Clinical evolution of ST11 carbapenem resistant and hypervirulent Klebsiella pneumoniae.
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ABSTRACT:
SUBMITTER: Xie M
PROVIDER: S-EPMC8169677 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) has recently aroused increasing attention, especially ST11, the predominant CRKP clone in China. Here, we report a case of hv-CRKP-associated infection and reveal the in-host evolution of its mechanism of resistance to tigecycline and polymyxin under clinical therapy. A total of 11 K. pneumoniae carbapenemase (KPC)-producing CRKP strains were consecutively isolated from a male patient who suffered from continuous and multisite infections. String and antimicrobial susceptibility tests identified seven hypermucoviscous strains and three tigecycline-resistant and four colistin-resistant strains. Galleria mellonella larvae infection model confirmed the hypervirulence. Pulsed-field gel electrophoresis (PFGE) separated three PFGE clusters among all strains, and further Southern blotting detected that blaKPC-2 was located on the same-sized plasmid. Whole-genome sequencing showed that all strains belonged to the hv-CRKP ST11-KL64 clone. Diverse hypervirulence factors and resistance genes were identified. Further sequencing with the Nanopore platform was performed on the CRKP-Urine1 strain, which contained one virulence plasmid (pVi-CRKP-Urine1) and two resistance plasmids (pKPC-CRKP-Urine1 and pqnrS1-CRKP-Urine1). The gene mutations responsible for tigecycline or colistin resistance were then amplified with PCR followed by sequencing, which indicated that mutations of ramR and lon were the potential loci for tigecycline resistance and that the pmrB, phoQ and mgrB genes for colistin resistance. A novel frameshift mutation of lon was identified in the high-level tigecycline-resistant strain (MIC, 128 mg/L). The results indicate that the hypervirulent ST11-KL64 clone is a potential threat to antiinfection treatment and is capable of rapid and diverse evolution of resistance during tigecycline and polymyxin treatment.
| S-EPMC8205050 | biostudies-literature
Project description:Klebsiella pneumoniae has been the predominant pathogen of liver abscess, but ST11-K47 carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) has rarely been studied as the causative organism. We identified an ST11-K47 CR-hvKP (HvKp-su1) from the drainage fluid of a liver abscess in a Chinese man who was diagnosed with liver abscess combined with diabetes, pneumonia, pleural infection, abdominal abscess, and splenic abscess. HvKp-su1 was non-hypermucoviscous and lacked the magA and rmpA genes and pLVPK plasmid but exhibited high virulence, with a high mortality rate (90%) to wax moth larvae (G. mellonella), similar to the hypervirulent Klebsiella pneumoniae ATCC43816 (91.67%). Whole-genome sequencing and bioinformatics analysis indicated that HvKp-su1 possesses a plasmid similar to a type of pLVPK-like plasmid (JX-CR-hvKP-2-P2), which is an uncommon plasmid in CR-hvKP. HvKp-su1 carried multiple resistance genes, including blaKPC-2. blaTEM-1, blaSHV-55, and blaCTX-M-65; hypervirulence genes such as aerobactin (iutA), salmochelin (iroEN), and yersiniabactin (ybtAEPQSTUX); and the type 3 fimbriae-encoding system (mrkACDF). Moreover, v_5377 and v_5429 (cofT, CFA/III (CS8)) located on plasmid 1 were simultaneously predicted to be virulence genes. After the long-term combination use of antibiotics, the patient successfully recovered. In summary, our study clarified the clinical and molecular characteristics of a rare ST11-K47 CR-hvKP (HvKp-su1), raising great concerns about the emergence of ST11-K47 CR-hvKP with multidrug resistance and hypervirulence, and providing insights into the control and treatment of liver abscess caused by ST11-K47 CR-hvKP.
