Genomic dissection of Klebsiella pneumoniae infections in hospital patients reveals insights into an opportunistic pathogen

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Май 31, 2022

Abstract Klebsiella pneumoniae is a major cause of opportunistic healthcare-associated infections, which are increasingly complicated by the presence extended-spectrum beta-lactamases (ESBLs) and carbapenem resistance. We conducted year-long prospective surveillance study K. clinical isolates in hospital patients. Whole-genome sequence (WGS) data reveals diverse pathogen population, including other species within complex (18%). Several infections were caused variicola/K. hybrids, one shows evidence nosocomial transmission. A wide range antimicrobial resistance (AMR) phenotypes observed, genetic mechanisms identified (mainly plasmid-borne genes). ESBLs correlated with acquired AMR genes (median n = 10). Bacterial genomic features associated onset (OR 2.34, p 0.015) rhamnose-positive capsules 3.12, < 0.001). Virulence plasmid-encoded (aerobactin, hypermucoidy) observed at low-prevalence (<3%), mostly community-onset cases. WGS-confirmed transmission implicated just 10% cases, but strongly 21, 1 × 10 −11 ). estimate 28% risk onward for ESBL-positive strains vs 1.7% ESBL-negative strains. These indicate that hospitalised patients due largely to strains, an additional burden from nosocomially-transmitted community-acquired hypervirulent

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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Genetic determinants of host tropism in Klebsiella phages

Cell Reports, Год журнала: 2023, Номер 42(2), С. 112048 - 112048

Опубликована: Фев. 1, 2023

Bacteriophages play key roles in bacterial ecology and evolution are potential antimicrobials. However, the determinants of phage-host specificity remain elusive. Here, we isolate 46 phages to challenge 138 representative clinical isolates Klebsiella pneumoniae, a widespread opportunistic pathogen. Spot tests show narrow host range for most phages, with <2% 6,319 combinations tested yielding detectable interactions. Bacterial capsule diversity is main factor restricting phage range. Consequently, phage-encoded depolymerases tropism, depolymerase sequence types associated ability infect specific capsular across families. all broader found do not encode canonical depolymerases, suggesting alternative modes entry. These findings expand our knowledge complex interactions between bacteria their viruses point out feasibility predicting first steps infection using genome sequences.

Язык: Английский

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Expansion and transmission dynamics of high risk carbapenem-resistant Klebsiella pneumoniae subclones in China: An epidemiological, spatial, genomic analysis

Drug Resistance Updates, Год журнала: 2024, Номер 74, С. 101083 - 101083

Опубликована: Март 29, 2024

Carbapenem-resistant Klebsiella pneumonia (CRKP) is a global threat that varies by region. The distribution, evolution, and clinical implications of the ST11 CRKP clone remain obscure. We conducted multicenter molecular epidemiological survey using isolates obtained from 28 provinces municipalities across China between 2011 2021. integrated sequences public databases performed genetic epidemiology analysis CRKP. Among CRKP, KL64 serotypes exhibited considerable expansion, increasing 1.54% to 46.08% Combining our data with databases, phylogenetic phylogeography analyses indicated appeared in Americas 1996 spread worldwide, key clones progressing China's southeastern coast inland 2010. Global showed has evolved virulent, resistant clade notable regional spread. Single-nucleotide polymorphism (SNP) identified BMPPS (bmr3, mltC, pyrB, ppsC, sdaC) as marker for this clade. SNP associated high mortality strong anti-phagocytic competitive traits vitro. high-risk subclone expansion potential survival advantages, probably owing factors.

Язык: Английский

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Bacterial capsules: Occurrence, mechanism, and function

npj Biofilms and Microbiomes, Год журнала: 2024, Номер 10(1)

Опубликована: Март 13, 2024

Abstract In environments characterized by extended multi-stress conditions, pathogens develop a variety of immune escape mechanisms to enhance their ability infect the host. The capsules, polymers that bacteria secrete near cell wall, participates in numerous bacterial life processes and plays crucial role resisting host attacks adapting niche. Here, we discuss relationship between capsules virulence, summarizing molecular capsular regulation pathogenesis provide new insights into research on pathogenic bacteria.

Язык: Английский

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Prediction of strain level phage–host interactions across the Escherichia genus using only genomic information

Nature Microbiology, Год журнала: 2024, Номер 9(11), С. 2847 - 2861

Опубликована: Окт. 31, 2024

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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An update to the database for Acinetobacter baumannii capsular polysaccharide locus typing extends the extensive and diverse repertoire of genes found at and outside the K locus

Microbial Genomics, Год журнала: 2022, Номер 8(10)

