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Phenotypic and genetic characterization of hypervirulent Klebsiella pneumoniae in patients with liver abscess and ventilator-associated pneumonia.

ABSTRACT: Ventilator-associated pneumonia (VAP) and pyogenic liver abscess (PLA) due to Klebsiella pneumoniae infection can trigger life-threatening malignant consequences, however, there are few studies on the strain-associated clinical pathogenic mechanisms between VAP and PLA. A total of 266 patients consist of 129 VAP and 137 PLA were included for analysis in this study. We conducted a comprehensive survey for the two groups of K. pneumoniae isolates, including phenotypic experiments, clinical epidemiology, genomic analysis, and instrumental analysis, i.e., to obtain the genomic differential profile of K. pneumoniae strains responsible for two distinct infection outcomes. We found that PLA group had a propensity for specific underlying diseases, especially diabetes and cholelithiasis. The resistance level of VAP was significantly higher than that of PLA (78.57% vs. 36%, P < 0.001), while the virulence results were opposite. There were also some differences in key signaling pathways of biochemical processes between the two groups. The combination of iucA, rmpA, hypermucoviscous phenotype, and ST23 presented in K. pneumoniae infection is more important and highly prudent for timely treatment. The present study may contribute a benchmark for the K. pneumoniae clinical screening, epidemiological surveillance, and effective therapeutic strategies.

SUBMITTER: Guo M

PROVIDER: S-EPMC10644596 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Phenotypic and genetic characterization of hypervirulent Klebsiella pneumoniae in patients with liver abscess and ventilator-associated pneumonia.

Guo Mingquan M Gao Bo B Su Jun J Zeng Yigang Y Cui Zelin Z Liu Haodong H Guo XiaoKui X Zhu Yongzhang Y Wei Beiwen B Zhao Yanan Y Qin Juanxiu J Lu Xiaoye X Li Qingtian Q

BMC microbiology 20231113 1

Ventilator-associated pneumonia (VAP) and pyogenic liver abscess (PLA) due to Klebsiella pneumoniae infection can trigger life-threatening malignant consequences, however, there are few studies on the strain-associated clinical pathogenic mechanisms between VAP and PLA. A total of 266 patients consist of 129 VAP and 137 PLA were included for analysis in this study. We conducted a comprehensive survey for the two groups of K. pneumoniae isolates, including phenotypic experiments, clinical epidemi ...[more]

PMID: 37957579

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Project description:Cooccurrence of multidrug resistant (MDR) and hypervirulence phenotypes in liver abscess-causing Klebsiella pneumoniae (LAKp) would pose a major threat to public health. However, relatively little information is available on the genomic and phenotypic characteristics of this pathogen. This study aimed to investigate the virulence and resistance phenotype and genotype of MDR LAKp strains from 2016 to 2020. We collected 18 MDR LAKp strains from 395 liver abscess samples and characterized these strains using antimicrobial susceptibility test, string test, mucoviscosity assay, biofilm formation assay, Galleria mellonella killing assay, and whole-genome sequencing. Besides, phylogenetic and comparative genomic analyses were performed on these MDR LAKp, along with 94 LAKp genomes from global sources. Most of these MDR LAKp strains exhibited resistance to cephalosporins, quinolones, and chloramphenicol. Virulence assays revealed that only half of MDR LAKp strains exhibited higher virulence than classical MDR strain K. pneumoniae MGH78578. Importantly, we identified three ST11 KL64 hypervirulence carbapenem-resistant strains carrying blaKPC-2 and one colistin-resistant strain carrying mcr-1. Phylogenetic analysis revealed that 112 LAKp genomes were divided into two clades, and most of MDR LAKp strains in this study belonged to clade 1 (83.33%, 15/18). We also detected the loss of mucoviscosity mediated by mutations and ISKpn14 insertion in rmpA, and the latter representing a novel mechanism by which bacteria regulate RmpA system. This study provides novel insights into MDR LAKp and highlights the necessity for measures to prevent further spread of such organisms in hospital settings and the community. IMPORTANCE Pyogenic liver abscess is a potentially life-threatening suppurative infection of hepatic parenchyma. K. pneumoniae has emerged as a predominant pathogen of pyogenic liver abscess. Liver abscess-causing K. pneumoniae is generally considered hypervirulent K. pneumoniae and is susceptible to most antibiotics. Recently, convergence of multidrug resistant and hypervirulence phenotypes in liver abscess-causing K. pneumoniae was emerging and poses a major threat to public health. However, relatively little information is available on liver abscess-causing multidrug-resistant hypervirulent K. pneumoniae. In this study, we characterized phenotype and genotype of virulence and resistance of 18 multidrug-resistant hypervirulent liver abscess-causing K. pneumoniae strains collected from 395 pyogenic liver abscess cases in a tertiary teaching hospital over a 5-year period to enable in-depth understanding of this pathogen.

