scholarly journals Molecular Epidemiological Analysis of ST11-K64 Extensively Drug-Resistant Klebsiella pneumoniae Infections Outbreak in Intensive Care and Neurosurgery Units Based on Whole-Genome Sequencing

2021 ◽  
Vol 12 ◽  
Author(s):  
Liuxin Xiong ◽  
Lebin Su ◽  
Hanqing Tan ◽  
Wansha Zhao ◽  
Shuying Li ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genetic Relatedness ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
Phenotypic Traits ◽  
Whole Genome ◽  
Drug Resistant ◽  
Extensively Drug Resistant

Klebsiella pneumoniae (Kp) is the primary causative bacteria for nosocomial infections and hospital outbreaks. In particular, extensively drug-resistant K. pneumoniae (XDRKp) causes severe clinical infections in hospitalized patients. Here, we used pulsed-field gel electrophoresis (PFGE), drug susceptibility tests, and the whole-genome sequencing (WGS) technology to examine genetic relatedness and phenotypic traits of the strains isolated during an outbreak period. Based on PFGE, a distinct clones cluster comprised of eight XDRKp was observed. These strains were confirmed as ST11-K64 via multiple-locus sequence typing database of Kp. The strains also had genes related to the regulation of biofilm biosynthesis (type 1 & 3 fimbriae, type IV pili biosynthesis, RcsAB, and type VI secretion system) and multiple drug resistance (β-lactamase and aminoglycoside antibiotic resistance). WGS data based on core-single nucleotide polymorphisms and epidemiological investigation showed that the neurosurgery unit was likely the source of the outbreak, the strain was likely to have been transmitted to the ICU through patients. In addition, the two highly probable transmission routes were in the ICU (exposure through shared hospital beds) and the neurosurgery units (all cases were treated by the same rehabilitation physician and were most likely infected during the physical therapy). Notably, the bed mattress had played a crucial transmission role of this outbreak, served as a pathogen reservoir.

scholarly journals Multifactorial Chromosomal Variants Regulate Polymyxin Resistance in Extensively Drug-Resistant Klebsiella pneumoniae

2017 ◽  
Author(s):  
Miranda E Pitt ◽  
Alysha G Elliott ◽  
Minh Duc Cao ◽  
Devika Ganesamoorthy ◽  
Ilias Karaiskos ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Clinical Isolates ◽  
Whole Genome ◽  
Drug Resistant ◽  
Missense Mutations ◽  
Novel Mutations ◽  
Suppressor Mutations ◽  
Extensively Drug Resistant

ABSTRACTExtensively drug-resistant Klebsiella pneumoniae (XDR-KP) infections cause high mortality and are disseminating globally. Identifying the genetic basis underpinning resistance allows for rapid diagnosis and treatment. XDR isolates sourced from Greece and Brazil, including nineteen polymyxin-resistant and five polymyxin-susceptible strains, underwent whole genome sequencing. Approximately 90% of polymyxin resistance was enabled by alterations upstream or within mgrB. The most common mutation identified was an insertion at nucleotide position 75 in mgrB via an ISKpn26-like element in the ST258 lineage and ISKpn13 in one ST11 isolate. Three strains acquired an IS1 element upstream of mgrB and another strain had an ISKpn25 insertion at 133 bp. Other isolates had truncations (C28STOP, Q30STOP) or a missense mutation (D31E) affecting mgrB. Complementation assays revealed all mgrB perturbations contributed to resistance. Missense mutations in phoQ (T281M, G385C) were also found to facilitate resistance. Several variants in phoPQ co-segregating with the ISKpn26-like insertion were identified as potential partial suppressor mutations. Three ST258 samples were found to contain subpopulations with different resistance conferring mutations, including the ISKpn26-like insertion colonising with a novel mutation in pmrB (P158R), both confirmed via complementation assays. We also characterized a new multi-drug resistant Klebsiella quasipneumoniae strain ST2401 which was susceptible to polymyxins. These findings highlight the broad spectrum of chromosomal modifications which can facilitate and regulate resistance against polymyxins in K. pneumoniae.DATA SUMMARYWhole genome sequencing of the 24 clinical isolates has been deposited under BioProject PRJNA307517 (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA307517).IMPACT STATEMENTKlebsiella pneumoniae contributes to a high abundance of nosocomial infections and the rapid emergence of antimicrobial resistance hinders treatment. Polymyxins are predominantly utilized to treat multidrug-resistant infections, however, resistance to the polymyxins is arising. This increasing prevalence in polymyxin resistance is evident especially in Greece and Brazil. Identifying the genomic variations conferring resistance in clinical isolates from these regions assists with potentially detecting novel alterations and tracing the spread of particular strains. This study commonly found mutations in the gene mgrB, the negative regulator of PhoPQ, known to cause resistance in KP. In the remaining isolates, missense mutations in phoQ were accountable for resistance. Multiple novel mutations were detected to be segregating with mgrB perturbations. This was either due to a mixed heterogeneous sample of two polymyxin-resistant strains, or because of multiple mutations within the same strain. Of interest was the validation of novel mutations inphoPQ segregating with a previously known ISKpn26-like element in disrupted mgrB isolates. Complementation of these phoPQ mutations revealed a reduction in minimum inhibitory concentrations and suggests the first evidence of partial suppressor mutations in KP. This research builds upon our current understanding of heteroresistance, lineage specific mutations and regulatory variations relating to polymyxin resistance.

