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Comparative analysis of Klebsiella pneumoniae strains isolated in 2012-2016 that differ by antibiotic resistance genes and virulence genes profiles.

ABSTRACT: The antibacterial resistance and virulence genotypes and phenotypes of 148 non-duplicate Klebsiella pneumoniae strains collected from 112 patients in Moscow hospitals in 2012-2016 including isolates from the respiratory system (57%), urine (30%), wounds (5%), cerebrospinal fluid (4%), blood (3%), and rectal swab (1%) were determined. The majority (98%) were multidrug resistant (MDR) strains carrying blaSHV (91%), blaCTX-M (74%), blaTEM (51%), blaOXA (38%), and blaNDM (1%) beta-lactamase genes, class 1 integrons (38%), and the porin protein gene ompK36 (96%). The beta-lactamase genes blaTEM-1, blaSHV-1, blaSHV-11, blaSHV-110, blaSHV-190, blaCTX-M-15, blaCTX-M-3, blaCTX-M-55, blaOXA-48, blaOXA-244, and blaNDM-1 were detected; class 1 integron gene cassette arrays (aadA1), (dfrA7), (dfrA1-orfC), (aadB-aadA1), (dfrA17-aadA5), and (dfrA12-orfF-aadA2) were identified. Twenty-two (15%) of clinical K. pneumoniae strains had hypermucoviscous (HV) phenotype defined as string test positive. The rmpA gene associated with HV phenotype was detected in 24% of strains. The intrapersonal mutation of rmpA gene (deletion of one nucleotide at the polyG tract) was a reason for negative hypermucoviscosity phenotype and low virulence of rmpA-positive K. pneumoniae strain KPB584. Eighteen virulent for mice strains with LD50 ? 104 CFU were attributed to sequence types ST23, ST86, ST218, ST65, ST2174, and ST2280 and to capsular types K1, K2, and K57. This study is the first report about hypervirulent K. pneumoniae strain KPB2580-14 of ST23K1 harboring extended-spectrum beta-lactamase CTX-M-15 and carbapenemase OXA-48 genes located on pCTX-M-15-like and pOXA-48-like plasmids correspondingly.

SUBMITTER: Lev AI

PROVIDER: S-EPMC6056825 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Comparative analysis of Klebsiella pneumoniae strains isolated in 2012-2016 that differ by antibiotic resistance genes and virulence genes profiles.

Lev Anastasia I AI Astashkin Eugeny I EI Kislichkina Angelina A AA Solovieva Ekaterina V EV Kombarova Tatiana I TI Korobova Olga V OV Ershova Olga N ON Alexandrova Irina A IA Malikov Vladimir E VE Bogun Alexander G AG Borzilov Alexander I AI Volozhantsev Nikolay V NV Svetoch Edward A EA Fursova Nadezhda K NK

Pathogens and global health 20180430 3

The antibacterial resistance and virulence genotypes and phenotypes of 148 non-duplicate Klebsiella pneumoniae strains collected from 112 patients in Moscow hospitals in 2012-2016 including isolates from the respiratory system (57%), urine (30%), wounds (5%), cerebrospinal fluid (4%), blood (3%), and rectal swab (1%) were determined. The majority (98%) were multidrug resistant (MDR) strains carrying blaSHV (91%), blaCTX-M (74%), blaTEM (51%), blaOXA (3 ...[more]

PMID: 29708041

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Project description:Introduction:Klebsiella pneumoniae is one of the most important infectious agents in neonates. There are "classic" and hypervirulent strains of K. pneumoniae. The "classic" non-virulent strain of K. pneumoniae, producing extended-spectrum beta-lactamases (ESBLs), is associated with nosocomial infections. Hypervirulent K. pneumoniae strains are associated with invasive infections in previously healthy adult people, and most of them exhibit antimicrobial susceptibility. The role of virulent strains of K. pneumoniae (including hv-KP) in neonatal infections is unknown. The aim of the study was the assessment of the impact of virulence factors and antibiotic resistance of K. pneumoniae strains on clinical features and outcomes of neonatal infection. Materials and Methods: Two groups of infants were enrolled. The first group consisted of 10 neonates with sepsis caused by K. pneumoniae. The second group consisted of 10 neonates with urinary tract infection (UTI) caused by K. pneumoniae. We investigated the susceptibility of K. pneumoniae isolates to antibiotics, the ability of the microorganism to produce ESBL, and virulence factors, including the rmpA gene, aerobactin, and colibactin genes. In neonates with sepsis, we investigated K. pneumoniae isolates, which was taken from the blood, in neonates with UTI-from the urine. Results: In neonates with sepsis testing of K. pneumoniae isolates for ESBL production was positive in 60% of cases, in neonates with UTI-in 40% of cases. All blood and urine ESBL producing K. pneumoniae isolates were resistant to ampicillins, including protected ones, and third-generation cephalosporins. At the same time, these isolates were sensitive to meropenem, amikacin, and ciprofloxacin. The rmpA gene was detected in four blood, and three urine K. pneumoniae isolates. In neonates with sepsis rmpA gene in two cases was detected in ESBL-producing K. pneumoniae isolates. They were infants with meningitis, and both cases were fatal. In the group of infants with UTI, the rmpA gene was detected only in K. pneumoniae isolates not producing ESBL. Aerobactin and colibactin genes were detected in two neonates with sepsis and in three neonates with UTI. In all cases, aerobactin and colibactin genes were detected only in rmpA-positive K. pneumoniae isolates. Out of three fatal outcomes, two cases were caused by hv-KP producing ESBL. Conclusion: The prevalence of virulent strains of K. pneumoniae among neonates with sepsis and other neonatal infection is higher than we think. The most severe forms of neonatal sepsis with an unfavorable outcome in our study were due to virulent strains of K. pneumoniae.

