Multidrug-Resistant Klebsiella pneumoniae ST307 in Traveler Returning from Puerto Rico to Dominican Republic.
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ABSTRACT:
SUBMITTER: Rojas R
PROVIDER: S-EPMC6649323 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundIn cystic fibrosis (CF), the spectrum and frequency of CFTR variants differ by geography and race/ethnicity. CFTR variants in White patients are well-described compared with Latino patients. No studies of CFTR variants have been done in patients with CF in the Dominican Republic or Puerto Rico.MethodsCFTR was sequenced in 61 Dominican Republican patients and 21 Puerto Rican patients with CF and greater than 60 mmol/L sweat chloride. The spectrum of CFTR variants was identified and the proportion of patients with 0, 1, or 2 CFTR variants identified was determined. The functional effects of identified CFTR variants were investigated using clinical annotation databases and computational prediction tools.ResultsOur study found 10% of Dominican patients had two CFTR variants identified compared with 81% of Puerto Rican patients. No CFTR variants were identified in 69% of Dominican patients and 10% of Puerto Rican patients. In Dominican patients, there were 19 identified CFTR variants, accounting for 25 out of 122 disease alleles (20%). In Puerto Rican patients, there were 16 identified CFTR variants, accounting for 36 out of 42 disease alleles (86%) in Puerto Rican patients. Thirty CFTR variants were identified overall. The most frequent variants for Dominican patients were p.Phe508del and p.Ala559Thr and for Puerto Rican patients were p.Phe508del, p.Arg1066Cys, p.Arg334Trp, and p.I507del.ConclusionsIn this first description of the CFTR variants in patients with CF from the Dominican Republic and Puerto Rico, there was a low detection rate of two CFTR variants after full sequencing with the majority of patients from the Dominican Republic without identified variants.
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Project description:We report here the draft genome sequence of Acinetobacter baumannii strain M3AC14-8, sequence type 2 (ST2), carrying a chromosomally carried blaKPC-2 gene. The draft genome consists of a total length of 4.11 Mbp and a G+C content of 39.25%.
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Project description:ResumoThe Klebsiella pneumoniae (K. pneumoniae) bacterium is responsible for many opportunistic infections such as sepsis, and a multidrug-resistant (MDR) clone sequence type (ST) 307 has recently begun to spread. The objective of this study was to report the first occurrence of this virulent genotype, which was found in the context of a urinary infection in a domestic feline in Brazil. The K. pneumoniae isolate was identified from the urine of a 6-month-old male crossbreed cat using 16S rRNA sequencing. It was then subjected to antimicrobial susceptibility testing, followed by multilocus sequence typing analysis, and PCR detection of virulence and resistance genes. The antimicrobial susceptibility profile demonstrated that the isolate was MDR and associated with the presence of the colistin resistance gene (mcr-1). Genotyping allowed us to classify the isolate as K. pneumoniae ST307 with the presence of wabG, uge, and entB genes. MDR K. pneumoniae is important in human and veterinary medicine because it causes many types of infections. Clonal propagation of virulent or MDR genotypes such as K. pneumoniae ST307 is a global concern. This report of ST307 isolation from a urine sample in a domestic feline is the first in Brazil.
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Project description:Klebsiella pneumoniae sequence type (ST) 307 is an emerging global antimicrobial drug-resistant clone. We used whole-genome sequencing and PCR to characterize K. pneumoniae ST307 with oxacillinase (OXA) 181 carbapenemase across several private hospitals in South Africa during 2014-2016. The South Africa ST307 belonged to a different clade (clade VI) with unique genomic characteristics when compared with global ST307 (clades I-V). Bayesian evolution analysis showed that clade VI emerged around March 2013 in Gauteng Province, South Africa, and then evolved during 2014 into 2 distinct lineages. K. pneumoniae ST307 clade VI with OXA-181 disseminated over a 15-month period within 42 hospitals in 23 cities across 6 northeastern provinces, affecting 350 patients. The rapid expansion of ST307 was most likely due to intrahospital, interhospital, intercity, and interprovince movements of patients. This study highlights the importance of molecular surveillance for tracking emerging antimicrobial clones.
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Project description:Dominicans are the largest migrant community in Puerto Rico, yet understudied. We compared risk factors and health conditions of Dominicans versus Puerto Ricans (PRs). Cross-sectional survey of Dominicans (n?=?55) and PRs (n?=?310) aged 30-75 years, assessed with validated questionnaires and standardized anthropometric measurements. Significantly, more Dominicans than PRs had attained <8th grade education (37.7 vs. 8.0%), reported household income ?$10,000 (76.1 vs. 56.9%), lacked health insurance (19.6 vs. 5.5%), and reported food insecurity (24.5 vs. 12.1%). They spent fewer hours/day watching television (2.9 vs. 3.8), and were less likely to smoke (7.6 vs. 19.6%). Medically-diagnosed depression was lower among Dominicans than PRs (9.6 vs. 23.0%); questionnaire-based high depressive symptomatology was similar (47.9 vs. 52.8%). Dominicans living in Puerto Rico had more socioeconomic risk factors but healthier lifestyle behaviors and lower prevalence of medically-diagnosed depression than PRs. Tailored approaches are needed to ameliorate disparities in each ethnic group.
