Biology subjects

Gaur, R.

Publications and source records attributed to Gaur, R..

3 recordsLinked to original sources

bioRxiv2021

Evolutionary dynamics of Begomoviruses causing Papaya leaf curl disease in India

The genus begomovirus represents a group of multipartite viruses that significantly damages many agricultural crops, including papaya and drastically influence the overall production. Understanding the genetic variations, mutations and recombination of the begomovirus population infecting papaya has several important implications in alleviating substantial losses, mainly in developing countries, including India. In an attempt for a bioinformatics driven study of diversity and variability of papaya leaf curl disease in India, a total of thirty-two (32) DNA-A and sixteen (16) betasatellite sequences were retrieved from GenBank. An uneven distribution of evolutionary divergence has been observed across the branch length, which triggered the estimated recombinational event. Interestingly, a maximum of the begomoviruses were found to be intra-species recombinants. Further genetic variability, selection pressure, and substitution rate acting on the population were estimated and found to be high enough to support the evolution of geminiviruses. Genetic divergence composition in all begomovirus datasets revealed predominance of nucleotide diversity driven by mutation. The analysis indicates that even though a significant fraction of the genetic variations might be due to recombination but, it was constantly lower than the mutation rate. Thus, the diversification of the begomovirus population is principally impelled by mutational dynamics.

pathology↗

bioRxiv2020

Xpert MTB/XDR: A ten-color reflex assay suitable for point of care settings to detect isoniazid-, fluoroquinolone-, and second line injectable drug-resistance directly from Mycobacterium tuberculosis positive sputum.

We describe the design, development, analytical performance and a limited clinical evaluation of the 10-color Xpert MTB/XDR assay (CE-IVD only, not for sale in the US). This assay is intended as a reflex test to detect resistance to Isoniazid (INH), Fluoroquinolones (FLQ), Ethionamide (ETH) and Second Line Injectable Drugs Drugs (SLID) on unprocessed sputum samples and concentrated sputum sediments which are positive for Mycobacterium tuberculosis. The Xpert MTB/XDR assay simultaneously amplifies eight genes and promoter regions in M. tuberculosis and analyzes melting temperatures (Tms) using sloppy molecular beacon probes (SMB) to identify mutations associated with INH, FLQ, ETH and SLID resistance. Results can be obtained under 90 minutes and requires 10-color GeneXpert modules. The assay can differentiate low versus high-level resistance to INH and FLQ as well as cross-resistance versus individual resistance to SLIDs by identifying mutation-specific Tms or Tm patterns generated by the SMB probes. The assay has a Limit of Detection comparable to the Xpert MTB/RIF assay and succesfully detected 16 clinically significant mutations in a challenge set of clinical isolate DNA. In a clinical study performed at two sites with 100 sputum and 214 clinical isolates, the assay showed a sensitivity of 94-100% and a specificity of 100% for all drugs except for ETH when compared to sequencing. The sensitivity and specificity when compared to phenotypic drug susceptibility testing were in the same range. Used in combination with a primary tuberculosis diagnostic test, this assay is expected to expand the capacity for detection of drug-resistant tuberculosis.

microbiology↗

bioRxiv2018

Diverse Mechanisms of Resistance in Carbapenem-Resistant Enterobacteriaceae at a Health Care System in Silicon Valley, California

Carbapenem-resistant Enterobacteriaceae (CRE) are emerging as a major health threat in North America. The mechanism of resistance to carbapenems has therapeutic and public health implications. We comprehensively characterized the underlying mechanisms of carbapenem resistance in CRE isolates recovered between 2013 and 2016 at a health system in Northern California. Genotypic methods were used to detect carbapenemases and plasmid-encoded cephalosporinases, and mass spectrometry was used to quantify relative porin levels for OmpC and OmpF and their analogs. MICs for imipenem-relebactam, meropenem-vaborbactam, ceftazidime-avibactam, and ceftolozane-tazobactam were measured. Whole genome sequencing was used for strain typing. A carbapenemase gene encoding blaOXA-48 like, blaNDM, blaKPC, blaSME, blaIMP, and blaVIM was detected in 38.7% (24/62) of CRE isolates. Porin levels was down at least 2-fold in 91.9% (57/62) of isolates. Including carbapenemase genes and porin loss, the mechanism of resistance was identified in 95.2% (59/62) of CRE isolates. Of the carbapenemase gene-positive isolates, blaKPC -positive isolates were 100% susceptible to ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam; blaOXA-48 like-positive isolates were 100% susceptible to ceftazidime-avibactam; and blaSME-positive isolates were 100% susceptible to meropenem-vaborbactam and ceftolozane-tazobactam. 100% (38/38), 92.1% (35/38), 89.5% (34/38), and 31.6% (12/38) of carbapenemase gene-negative CRE isolates were susceptible to ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, and ceftolozane-tazobactam, respectively. None of the CRE strains were genetically identical. In conclusion, at this health system in Silicon Valley, carbapenemase-producing CRE occurred sporadically and were mediated by diverse mechanisms. Nucleic acid testing for blaOXA-48 like, blaNDM, blaKPC, blaIMP, and blaVIM was sufficient to distinguish between carbapenemase-producing and non-producing CRE and accurately predicted susceptibility to ceftazidime-avibactam, meropenem-vaborbactam and imipenem-relebactam.

microbiology↗