KPC) metallo-β-lactamase (MBL), constitutes basic molecular mechanism emergence. Knowledge appearance crucial, as it can determine selection most suitable antimicrobial agent among those recently launched. Plazomicin, eravacycline, cefiderocol, temocillin, ceftolozane–tazobactam, imipenem–cilastatin/relebactam, meropenem–vaborbactam, ceftazidime–avibactam aztreonam–avibactam potent alternatives treating The aim current review highlight pathogenesis provide recent updates on epidemiology options.

Язык: Английский

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Vaccine value profile for Klebsiella pneumoniae

Vaccine, Год журнала: 2024, Номер 42(19), С. S125 - S141

Опубликована: Март 19, 2024

Klebsiella pneumoniae causes community- and healthcare-associated infections in children adults. Globally 2019, an estimated 1.27 million (95% Uncertainty Interval [UI]: 0.91-1.71) 4.95 UI: 3.62-6.57) deaths were attributed to associated with bacterial antimicrobial resistance (AMR), respectively. K. was the second leading pathogen AMR resistant bacteria. Furthermore, rise of both hospital-acquired is a concern for neonates infants who are at high risk invasive disease. There limited antibiotic pipeline new antibiotics treat multidrug infections, vaccines targeted against considered be priority by World Health Organization. Vaccination pregnant women could reduce K.pneumoniae disease their young offspring. In addition, vulnerable children, adolescents adult populations underlying diseases such as immunosuppression from hematologic malignancy, chemotherapy, patients undergoing abdominal and/or urinary surgical procedures, or prolonged intensive care management also potential target groups vaccine. A 'Vaccine Value Profile' (VVP) K.pneumoniae, which contemplates vaccination protect babies birth through least three months age other high-risk populations, provides high-level, holistic assessment available information inform public health, economic societal value preventatives therapeutics. This VVP developed working group subject matter experts academia, non-profit organizations, public-private partnerships, multi-lateral collaboration stakeholders WHO. All contributors have extensive expertise on various elements collectively aimed identify current research knowledge gaps. The using only existing publicly information.

Язык: Английский

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Global emergence of Carbapenem-resistant Hypervirulent Klebsiella pneumoniae driven by an IncFIIK34 KPC-2 plasmid

EBioMedicine, Год журнала: 2025, Номер 113, С. 105627 - 105627

Опубликована: Март 1, 2025

SummaryBackgroundCarbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) has been increasingly reported worldwide, posing a severe challenge to public health; however, the mechanisms driving its emergence and global dissemination remain unclear.MethodsWe analysed CR-hvKp strains derived from canonical hvKp backgrounds, acquired carbapenemase-encoding gene. These were identified 485 CRKp isolates in CRACKLE-2 China cohort, 259 multi-centre study, 67,631 K. genomes available GenBank. Clinical harbouring IncFIIK34 KPC-2 plasmid selected for genome sequencing, RNA-Seq, conjugation assays, vivo, ex vitro phenotypic characterisation.FindingsAnalysis of clinical 414 24 countries GenBank an as prevalent KPC (detected 25%, 45/178 KPC-producing CR-hvKp). Compared with epidemic IncFIIK2 plasmid, exhibited 100- 1000-fold increase frequency (10−4–10−5 vs. 10−7) growth advantage under meropenem challenge–likely due overexpression conjugation-related genes increased blaKPC copy number expression. transconjugants carrying this often reduced mucoviscosity, while retaining hypervirulence both murine models human neutrophil assays.InterpretationThe may be key factor CR-hvKp, underscoring urgent need enhanced molecular surveillance emerging pathogen.FundingNational Natural Science Foundation National Institutes Health.

Язык: Английский

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