| S-EPMC9227846 | biostudies-literature
Project description:BackgroundThe purpose of our study is to analyze the microbiological and clinical characteristics of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) that causes nosocomial infection.MethodsWe collected the carbapenem-resistant K. pneumoniae (CRKP) strains that caused nosocomial infection in a hospital in China and collected the relevant clinical data. We characterized these strains for their antimicrobial and virulence-associated phenotype and genotype and analyzed the clonal relatedness. We screened hypervirulent strains and compared them with non-hypervirulent strains.ResultsWe retrospectively analyzed 62 CRKP strains that caused nosocomial infection in a tertiary hospital within 1 year, of which 41 (41/62, 66.1%) CRKP were considered as CR-hvKP. All CR-hvKP strains were multi-drug resistance (MDR) and the vast majority of isolates (39/41, 95.1%) were ST11 KPC-2-producing strains. Two hypermucoviscous isolates and 4 capsular types were found in 41 CR-hvKP. Twenty-nine isolates (29/41, 70.7%) showed hypervirulence in Galleria mellonella infection model. PFGE showed that ST11-KL47 CR-hvKP and ST11-KL64 CR-hvKP exhibited a high degree of clonality, while non-hypervirulent strains were not significant. CR-hvKP had higher positive rates of blaKPC-2 and blaCTX-M-65 and higher levofloxacin resistance (p < 0.001, p = 0.005 and p = 0.046, respectively) when compared to the non-hypervirulent strains. There was no significant difference between the two groups in terms of in-hospital mortality (7/41, 17.1% vs 5/21, 23.8%, p = 0.743).ConclusionOur research finds that ST11 KPC-2-producing CR-hvKP is the main type of CRKP that caused nosocomial infection, and clonal spread has occurred. We provide more information about CR-hvKP in health care.
| S-EPMC9169163 | biostudies-literature
Project description:Sequence type 36 (ST36) Klebsiella pneumoniae is distributed worldwide. We found an ST36 K. pneumoniae clinical isolate that was carbapenem resistant, carried blaKPC-2, had mucoid regulator gene rmpA, and exhibited high virulence. The finding suggests the emergence of carbapenem-resistant hypervirulent K. pneumoniae of ST36, and surveillance of carbapenem-resistant hypervirulent K. pneumoniae is required.
| S-EPMC6021629 | biostudies-literature
Project description:Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP), a type of Klebsiella pneumoniae (KP) that exhibits hypervirulence and carbapenem resistance phenotypes, can cause severe infections, both hospital- and community-acquired infections. CR-hvKP has brought great challenges to global public health and is associated with significant morbidity and mortality. There are many mechanisms responsible for the evolution of the hypervirulence and carbapenem resistance phenotypes, such as the horizontal transfer of the plasmid carrying the carbapenem resistance gene to hypervirulent Klebsiella pneumoniae (hvKP) or carbapenemase-producing Klebsiella pneumoniae (CRKP) acquiring a hypervirulence plasmid carrying a virulence-encoding gene. Notably, KP can evolve into CR-hvKP by acquiring a hybrid plasmid carrying both the carbapenem resistance and hypervirulence genes. In this review, we summarize the evolutionary mechanisms of resistance and plasmid-borne virulence as well as the prevalence of CR-hvKP.