Extensively drug-resistant Acinetobacter baumannii isolated from intensive care units in northern Italy: a genomic approach to characterize new sequence types

2019 ◽  
Vol 14 (15) ◽  
pp. 1281-1292 ◽  
Author(s):  
Giovanni Lorenzin ◽  
Erika Scaltriti ◽  
Franco Gargiulo ◽  
Francesca Caccuri ◽  
Giorgio Piccinelli ◽  
...  
Keyword(s):  
Intensive Care ◽  
Whole Genome Sequencing ◽  
Acinetobacter Baumannii ◽  
Intensive Care Units ◽  
Genome Sequencing ◽  
Multilocus Sequence Typing ◽  
Whole Genome ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Sequence Types

Aim: This study aims to characterize clinical strains of Acinetobacter baumannii with an extensively drug-resistant phenotype. Methods: VITEK® 2, Etest® method and broth microdilution method for colistin were used. PCR analysis and multilocus sequence typing Pasteur scheme were performed to identify bla-OXA genes and genetic relatedness, respectively. Whole-genome sequencing analysis was used to characterize three isolates. Results: All the isolates were susceptible only to polymyxins. blaOXA-23-like gene was the only acquired carbapenemase gene in 88.2% of the isolates. Multilocus sequence typing identified various sequence types: ST2, ST19, ST195, ST577 and ST632. Two new sequence types, namely, ST1279 and ST1280, were detected by whole-genome sequencing. Conclusion: This study showed that carbapenem-resistant A. baumannii isolates causing infections in intensive care units almost exclusively produce OXA-23, underlining their frequent spread in Italy.

scholarly journals Genome Sequencing of Polydrug-, Multidrug-, and Extensively Drug-Resistant Mycobacterium tuberculosis Strains from South India

2019 ◽  
Vol 8 (12) ◽  
Author(s):  
Sivakumar Shanmugam ◽  
Narender Kumar ◽  
Dina Nair ◽  
Mohan Natrajan ◽  
Srikanth Prasad Tripathy ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
South India ◽  
Sequence Data ◽  
Whole Genome ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Content Type ◽  
Extensively Drug Resistant

The genomes of 16 clinical Mycobacterium tuberculosis isolates were subjected to whole-genome sequencing to identify mutations related to resistance to one or more anti-Mycobacterium drugs. The sequence data will help in understanding the genomic characteristics of M. tuberculosis isolates and their resistance mutations prevalent in South India.

scholarly journals Whole Genome Sequencing Based Characterization of Extensively Drug-Resistant Mycobacterium tuberculosis Isolates from Pakistan

PLoS ONE ◽  
2015 ◽  
Vol 10 (2) ◽  
pp. e0117771 ◽  
Author(s):  
Asho Ali ◽  
Zahra Hasan ◽  
Ruth McNerney ◽  
Kim Mallard ◽  
Grant Hill-Cawthorne ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Drug Resistant ◽  
Extensively Drug Resistant

scholarly journals Genomic investigation of a suspected multi-drug resistant Klebsiella pneumoniae outbreak in a neonatal care unit in sub-Saharan Africa

2020 ◽  
Author(s):  
Jennifer Cornick ◽  
Patrick Musicha ◽  
Chikondi Peno ◽  
Ezgi Saeger ◽  
Pui-ying Iroh Toh ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Resistance Genes ◽  
Sub Saharan Africa ◽  
Whole Genome ◽  
Drug Resistant ◽  
Sub Saharan ◽  
Neonatal Care Unit ◽  
Suspected Outbreak

ABSTRACTA suspected outbreak of multi-drug resistant (MDR) Klebsiella pneumoniae in a Malawian neonatal unit was investigated using whole-genome sequencing. Strain-types, virulence and resistance genes of K. pneumoniae isolated from patients from the hospital over a four-year period were identified. A MDR ST340 clone was implicated as the likely outbreak cause.