Project description:Global increases in the use of carbapenems have resulted in several strains of Gram-negative bacteria acquiring carbapenem resistance, thereby limiting treatment options. Klebsiella pneumoniae is a common carbapenem-resistant pathogenic bacterium that is widely studied to identify novel antibiotic resistance mechanisms and drug targets. Antibiotic-resistant clinical isolates generally harbor many genetic alterations, and the identification of responsible mutations would provide insights into the molecular mechanisms of antibiotic resistance. We propose a method to prioritize mutated genes responsible for antibiotic resistance on the basis of expression changes in their local subnetworks, hypothesizing that mutated genes that show significant expression changes among the corresponding functionally associated genes are more likely to be involved in the carbapenem resistance. For network-based gene prioritization, we developed KlebNet (www.inetbio.org/klebnet), a genome-scale cofunctional network of K. pneumoniae genes. Using KlebNet, we reconstructed the functional modules for carbapenem resistance and virulence and identified the functional association between antibiotic resistance and virulence. Using complementation assays with the top candidate genes, we were able to validate a novel gene that negatively regulated carbapenem resistance and four novel genes that positively regulated virulence in Galleria mellonella larvae. Therefore, our study demonstrated the feasibility of network-based identification of genes required for antibiotic resistance and virulence of human-pathogenic bacteria.IMPORTANCEKlebsiella pneumoniae is a major bacterial pathogen that causes pneumonia and urinary tract infections in human. K. pneumoniae infections are treated with carbapenem, but carbapenem-resistant K. pneumoniae has been spreading worldwide. We are able to identify antimicrobial-resistant genes among mutated genes of the antibiotic-resistant clinical isolates. However, they usually harbor many mutated genes, including those that cause weak or neutral functional effects. Therefore, we need to prioritize the mutated genes to identify the more likely candidates for the follow-up functional analysis. For this study, we present a functional network of K. pneumoniae genes and propose a network-based method of prioritizing the mutated genes of the resistant clinical isolates. We also reconstructed the network-based functional modules for carbapenem resistance and virulence and retrieved the functional association between antibiotic resistance and virulence. This study demonstrated the feasibility of network-based analysis of clinical genomics data for the study of K. pneumoniae infection.

Project description:Carbapenemase-producing Klebsiella pneumoniae (CP-Kpn) are a major concern for nosocomial infections. We previously reported an intensive care unit (ICU) outbreak of CP-Kpn. This study investigated the transmission pattern and genetic characteristic of CP-Kpn in the hospital during the outbreak period. Whole-genome sequencing was retrospectively performed on 173 CP-Kpn isolates. Pairwise single-nucleotide polymorphism (SNP) distances were calculated to determine SNP thresholds for clustering. Plasmids and mobile genome elements (MGEs) were identified through short- and long-read sequencing. Strains were classified into three groups, sequence type 11 (ST11) (86.12%), ST15 (9.83%), and other ST. An SNP threshold of 16 revealed a 66.47% clustering rate. ICU admission and meropenem use proportions were significantly higher in clustered patients than in unique patients. MGE distribution was consistent with the phylogenetic tree. Of the isolates, 53.18% were CP-Kpn with hypervirulence genes. We identified five plasmids carrying virulence genes, and four of them have not been previously reported. Clonal transmission was the main cause of CP-Kpn infections in the hospital. Multidrug resistance genes and MGE variations were correlated with clustering. Finally, four novel plasmids carrying virulence genes were identified. The findings highlight the control of CR-Kpn transmission through prevention measures to reduce nosocomial infections. IMPORTANCE In this study, we combined genomic and epidemiological analyses and defined an optimal cutoff value for SNP difference that could be used to aid investigation in tertiary hospital in China. We revealed clonal transmission was the main cause of CP-Kpn infections in the hospital and identified four novel plasmids carrying virulence genes. Our results strongly suggested that dominant CP K. pneumoniae strains lead to outbreaks and described different evolutionary patterns of plasmids carrying multidrug resistance and virulence genes.

Dataset Information

Comparative analysis of Klebsiella pneumoniae strains isolated in 2012-2016 that differ by antibiotic resistance genes and virulence genes profiles.

Publications

Comparative analysis of Klebsiella pneumoniae strains isolated in 2012-2016 that differ by antibiotic resistance genes and virulence genes profiles.

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