| S-EPMC9524375 | biostudies-literature
Project description:BackgroundCarbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) is gradually becoming the dominant nosocomial pathogens in the healthcare setting.MethodsA retrospective study was conducted on patients with CR-KP from July 2021 to May 2022 in a teaching hospital. We identified bacterial isolates, collected the clinical data, and performed antimicrobial susceptibility testing, hypermucoviscosity string test, antimicrobial and virulence-associated genotype, as well as multi-locus sequence typing. CR-hvKP was defined as the presence of some combination of rmpA and/or rmpA2 with iucA, iroB, or peg-344. SPSS was used for data analysis. Univariate logistic regression analyses were used for risk factor and all statistically significant variables were included in the multivariate model. Statistical significance was taken to be P < 0.05.ResultsA total of 69 non-duplicated CR-KP isolates were collected, 27 of which were CR-hvKP. Out of the 69 CR-KP strains under investigation, they were distributed across 14 distinct sequence types (STs), wherein ST11 exhibited the highest prevalence, constituting 65.2% (45/69) of the overall isolates. The principal carbapenemase genes identified encompassed blakpc-2, blaNDM-1, and blaOXA-48, with blakpc-2 prevailing as the predominant type, accounting for 73.9% (51/69). A total of 69 CR-KP strains showed high resistance to common clinical antibiotics, with the exception of ceftazidime/avibactam. The ST11 (P = 0.040), ST65 (P = 0.030) and blakpc-2 ST11 clones (P = 0.010) were found to be highly related to hvKp. Regarding the host, tracheal intubation (P = 0.008), intracranial infection (P = 0.020) and neutrophil count (P = 0.049) were significantly higher in the patients with CR-hvKP. Multivariate analysis showed tracheal intubation to be an independent risk factor for CR-hvKP infection (P = 0.030, OR = 4.131). According to the clinical data we collected, tracheal intubation was performed mainly in the elderly with severe underlying diseases, which implied that CR-hvKP has become prevalent among elderly patients with comorbidities.ConclusionsThe prevalence of CR-hvKP may be higher than expected in the healthcare setting. CR-hvKP is gradually becoming the dominant nosocomial pathogen, and its prevalence and treatment will be a major challenge. It is essential to enhance clinical awareness and management of CR-hvKP infection.
| S-EPMC10642049 | biostudies-literature
Project description:ObjectiveTo investigate the epidemiology of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-HvKP) and hypervirulent carbapenem-resistant Klebsiella pneumoniae (Hv-CRKP).MethodsTotally 436 K. pneumoniae strains were collected from 7 hospitals in mainland China between 2017.01 and 2018.02. Sequence types, serotypes, antimicrobial-resistance and virulence genes were analyzed. Additionally, string test, capsule stain, Periodic Acid Schiff stain, fitness analysis, quantitative real-time PCR and mouse lethality test were also performed. Molecular combinations were used to screen putative bla KPC(+)-HvKP and Hv-bla KPC(+)-KP, followed by the confirmation of mouse lethality test.ResultsDiverse detection rates were found for the virulence genes, ranging from c-rmpA (0.0%) to entB (100.0%). According to the molecular criteria, 127, 186, 9 and 26 strains were putatively denoted as HvKP, bla KPC(+)-KP, bla KPC(+)-HvKP and Hv-bla KPC(+)-KP. Mouse lethality test confirmed 2 bla KPC(+)-HvKP strains (JS184 and TZ20) and no Hv-bla KPC(+)-KP. JS184 showed K2 serotype, thin capsule, positive exopolysaccharid and string test. TZ20 presented K20 serotype, thin capsule, negative exopolysaccharide and string test. Compared with the positive control NTUH-K2044, equal galF expression and growth curves were confirmed for JS184 and TZ20.ConclusionsMolecular determination of CR-HvKP and Hv-CRKP brings remarkable bias compared with mouse lethality test. The exact prevalence of CR-HvKP is less than 1.0%, which of Hv-CRKP is much lower.
| S-EPMC9199425 | biostudies-literature
Project description:Background: Multidrug-resistant bacteria, especially those with high virulence, are an emerging problem in clinical settings.Methods: We conducted a multicentre epidemiological and comparative genomic analysis on the evolution, virulence and antimicrobial resistance of carbapenem-resistant Enterobacteriaceae in patients with bacterial liver abscesses from 2012 to 2016.Results: A total of 477 bacterial isolates were collected. Enterobacteriaceae were the main pathogen (89.3%) with K. pneumoniae (52.4%) predominating followed by Escherichia coli (26.8%). All CRKps (3.2%) were of sequence type (ST) 11 and serotypes K47 or K64, and simultaneously possessed acquired blaKPC-2/blaKPC-5 and blaCTX-M-65 together with the multidrug transporter EmrE. Seven Hv-CRKps (five ST11-K47, two ST11-K64) were confirmed by bacteriological test, neutrophil killing assay and Galleria mellonella infection model. Genomic analysis indicated that the emergence of one ST11-K64 Hv-CRKp strain was related to the acquisition of rmpA/rmpA2 genes and siderophore gene clusters, while ST11-K47 Hv-CRKp lacked these traditional virulence genes. Further complete genome analysis of one ST11-K47 Hv-CRKp strain, R16, showed that it acquired a rare plasmid (pR16-Hv-CRKp1) carrying blaKPC-2, blaSHV-12, blaTEM-1, blaCTX-M-65, rmtB and a predicted virulence gene R16_5486 simultaneously.Conclusion: The emergence of the ST11-K47/K64 Hv-CRKps, which are simultaneously multidrug-resistant and hypervirulent, requires urgent control measures to be implemented.
