Emergence of two novel tmexCD-toprJ subtypes mediating tigecycline resistance in the megaplasmids from Pseudomonas putida

Microbiological Research, Journal Year: 2025, Volume and Issue: 292, P. 128051 - 128051

Published: Jan. 6, 2025

Language: Английский

---

Adaptive attenuation of virulence mediated by Wzc mutation in ST11-KL47 Carbapenem-resistant Klebsiella pneumonia

Frontiers in Cellular and Infection Microbiology, Journal Year: 2025, Volume and Issue: 15

Published: March 11, 2025

Introduction The impact of the hypermucoviscosity (HMV) phenotype in ST11-KL47 carbapenem-resistant Klebsiella pneumoniae (CRKp) pathogenicity warrants investigation for public health risk assessment. Methods We analyzed 230 clinical CRKp to identify key factor mucoviscosity acquisition via comparative genomic analysis. Sedimentation value served as objective index quantify HMV. virulence vivo was assessed using Galleria mellonella and mouse infection models. employed genome engineering, capsular polysaccharides (CPS) quantification, visualization explore role Wzc mutation CPS biosynthesis biological Wzc-mediated HMV investigated through competitive growth analysis, biofilm formation, serum resistance, anti-phagocytic ability, adhesion assays. Transcriptomic analysis scanning electron microscopy (SEM) were utilized relationship between polysaccharide composition, physical distribution, changes virulence. Results mutations are identified acquisition. Unexpectedly, exhibits reduced versus non-mucoviscosity (NMV) strains different animal models, with disadvantage, decreased adhesion, yet higher ability vitro . extraction genome-engineered verify mediate by standardizing chain length overproducing cell-free extracellular (cell-free EPS). results, lipopolysaccharides (LPS) SEM collectively indicate a downregulation LPS synthesis masking strains. Discussion These findings demonstrate that Wzc-induced attenuates modifying exopolysaccharide composition distribution.

Language: Английский

---

Clonal transmission of a ceftazidime–avibactam-resistant hypervirulent Klebsiella pneumoniae KL64-ST11 strains harboring bla NDM-1 , bla KPC-2 , and ompk36 deletion

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 31, 2025

Ceftazidime–avibactam (CZA) exhibits promising activity against carbapenem-resistant Klebsiella pneumoniae (CRKP). However, CZA-resistant CRKP (CRKP^CZA−R) strains have been emerging. This study explored the mechanism underlying CZA resistance in these strains. CRKP^CZA−R was screened from non-repetitive at our hospital January 1, 2018 to October 30, 2021. The drug and homology were analyzed through carbapenemase phenotype detection next-generation sequencing. In total, 67 of 623 isolates (10.8%) CRKP^CZA−R. most prevalent resistant genes bla_NDM−1 (44.8%, 30/67), followed by bla_IMP−4 (9.0%, 6/67), bla_NDM−5 (7.5%, 5/67), bla_NDM−4 (1.5%, 1/67). Furthermore, 37.3% (25/67) simultaneously harbored more than two carbapenemase-encoding genes. enzyme inhibitor enhancement method detected with high sensitivity (82.1%), particularly for harboring a single (100%). presence or limited its ability. Notably, 21 ST11-KL64 exhibiting bla_NDM−1, bla_KPC−2, also ompk36 deletion, 17 co-carried virulence gene markers, suggesting clonal transmission. Patients infected older serious other drug-resistant strains, which higher MIC₅₀ fosfomycin conclusion, rate relatively high, could be attributed transmission MBL Although can detect carbapenemases specificity, it might ability that produce carbapenemases. both bla_KPC−2 should closely monitored.

Language: Английский

---

KpnK48 clone driving hypervirulent carbapenem-resistant Escherichia coli epidemics: Insights into its evolutionary trajectory similar to Klebsiella pneumoniae

Drug Resistance Updates, Journal Year: 2025, Volume and Issue: unknown, P. 101243 - 101243

Published: April 1, 2025

Language: Английский

---

Unveiling the Clonal Dynamics and transmission mechanism of Carbapenem-Resistant Klebsiella pneumoniae in the ICU environment

International Journal of Antimicrobial Agents, Journal Year: 2025, Volume and Issue: unknown, P. 107532 - 107532