Опубликована: Окт. 10, 2022

Several novel non-antibiotic therapeutics for the critical priority bacterial pathogen, Acinetobacter baumannii , rely on specificity to cell-surface capsular polysaccharide (CPS). Hence, prediction of CPS type deduced from genes in whole genome sequence data underpins development and application these therapies. In this study, we provide a comprehensive update A. K locus reference database typing (available Kaptive v. 2.0.1 ) include 145 new KL, providing total 237 KL sequences. The was also reconfigured compatibility with updated 2.0.0 code that enables ‘K type’ special logic parameters defined by detected combinations additional outside locus. Validation against 8994 publicly available assemblies NCBI databases identified specific 73.45 % genomes perfect, very high or confidence. Poor quality presence insertion sequences were main reasons lower confidence levels. Overall, 17 overrepresented genomes, KL2 most common followed related KL3 KL22. Substantial variation gene content central portion locus, usually includes type, included 34 distinct groups synthesis various complex sugars >400 forming linkages between adding non-sugar substituents. A repertoire 681 types found across 88.4 <5 KL.

Язык: Английский

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Nanopore-only assemblies for genomic surveillance of the global priority drug-resistant pathogen, Klebsiella pneumoniae

Microbial Genomics, Год журнала: 2023, Номер 9(2)

Опубликована: Фев. 8, 2023

Oxford Nanopore Technologies (ONT) sequencing has rich potential for genomic epidemiology and public health investigations of bacterial pathogens, particularly in low-resource settings at the point care, due to its portability affordability. However, low base-call accuracy limited reliability ONT data critical tasks such as antimicrobial resistance (AMR) virulence gene detection typing, serotype prediction, cluster identification. Thus, Illumina remains standard surveillance despite higher capital running costs. We tested ONT-only assemblies common applied genomics (genotyping detection, implemented via Kleborate, Kaptive Pathogenwatch), using from 54 unique Klebsiella pneumoniae isolates. reads generated MinION with R9.4.1 flowcells were basecalled three alternative models [Fast, High-accuracy (HAC) Super-accuracy (SUP), available within ONT's Guppy software], assembled Flye polished Medaka. Accuracy typing was compared that Illumina-only hybrid ONT+Illumina assemblies, constructed same isolates reference standards. The most resource-intensive ONT-assembly approach (SUP basecalling, or without Medaka polishing) performed best, yielding reliable capsule (K) type calls all strains (100 % exact best matching locus), multi-locus sequence (MLST) assignment (98.3 match single-locus variants), good acquired AMR genes mutations (88-100 correct identification across various drug classes). Distance-based trees SUP+Medaka accurately reflected overall genetic relationships between definition outbreak clusters problematic inflation SNP counts by high errors. could be reliably used 'rule out' distinct lineages suspected transmission clusters. HAC basecalling + polishing similarly SUP polishing. Therefore, we recommend investing compute resources into model), wherever time allow, note is also worthwhile improved performance. Overall, our results show MLST, K determinants can identified flowcell data. challenging this technology.

Язык: Английский

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Global, regional, and national estimates of the impact of a maternal Klebsiella pneumoniae vaccine: A Bayesian modeling analysis

PLoS Medicine, Год журнала: 2023, Номер 20(5), С. e1004239 - e1004239

Опубликована: Май 22, 2023

Background Despite significant global progress in reducing neonatal mortality, bacterial sepsis remains a major cause of deaths. Klebsiella pneumoniae ( K . ) is the leading pathogen globally underlying cases and frequently resistant to antibiotic treatment regimens recommended by World Health Organization (WHO), including first-line therapy with ampicillin gentamicin, second-line amikacin ceftazidime, meropenem. Maternal vaccination prevent infection could reduce burden low- middle-income countries (LMICs), but potential impact poorly quantified. We estimated such on deaths project effects routine immunization pregnant women vaccine as antimicrobial resistance (AMR) increases. Methods findings developed Bayesian mixture-modeling framework estimate hypothetical maternal 70% efficacy administered coverage equivalent that tetanus infections mortality. To parameterize our model, we used data from 3 studies and/or mortality—with 2,330 neonates who died surveilled 2016 2020 undertaken 18 mainly LMICs across all WHO regions (Ethiopia, Kenya, Mali, Mozambique, Nigeria, Rwanda, Sierra Leone, South Africa, Uganda, Brazil, Italy, Greece, Pakistan, Bangladesh, India, Thailand, China, Vietnam). Within these studies, 26.95% fatal were culture-positive for analyzed 9,070 genomes human isolates gathered 2001 quantify temporal rate acquisition AMR genes predict future number drug-resistant be averted vaccination. Resistance rates carbapenems are increasing most rapidly 22.43% [95th percentile credible interval (CrI): 5.24 41.42] caused meropenem-resistant Globally, avert 80,258 [CrI: 18,084 189,040] 399,015 334,523 485,442] yearly worldwide, accounting more than 3.40% 0.75 8.01] The largest relative benefits Africa (Sierra Niger) South-East Asia (Bangladesh) where over 6% Nevertheless, modeling only considers country-level trends unable consider within-country variability prevalence may projected sepsis. Conclusions A have widespread, sustained continues increase.

Язык: Английский

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