Whole genome analysis of extensively drug-resistant Acinetobacter bau-mannii clinical isolates in Thailand

2020 ◽  
Vol 20 ◽  
Author(s):  
Peechanika Chopjitt ◽  
Anusak Kerdsin ◽  
Dan Takeuchi ◽  
Rujirat Hatrongjit ◽  
Parichart Boueroy ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Acinetobacter Baumannii ◽  
Genome Sequencing ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Whole Genome ◽  
Drug Resistant ◽  
Resistant Genes ◽  
Extensively Drug Resistant ◽  
Antibiotic Efflux

Background:: Acinetobacter baumannii is recognized as a majority opportunistic nosocomial pathogen and caus-ing hospital-acquired infection worldwide. The increasing prevalence of extensively drug-resistant Acinetobacter baumannii (XDRAB) has become a rising concern in healthcare facilities and has impeded public health due to limitation of therapeutic options and are associated with high morbidity and mortality as well as longer hospitalization. Whole-genome sequencing of highly multidrug resistant A. baumannii will increase understanding of resistant mechanisms, the emergence of novel re-sistance, genetic relationships among the isolates, source tracking, and treatment decisions in selected patients. Objective:: This study revealed the genomic analysis to explore blaOXA-23 harboring XDRAB isolates in Thailand. Methods:: Whole-genome sequencing of the two XDRAB isolates was carried out on a HiSeq2000 Illumina platform and susceptibility on antimicrobials was conducted. Results:: Both isolates revealed sequence types of international, clone II-carrying, multiple antimicrobial-resistant genes—ST195 and ST451. They were resistant to antimicrobial agents in all drug classes tested for Acinetobacter spp. They carried 18 antimicrobial-resistant genes comprising of 4 -lactamase genes (blaOXA-23, blaOXA-66, blaTEM-1D, blaADC-25), 4 aminogly-coside-resistant genes (armA, aph(3')-Ia, aph(3'')-Ib, aph(6)-Id), 3 macrolide-resistant genes (amvA, mphE, msrE), 1 sulfon-amide-resistant gene (sul-2), 2 tetracycline-resistant genes (tetB, tetR), 1 resistant-nodulation-cell division (RND) antibiotic efflux pump gene cluster, 2 major facilitator superfamily (MFS) antibiotic efflux pump genes (abaF, abaQ), and 1 small multidrug-resistant (SMR) antibiotic efflux pump gene (abeS). Mutation of gyrA (S81L) occurred in both isolates. Conclusions:: Whole-genome sequencing revealed both blaOXA-23 harboring XDRAB isolates were clustered under interna-tional clone II with difference STs and carrying multiple antimicrobial-resistant genes conferred their resistance to antimi-crobial agents. Inactivation of antimicrobials and target modification by enzymes, and pumping antibiotics by efflux pump are mainly resistance mechanism of the XDRAB in this study.

scholarly journals Whole-Genome Sequencing Analysis of Serially Isolated Multi-Drug and Extensively Drug Resistant Mycobacterium tuberculosis from Thai Patients

PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0160992 ◽  
Author(s):  
Kiatichai Faksri ◽  
Jun Hao Tan ◽  
Areeya Disratthakit ◽  
Eryu Xia ◽  
Therdsak Prammananan ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Sequencing Analysis ◽  
Drug Resistant ◽  
Extensively Drug Resistant

scholarly journals Transmitted Extended-Spectrum Extensively Drug-Resistant Tuberculosis in Beijing, China, with Discordant Whole-Genome Sequencing Analysis Results

2015 ◽  
Vol 53 (8) ◽  
pp. 2781-2784 ◽  
Author(s):  
Hao Li ◽  
Masood ur Rehman Kayani ◽  
Yunting Gu ◽  
Xiaobo Wang ◽  
Ting Zhu ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Sequencing Analysis ◽  
Drug Resistant ◽  
Resistant Disease ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Extended Spectrum ◽  
Beijing China

Drug resistance to tuberculosis remains a major public health threat. Here, we report two cases of extended-spectrum extensively drug-resistant (XXDR) tuberculosis showing resistance to most first- and second-line agents. The results of a correlation of whole-genome sequencing (WGS) and phenotypic testing were discordant, suggesting that overreliance on WGS may miss clinically relevant resistance in extensively drug-resistant disease.

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