Published: May 1, 2025

Language: Английский

---

Genomic epidemiology of hypervirulent carbapenem-resistant Klebsiella pneumoniae at Jinshan local hospital, Shanghai, during 2014–2018

Journal of Microbiology Immunology and Infection, Journal Year: 2023, Volume and Issue: 57(1), P. 128 - 137

Published: Nov. 3, 2023

Hypervirulent carbapenem-resistant Klebsiella pneumoniae (Hv-CRKP) triggered a significant public health challenge. This study explored the prevalence trends and key genetic characteristics of Hv-CRKP in one Shanghai suburbs hospital during 2014-2018. During five years, strains identified from 2579 CRKP by specific PCR, were subjected to performed short- long-read sequencing technology; epidemiological characteristics, antimicrobial-resistance genes (ARGs), virulence determinants, detailed plasmid profiles conjugation efficiency comprehensively investigated. 155 31 non-Hv-CRKP sequenced. exhibited resistance six common antibiotic classes (>92%). ST11 steadily increased became most prevalent ST (85.2%), followed ST15 (8.5%), ST65 (2.6%), ST23 (1.9%), ST86 (0.6%). ST11-KL64 (65.2%) rapidly 0 2014 93.9% 2018. blaKPC-2 was primary carbapenemase gene (97.4%). Other ARGs switched aac(3)-IId aadA2 aminoglycoside sul1 sul2 sulfanilamide. The time-dated phylogenetic tree divided into four independent evolutionary clades. Clade 1 3 mostly limited ICU, whereas 2 distributed among multiple departments. Compared ybt14 ICEKp12 1, harbored ybt9 ICEKp3 blaCTX-M-65. infected more wards than showed greater transmission capacity. Three plasmids containing crucial demonstrated their early across China. has replaced ST11-KL47 emerged as predominant epidemic subtype various wards, highlighting importance conducting comprehensive surveillance for Hv-CRKP, especially respiratory infections.

Language: Английский

---

Distinct evolution of ST11 KL64 Klebsiella pneumoniae in Taiwan

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: Dec. 8, 2023

Carbapenem-resistant ST11_KL64 Klebsiella pneumoniae emerged as a significant public health concern in Taiwan, peaking between 2013 and 2015, with the majority of isolates exhibiting OXA-48 sole carbapenemase. In this study, we employed whole-genome sequencing to investigate molecular underpinnings collected from 2021. Phylogenomic analysis revealed notable genetic divergence strains Taiwan those China, suggesting an independent evolutionary trajectory. Our findings indicated that ST11_KL64_Taiwan lineage originated Brazil, recombination events leading integration ICEKp11 27-kb fragment at tRNAASN sites, shaping its unique genomic landscape. To further elucidate sublineage, examined plasmid contents. contrast ST11_KL64_Brazil strains, which predominantly carried blaKPC-2, exhibited acquisition epidemic blaOXA-48-carrying IncL plasmid. Additionally, consistently harbored multi-drug resistance IncC plasmid, along collection gene clusters conferred heavy metals phage shock protein system via various Inc-type plasmids. Although few, there were still rare have evolved into hypervirulent CRKP through horizontal pLVPK variants. Comprehensive characterization high-risk not only sheds light on success but also provides essential data for ongoing surveillance efforts aimed tracking spread evolution across different geographical regions. Understanding is crucial developing effective strategies combat emergence dissemination.

Language: Английский

---

Genomic insights and antimicrobial resistance profiles of CRKP and non-CRKP isolates in a Beijing geriatric medical center: emphasizing the blaKPC-2 carrying high-risk clones and their spread

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 13, 2024

Background The escalating resistance of Klebsiella pneumoniae , a prevalent pathogen in healthcare settings, especially its carbapenem-resistant K. (CRKP), to wide array antibiotics, notably β-lactams, constitutes formidable challenge for and global public health management. Methods This research compared the phenotypes genomic profiles CRKP Non-CRKP isolates Beijing hospital, focusing on high-risk bla KPC-2 gene-bearing clones structure mobile genetic elements facilitating their spread across hospital departments. Forty were collected from various departments subjected antimicrobial susceptibility testing whole-genome sequencing analyze features. Results study revealed that among 31 isolates, ST11 is most common sequence type, with K47 OL101 being dominant capsule types, primarily observed respiratory department. In terms susceptibility: 87.5% exhibited multidrug (MDR), high rate 30% against tigecycline. All demonstrated multiple drug classes (≥5 CLSI classes). also showed rates minocycline doxycycline (77.8%). ST11-KL47-OL101 type emerged as predominant clone carrying gene. dominance appears be mediated by pKpnR03_2 plasmid, which harbors not only rmtb but gene clusters pertinent iron transport arsenic resistance. These clustering C3 clade phylogenetic tree, minor variations close evolutionary relationships, suggesting plasmid-driven Conclusion summary, our highlights extensive antibiotic-resistant particular emphasis clonal proliferation strain. finding underscores significant role plasmid-mediated transfer evolution dissemination resistant strains within environments. emphasizes necessity ongoing surveillance antibiotic analysis settings effectively monitor manage these challenges.