| S-EPMC7034084 | biostudies-literature
Project description:We report an outbreak of carbapenemase-producing hypervirulent Klebsiella pneumoniae in two hospitals that undergo frequent patient transfers. Analysis of 11 completely assembled genomes showed that the bacteria were ST11-K64 strains. Moreover, 12 single nucleotide polymorphisms (SNPs) identified the strains as having originated from the same cluster, and were also indicative of the interhospital transmission of infection. Five plasmids were assembled in each of the strains. One plasmid carried several virulence genes, including the capsular polysaccharide regulators rmpA and rmpA2. Two others carried antimicrobial-resistance genes, including one for carbapenem resistance, bla KPC-2. Comparative genomic analysis indicated the occurrence of frequent and rapid gain and loss of genomic content along transmissions and the co-existence of progeny strains in the same ward. A 10-kbp fragment harboring antimicrobial resistance-conferring genes flanked by insert sequences was missing in a plasmid from strain KP20194c in patient 3, and this strain also likely subsequently infected patient 4. However, strains containing the 10-kbp fragment were also isolated from the ward environment at approximately the same time, and harbored different chromosome indels. Tn1721 and multiple additional insert sequence-mediated transpositions were also seen. These results indicated that there is a rapid reshaping and diversification of the genomic pool of K. pneumoniae facilitated by mobile genetic elements, even a short time after outbreak onset. ST11-K64 CR-hvKP strains have the potential to become new significant superbugs and a threat to public health.
| S-EPMC7688671 | biostudies-literature
Project description:Klebsiella pneumoniae (K. pneumoniae) is one of the most common causes of bacterial meningitis worldwide. The purpose of this study was to investigate the clinical and microbiological characteristics of K. pneumoniae meningitis, as well as the association of antimicrobial resistance, virulence, and patient prognosis. The clinical data of patients with K. pneumoniae meningitis from 2014 to 2020 in a tertiary teaching hospital were retrospectively evaluated. Antimicrobial susceptibility profiles were performed by the agar dilution method and broth microdilution method. The isolates were detected for virulence-related genes, resistance genes, capsular serotypes, and molecular subtypes. A total of 36 individuals with K. pneumoniae meningitis were included in the study, accounting for 11.3% (36/318) of all cases of bacterial meningitis. Of the 36 available isolates, K1, K47, and K64 were tied for the most frequent serotype (7/36, 19.4%). MLST analysis classified the isolates into 14 distinct STs, with ST11 being the most common (14/36, 38.9%). Carbapenem resistance was found in 44.4% (16/36) of the isolates, while hypervirulent K. pneumoniae (HvKP) was found in 66.7% (24/36) of the isolates. The isolates of hypervirulent carbapenem-resistant K. pneumoniae (Hv-CRKP) were then confirmed to be 36.1% (13/36). Importantly, individuals with meningitis caused by Hv-CRKP had a statistically significant higher mortality than the other patients (92.3%, 12/13 vs. 56.5%, 13/23; P < 0.05). The high percentage and fatality of K. pneumoniae-caused meningitis, particularly in Hv-CRKP strains, should be of significant concern. More effective surveillance and treatment solutions will be required in future to avoid the spread of these life-threatening infections over the world.
| S-EPMC9621088 | biostudies-literature