Project description:BackgroundThe prevalence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (hv-CRKP) is a serious public threat globally. Here, we performed clinical, molecular, and phenotypic monitoring of hv-CRKP strains isolated from the intensive care unit (ICU) to offer evidence for prevention and control in hospitals.MethodsData analysis of ICU patients suffering from ventilator-associated pneumonia (VAP) because of hv-CRKP infection, admitted at the Chinese Teaching Hospital between March 2019 and September 2021 was performed. Patients' antibiotic-resistance genes, virulence-associated genes, and capsular serotypes of these isolates were detected. Homology analysis of the strains was performed by MLST and PFGE. Six different strains were tested for their virulence traits using the serum killing test and the Galleria mellonella infection assay. For whole genome sequencing, KP3 was selected as a representative strain.ResultsClinical data of 19 hv-CRKP-VAP patients were collected and their hv-CRKP were isolated, including 10 of ST11-KL64, 4 of ST15-KL112, 2 of ST11-KL47, 1 of ST15-KL19, 1 of ST17-KL140, and 1 of ST48-KL62. Four ST15 and 8 ST11 isolates revealed high homology, respectively. Most strains carried the carbapenemase gene blaKPC-2 (14/19, 73.68%), followed by blaOXA-232 (4/19, 21.05%). All strains were resistant to almost all the antibiotics except polymyxin and tigacycline. Ten patients were treated with polymyxin or tigacycline based on their susceptibility results, and unfortunately 6 patients died. All strains exhibited a hyper-viscous phenotype, and the majority (17/19, 89.47%) of them contained rmpA and rmpA2. The serum killing test showed that KP9 was resistant to normal healthy serum, others were intermediately or highly sensitive. G. mellonella larvae infection assay suggested that the strains in this study were hypervirulent.ConclusionThis study highlights the dominant strain and molecular epidemiology of hv-CRKP in a hospital in China. We should pay more attention to the effect of hv-CRKP on VAP, strengthen monitoring and control transmission.

Project description:While Klebsiella pneumoniae is a common cause of nosocomial and community-acquired infections, including pneumonia and pyogenic liver abscess, little is known about the population structure of this bacterium. In this study, we investigated the prevalence and molecular characteristics of K. pneumoniae isolates from carriers, pyogenic liver abscess patients, and pneumonia patients, and genomic and phenotypic assays were used to determine the differences among the isolates. A total of 232 K. pneumoniae isolates were subtyped into 74 sequence types (STs). The isolates from different sources had their own STs, and the predominant subtypes in liver abscess and pneumonia patients were ST23 and ST11, respectively. Pangenome analysis also distinguished three phylogroups that were consistent with the isolate sources. The isolates collected from liver abscess patients carried significantly more virulence factors, and those from pneumonia patients harbored significantly more resistance genes and replicons. Almost all isolate STs (93/97 [95.88%]) from liver abscesses strongly correlated with the virulence factor salmochelin, while most pneumonia isolate STs (52/53 [98.11%]) from pneumonia did not correlate with salmochelin. The isolates collected from liver abscesses showed higher virulence in the cytotoxicity and mouse models. These data provide genomic support for the proposal that isolates collected from carriers, liver abscess patients, and pneumonia patients have distinct genomic features. Isolates from the different sources are largely nonoverlapping, suggesting that different patients may be infected via different sources. Further studies on the pathogenic mechanisms of salmochelin and other virulence factors will be required. IMPORTANCE While Klebsiella pneumoniae is a common cause of nosocomial and community-acquired infections, including pneumonia and pyogenic liver abscess, little is known about the population structure of this bacterium. We collected 232 isolates from carriers, pyogenic liver abscess patients, and pneumonia patients, and the isolates from different sources had their own sequence types. Pangenome analysis also distinguished three phylogroups that were consistent with the isolate sources. The isolates collected from liver abscess patients carried significantly more virulence factors, and those from pneumonia patients harbored significantly more resistance genes and replicons. Besides, there was a strong link between salmochelin and liver abscess. The isolates collected from liver abscesses also showed higher virulence in the cytotoxicity and mouse models. Isolates collected from different sources have distinct genomic features, suggesting that different patients may be infected via different sources.

Dataset Information

Phenotypic and genetic characterization of hypervirulent Klebsiella pneumoniae in patients with liver abscess and ventilator-associated pneumonia.

Publications

Phenotypic and genetic characterization of hypervirulent Klebsiella pneumoniae in patients with liver abscess and ventilator-associated pneumonia.

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