A Foundation Model Identifies Broad-Spectrum Antimicrobial Peptides against Drug-Resistant Bacterial Infection DOI Creative Commons
Tingting Li,

Xuanbai Ren,

Xiaoli Luo

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 30, 2024

Development of potent and broad-spectrum antimicrobial peptides (AMPs) could help overcome the resistance crisis. We develop a peptide language-based deep generative framework (deepAMP) for identifying potent, AMPs. Using deepAMP to reduce enhance membrane-disrupting abilities AMPs, we identify, synthesize, experimentally test 18 T1-AMP (Tier 1) 11 T2-AMP 2) candidates in two-round design by employing cross-optimization-validation. More than 90% designed AMPs show better inhibition penetratin both Gram-positive (i.e., S. aureus) Gram-negative bacteria K. pneumoniae P. aeruginosa). T2-9 shows strongest antibacterial activity, comparable FDA-approved antibiotics. that three (T1-2, T1-5 T2-10) significantly aureus compared ciprofloxacin are effective against skin wound infection female mouse model infected with aeruginosa. In summary, expedites discovery effective, drug-resistant bacteria.

Language: Английский

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

Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort DOI Open Access
Youwen Qin, Aki S. Havulinna, Yang Liu

et al.

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(2), P. 134 - 142

Published: Feb. 1, 2022

Language: Английский

Citations

317

Emerging Antimicrobial-Resistant High-Risk Klebsiella pneumoniae Clones ST307 and ST147 DOI

Gisele Peirano,

Liang Chen, Barry N. Kreiswirth

et al.

Antimicrobial Agents and Chemotherapy, Journal Year: 2020, Volume and Issue: 64(10)

Published: Aug. 3, 2020

There is an enormous global public health burden due to antimicrobial-resistant (AMR) Klebsiella pneumoniae high-risk clones. K. ST307 and ST147 are recent additions the family of successful clones in species. Both likely emerged Europe during early mid-1990s and, a relatively short time, became prominent pathogens, spreading all continents (with exception Antarctica). consist multiple clades/clusters associated with various carbapenemases (i.e., KPCs, NDMs, OXA-48-like, VIMs). endemic Italy, Colombia, United States (Texas), South Africa, while India, Greece, certain North African countries. have been introduced into regions nonendemicity, leading worldwide nosocomial outbreaks. Genomic studies showed contain identical gyrA parC mutations obtained plasmids blaCTX-M-15 mid-2000s, which aided their distribution. then acquired late 2000s, establishing themselves as important AMR pathogens regions. underreported restricted detection methodologies. ability become major threats distribution, cause serious infections, association AMR, including panresistance. The medical community at large, especially those concerned antimicrobial resistance, should be aware looming threat posed by emerging such ST147.

Language: Английский

Citations

231

Virulence Factors in Hypervirulent Klebsiella pneumoniae DOI Creative Commons
Jie Zhu, Tao Wang, Liang Chen

et al.

Frontiers in Microbiology, Journal Year: 2021, Volume and Issue: 12

Published: April 8, 2021

Hypervirulent Klebsiella pneumoniae (hvKP) has spread globally since first described in the Asian Pacific Rim. It is an invasive variant that differs from classical K. (cKP), with hypermucoviscosity and hypervirulence, causing community-acquired infections, including pyogenic liver abscess, pneumonia, meningitis, endophthalmitis. utilizes a battery of virulence factors for survival pathogenesis, such as capsule, siderophores, lipopolysaccharide, fimbriae, outer membrane proteins, type 6 secretion system, which former two are dominant. This review summarizes these hvKP-associated order to understand its molecular pathogenesis shed light on new strategies improve prevention, diagnosis, treatment hvKP-causing infection.

Language: Английский

Citations

203

A global perspective on the convergence of hypervirulence and carbapenem resistance in Klebsiella pneumoniae DOI Creative Commons
Peng Lan, Yan Jiang, Jiancang Zhou

et al.

Journal of Global Antimicrobial Resistance, Journal Year: 2021, Volume and Issue: 25, P. 26 - 34

Published: March 2, 2021

Hypervirulence and carbapenem resistance have emerged as two distinct evolutionary directions for Klebsiella pneumoniae, which pose a great threat in clinical settings. Multiple virulence factors contribute to hypervirulence, the mechanisms of are complicated. However, more K. pneumoniae strains been identified recent years integrating both phenotypes, resulting devastating outcomes. Hypervirulent carbapenem-resistant (CR-hvKP) early 2010s thereafter become increasingly prevalent. CR-hvKP primarily prevalent Asia, especially China, but reported all over world. Mechanisms emergence can be summarised by three patterns: (i) (CRKP) acquiring hypervirulent phenotype; (ii) (hvKP) (iii) hypervirulence hybrid plasmid. With their global dissemination, continued surveillance should highly prioritised.

Language: Английский

Citations

177

Klebsiella species: Taxonomy, hypervirulence and multidrug resistance DOI Creative Commons
Ning Dong, Xuemei Yang, Edward Wai‐Chi Chan

et al.

EBioMedicine, Journal Year: 2022, Volume and Issue: 79, P. 103998 - 103998

Published: April 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.

Language: Английский

Citations

167

ESKAPE pathogens: antimicrobial resistance, epidemiology, clinical impact and therapeutics DOI
William R. Miller, César A. Arias

Nature Reviews Microbiology, Journal Year: 2024, Volume and Issue: 22(10), P. 598 - 616

Published: June 3, 2024

Language: Английский

Citations

166

Kaptive 2.0: updated capsule and lipopolysaccharide locus typing for the Klebsiella pneumoniae species complex DOI Creative Commons
Margaret M. C. Lam, Ryan R. Wick, Louise M. Judd

et al.

Microbial Genomics, Journal Year: 2022, Volume and Issue: 8(3)

Published: March 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.

Language: Английский

Citations

158

Carbapenem-Resistant Klebsiella pneumoniae: Virulence Factors, Molecular Epidemiology and Latest Updates in Treatment Options DOI Creative Commons
Theodoros Karampatakis, Katerina Tsergouli, Payam Behzadi

et al.

Antibiotics, Journal Year: 2023, Volume and Issue: 12(2), P. 234 - 234

Published: Jan. 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.

Language: Английский

Citations

146

Genomic dissection of Klebsiella pneumoniae infections in hospital patients reveals insights into an opportunistic pathogen DOI Creative Commons
Claire L. Gorrie,

Mirjana Mirčeta,

Ryan R. Wick

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: May 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

Language: Английский

Citations

117