scholarly journals Loss of daptomycin susceptibility in clinical Staphylococcus epidermidis infection coincided with variants in WalK

2020 ◽  
Vol 2020 (1) ◽  
pp. 219-224
Author(s):  
Nicholas F Brazeau ◽  
Kara J Levinson ◽  
Asher Schranz ◽  
Kara A Moser ◽  
Ian Hollis ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Genome Sequencing ◽  
Staphylococcus Epidermidis ◽  
Single Gene ◽  
Multidrug Resistant ◽  
Prolonged Treatment ◽  
Whole Genome ◽  
Treatment Resistant ◽  
Staphylococcus Infections ◽  
Protein Configuration

Abstract Daptomycin (DAP) is key in treating multidrug-resistant Staphylococcus infections. Diminished susceptibility to DAP is emerging among Staphylococcus epidermidis strains although mechanisms for non-susceptibility (NS) remain poorly understood. We report a case of persistent S. epidermidis bacteremia in which loss of DAP susceptibility arose during prolonged treatment. Whole genome sequencing identified two mutations, Q371del and P415L, in a single-affected gene, WalK, that coincided with the emergence of DAP-NS. Protein modeling of the mutations predicted a disruption of WalK protein configuration. The emergence of mutations in a single-gene during DAP exposure raises concerns in an era of increasingly treatment-resistant infections. Lay summary: Daptomycin is an important antibiotic for fighting Staphylococcus infections. We identified variants in the WalK gene that were coincident with resistance in a clinical Staphylococcus epidermidis infection. Clinicians, hospital epidemiologists, and microbiology laboratories need to be aware of the potential for the evolution of drug resistance during prolonged daptomycin therapy.

scholarly journals Deep learning predicts tuberculosis drug resistance status from genome sequencing data

2018 ◽  
Author(s):  
Michael L. Chen ◽  
Akshith Doddi ◽  
Jimmy Royer ◽  
Luca Freschi ◽  
Marco Schito ◽  
...  
Keyword(s):  
Machine Learning ◽  
Drug Resistance ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Predictive Performance ◽  
Multidrug Resistant ◽  
Whole Genome ◽  
Second Line ◽  
Sequencing Data ◽  
First Line

AbstractBackgroundThe diagnosis of multidrug resistant and extensively drug resistant tuberculosis is a global health priority. Whole genome sequencing of clinicalMycobacteriumtuberculosis isolates promises to circumvent the long wait times and limited scope of conventional phenotypic antimicrobial susceptibility, but gaps remain for predicting phenotype accurately from genotypic data.Methods and FindingsUsing targeted or whole genome sequencing and conventional drug resistance phenotyping data from 3,601Mycobacterium tuberculosisstrains, 1,228 of which were multidrug resistant, we investigated the use of machine learning to predict phenotypic drug resistance to 10 anti-tuberculosis drugs. The final model, a multitask wide and deep neural network (MD-WDNN), achieved improved high predictive performance: the average AUCs were 0.979 for first-line drugs and 0.936 for second-line drugs during repeated cross-validation. On an independent validation set, the MD-WDNN showed average AUCs, sensitivities, and specificities, respectively, of 0.937, 87.9%, and 92.7% for first-line drugs and 0.891, 82.0% and 90.1% for second-line drugs. In addition to being able to learn from samples that have only been partially phenotyped, our proposed multidrug architecture shares information across different anti-tuberculosis drugs and genes to provide a more accurate phenotypic prediction. We uset-distributed Stochastic Neighbor Embedding (t-SNE) visualization and feature importance analyses to examine inter-drug similarities.ConclusionsMachine learning is capable of accurately predicting resistant status using genomic information and holds promise in bringing sequencing technologies closer to the bedside.

scholarly journals Clonal Emergence of Invasive Multidrug-Resistant Staphylococcus epidermidis Deconvoluted via a Combination of Whole-Genome Sequencing and Microbiome Analyses

2018 ◽  
Vol 67 (3) ◽  
pp. 398-406 ◽  
Author(s):  
Xiqi Li ◽  
Cesar A Arias ◽  
Samuel L Aitken ◽  
Jessica Galloway Peña ◽  
Diana Panesso ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Staphylococcus Epidermidis ◽  
Multidrug Resistant ◽  
Whole Genome

scholarly journals Whole-Genome Sequencing Reveals Recent Transmission of Multidrug-Resistant Mycobacterium tuberculosis CAS1-Kili Strains in Lusaka, Zambia

Antibiotics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 29
Author(s):  
Joseph Yamweka Chizimu ◽  
Eddie Samuneti Solo ◽  
Precious Bwalya ◽  
Wimonrat Tanomsridachchai ◽  
Herman Chambaro ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Regulatory Region ◽  
Multidrug Resistant ◽  
Epidemiological Methods ◽  
Whole Genome ◽  
Recent Transmission ◽  
Mdr Tb