Language: Английский

---

Characteristic of KPC-12, a KPC Variant Conferring Resistance to Ceftazidime-Avibactam in the Carbapenem-Resistant Klebsiella pneumoniae ST11-KL47 Clone Background

Infection and Drug Resistance, Journal Year: 2024, Volume and Issue: Volume 17, P. 2541 - 2554

Published: June 1, 2024

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a great threat to public health worldwide. Ceftazidime-avibactam (CZA) is an effective β -lactam/ -lactamase inhibitors against CRKP. However, reports of resistance CZA, mainly caused by carbapenemase (KPC) variants, have increased in recent years. In this study, we aimed describe the characteristics KPC-12, novel KPC variant identified from CZA resistant K. . Methods: The YFKP-97 collected patient with respiratory tract infection was performed whole-genome sequencing (WGS) on Illumina NovaSeq 6000 platform. Genomic were analyzed using bioinformatics methods. Antimicrobial susceptibility testing conducted broth microdilution method. Induction strain carried out vitro as previously described. G. mellonella killing assay used evaluate pathogenicity strains, and conjugation experiment plasmid transfer ability. Results: Strain multidrug-resistant clinical ST11-KL47 confers high-level (16/4 μg/mL). WGS revealed that variant, IncFII (pHN7A8) plasmids (pYFKP-97_a pYFKP-97_b) showed significantly decreased activity carbapenems. addition, there dose-dependent effect bla KPC-12 its ceftazidime. inducible results demonstrated more likely confer than KPC-2 KPC-3 variants. Discussion: Our study patients who not treated also possible be infected CZA-resistant strains harbored variant. Given transformant carrying exhibit CZA-resistance phenotype. Therefore, it important accurately identify variants early possible. Keywords: carbapenem-resistant Enterobacterales , ceftazidime-avibactam,

Language: Английский

---

Molecular characteristics and pathogenic mechanisms of KPC-3 producing hypervirulent carbapenem-resistant Klebsiella pneumoniae (ST23-K1)

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Aug. 15, 2024

Objective This study aimed to comprehensively investigate hypervirulent carbapenem-resistant Klebsiella pneumoniae (CR-hvKP) in the Ningbo region. Importantly, we sought elucidate its molecular characteristics and pathogenic mechanisms. information will provide evidence-based insights for preventing controlling nosocomial infections facilitate improved clinical diagnosis treatment this Methods 96 strains were collected from region between January 2021 December 2022. Whole genome sequencing bioinformatic methods employed identify characterize CR-hvKP at level. The minimum inhibitory concentrations (MICs) of common antibiotics determined using VITEK-2 Compact automatic microbiological analyzer. Plasmid conjugation experiments evaluated transferability resistance plasmids. Finally, mouse virulence assays conducted explore Results Among strains, a single strain, designated CR-hvKP57, was identified, with an isolation frequency 1.04%. Whole-genome revealed strain be ST23 serotype K1 capsule. harbored three 1, pLVPK-like plasmid, carried multiple genes, including rmpA , rmpA2 iroB iucA terB . 2 contained transposable element sequences such as IS15 IS26. 3, classified bla KPC-3 carbapenem gene. Mouse demonstrated high mortality rate associated CR-hvKP57 infection. Additionally, there significant increase IL-1β, IL-6, TNF-α levels response infection, indicating varying degrees inflammatory response. Western blot further suggested that mechanism involves activation NF-κB signaling pathway. Conclusion confirms emergence region, which likely resulted acquisition plasmid by ST23-K1 type Our findings highlight urgent need more judicious use limit resistance. strengthening infection prevention control measures is crucial minimize spread

Language: Английский

---