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Project description:From June to October 2019, 17 patients (six infected, 11 colonised) with an extensively drug-resistant (XDR) Klebsiella pneumoniae strain were notified from four Western Pomerania medical facilities. The XDR K. pneumoniae produced carbapenemases NDM-1 and OXA-48, and was only susceptible to chloramphenicol, tigecycline and cefiderocol. Synergistic activity was observed for the combination of aztreonam plus ceftazidime-avibactam. Genomic analyses showed all isolates belonged to K. pneumoniae sequence type 307. Control measures and further investigations are ongoing.
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Project description:OBJECTIVES:Recent reports indicate the emergence of a new carbapenemase-producing Klebsiella pneumoniae clone, ST307. We sought to better understand the global epidemiology and evolution of this clone and evaluate its association with antimicrobial resistance (AMR) genes. METHODS:We collated information from the literature and public databases and performed a comparative analysis of 95 ST307 genomes (including 37 that were newly sequenced). RESULTS:We show that ST307 emerged in the mid-1990s (nearly 20?years prior to its first report), is already globally distributed and is intimately associated with a conserved plasmid harbouring the blaCTX-M-15 ESBL gene and several other AMR determinants. CONCLUSIONS:Our findings support the need for enhanced surveillance of this widespread ESBL clone in which carbapenem resistance has occasionally emerged.
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Project description:Resistance to the ceftazidime (CAZ)-avibactam (AVI) combination is increasingly being reported. Here, we report a CAZ-AVI-resistant Klebsiella pneumoniae strain belonging to the high-risk sequence type 307 (ST307) clone and producing Klebsiella pneumoniae carbapenemase 39 (KPC-39), a single-amino-acid variant of KPC-3 (A172T). Cloning experiments, steady-state kinetic parameters, and molecular dynamics simulations revealed a loss of carbapenemase activity and increased affinity for CAZ. KPC-39 was identified in a patient without prior exposure to CAZ-AVI, suggesting silent dissemination in European health care settings.
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Project description:The global spread of Klebsiella pneumoniae producing Klebsiella pneumoniae carbapenemase (KPC) has been mainly associated with the dissemination of high-risk clones. In the last decade, hospital outbreaks involving KPC-producing K. pneumoniae have been predominantly attributed to isolates belonging to clonal group (CG) 258. However, results of recent epidemiological analysis indicate that KPC-producing sequence type (ST) 307, is emerging in different parts of the world and is a candidate to become a prevalent high-risk clone in the near future. Here we show that the ST307 genome encodes genetic features that may provide an advantage in adaptation to the hospital environment and the human host. Sequence analysis revealed novel plasmid-located virulence factors, including a cluster for glycogen synthesis. Glycogen production is considered to be one of the possible adaptive responses to long-term survival and growth in environments outside the host. Chromosomally-encoded virulence traits in the clone comprised fimbriae, an integrative conjugative element carrying the yersiniabactin siderophore, and two different capsular loci. Compared with the ST258 clone, capsulated ST307 isolates showed higher resistance to complement-mediated killing. The acquired genetic features identified in the genome of this new emerging clone may contribute to increased persistence of ST307 in the hospital environment and shed light on its potential epidemiological success.
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Project description:Klebsiella pneumoniae causes severe lung and bloodstream infections that are difficult to treat due to multidrug resistance. We hypothesized that antimicrobial resistance can be reversed by targeting chromosomal non-essential genes that are not responsible for acquired resistance but essential for resistant bacteria under therapeutic concentrations of antimicrobials. Conditional essentiality of individual genes to antimicrobial resistance was evaluated in an epidemic multidrug-resistant clone of K. pneumoniae (ST258). We constructed a high-density transposon mutant library of >430,000 unique Tn5 insertions and measured mutant depletion upon exposure to three clinically relevant antimicrobials (colistin, imipenem or ciprofloxacin) by Transposon Directed Insertion-site Sequencing (TraDIS). Using this high-throughput approach, we defined three sets of chromosomal non-essential genes essential for growth during exposure to colistin (n = 35), imipenem (n = 1) or ciprofloxacin (n = 1) in addition to known resistance determinants, collectively termed the "secondary resistome". As proof of principle, we demonstrated that inactivation of a non-essential gene not previously found linked to colistin resistance (dedA) restored colistin susceptibility by reducing the minimum inhibitory concentration from 8 to 0.5 μg/ml, 4-fold below the susceptibility breakpoint (S ≤ 2 μg/ml). This finding suggests that the secondary resistome is a potential target for developing antimicrobial "helper" drugs that restore the efficacy of existing antimicrobials.
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