Globally, tuberculosis (TB) is a major cause of death due to antimicrobial resistance. Mycobacterium tuberculosis CAS1-Kili strains that belong to lineage 3 (Central Asian Strain, CAS) were previously implicated in the spread of multidrug-resistant (MDR)-TB in Lusaka, Zambia. Thus, we investigated recent transmission of those strains by whole-genome sequencing (WGS) with Illumina MiSeq platform. Twelve MDR CAS1-Kili isolates clustered by traditional methods (MIRU-VNTR and spoligotyping) were used. A total of 92% (11/12) of isolates belonged to a cluster (≤12 SNPs) while 50% (6/12) were involved in recent transmission events, as they differed by ≤5 SNPs. All the isolates had KatG Ser315Thr (isoniazid resistance), EmbB Met306 substitutions (ethambutol resistance) and several kinds of rpoB mutations (rifampicin resistance). WGS also revealed compensatory mutations including a novel deletion in embA regulatory region (−35A > del). Several strains shared the same combinations of drug-resistance-associated mutations indicating transmission of MDR strains. Zambian strains belonged to the same clade as Tanzanian, Malawian and European strains, although most of those were pan-drug-susceptible. Hence, complimentary use of WGS to traditional epidemiological methods provides an in-depth insight on transmission and drug resistance patterns which can guide targeted control measures to stop the spread of MDR-TB.

scholarly journals Whole-Genome Sequencing of Two Moroccan Mycobacterium tuberculosis Strains

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
M. Laamarti ◽  
N. El Mrimar ◽  
T. Alouane ◽  
S. Kartti ◽  
E. Belouad ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Pulmonary Tuberculosis ◽  
Genome Sequencing ◽  
Extrapulmonary Tuberculosis ◽  
Draft Genome ◽  
Multidrug Resistant ◽  
Whole Genome ◽  
Genome Sequences ◽  
Content Type

ABSTRACT Mycobacterium tuberculosis is known to cause pulmonary and extrapulmonary tuberculosis. In Morocco, the spread of multidrug-resistant (MDR) tuberculosis (TB) has become a major challenge. Here, we announce the draft genome sequences of two Mycobacterium tuberculosis strains, MTB1 and MTB2, isolated from patients with pulmonary tuberculosis in Morocco, to describe variants associated with drug resistance.

scholarly journals Micro-costing diagnostics in oncology: from single-gene testing to whole genome sequencing

2021 ◽  
Author(s):  
Clémence TB Pasmans ◽  
Bastiaan BJ Tops ◽  
Elisabeth MP Steeghs ◽  
Veerle MH Coupé ◽  
Katrien Grünberg ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Single Gene ◽  
Whole Genome ◽  
Gene Testing

scholarly journals Molecular evaluation of drug resistance in clinical isolates of Salmonella enterica serovar Typhi from Pakistan

2013 ◽  
Vol 7 (12) ◽  
pp. 929-940 ◽  
Author(s):  
Amna Afzal ◽  
Yasra Sarwar ◽  
Aamir Ali ◽  
Abbas Maqbool ◽  
Muhammad Salman ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Nalidixic Acid ◽  
Salmonella Enterica ◽  
Single Gene ◽  
Mutation Screening ◽  
Gene Cassette ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Fourth Generation ◽  
Salmonella Enterica Serovar Typhi

Introduction: This study aimed to determine the drug susceptibility patterns and genetic elements related to drug resistance in isolates of Salmonella enterica serovar Typhi (S. Typhi) from the Faisalabad region of Pakistan. Methodology: The drug resistance status of 80 isolates were evaluated by determining antimicrobial susceptibility, MICs, drug resistance genes involved, and the presence of integrons. Nalidixic acid resistance and reduced susceptibility to ciprofloxacin were also investigated by mutation screening of the gyrA, gyrB, parC, and parE genes. Results: Forty-seven (58.7%) isolates were multidrug resistant (MDR). Among the different resistance (R) types, the most commonly observed (13/80) was AmChStrTeSxtSmzTmp, which is the most frequent type observed in India and Pakistan. The most common drug resistant genes were blaTEM-1, cat, strA-strB, tetB, sul1, sul2, and dfrA7. Among the detected genes, only dfrA7 was found to be associated in the form of a single gene cassette within the class 1 integrons. Conclusions: MIC determination of currently used drugs revealed fourth-generation gatifloxacin as an effective drug against multidrug-resistant S. Typhi, but its clinical use is controversial. The Ser83→Phe substitution in gyrA was the predominant alteration in nalidixic acid-resistant isolates, exhibiting reduced susceptibility and increased MICs against ciprofloxacin. No mutations in gyrB, parC, or parE were detected in any isolate.

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