Biology subjects

Riley, L. W.

Publications and source records attributed to Riley, L. W..

3 recordsLinked to original sources

bioRxiv2024

Mycolic acid and cholesterol induced transcriptomic adaptations in wild type and Mce complex ATPase subunit deleted strain of M. tuberculosis H37Rv

During infection and latency, Mycobacterium tuberculosis (Mtb) primarily relies on lipids as its main energy source. The Mtb mammalian cell entry (Mce) complexes function as lipid transporters with Mkl as the ATPase subunit for substrate translocation. Cholesterol and mycolic acid are essential to the infectiousness and pathogenicity of Mtb. Here, we have investigated the transcriptomic responses of wild type and{Delta} mkl strains of Mtb to cholesterol and mycolic acid through RNAseq analysis. The number of differentially expressed genes was always higher when grown on cholesterol than on mycolic acid. In most cases,{Delta} mkl showed the opposite gene expression pattern compared to the wild type. Among the four mce operons, significant changes in expression patterns were observed mainly in the genes of mce3 and mce4 operons. The upregulation of mce3 operon and the downregulation of mce4 operon in the presence of mycolic acid and cholesterol is intriguing. The transcriptome profile of genes involved in mycolic acid synthesis did not show significant change to either mycolic acid or cholesterol. However, interestingly, both mycolic acid and cholesterol induce upregulation of methyl citrate cycle and dormancy related genes indicating their significance during Mtb persistence and provides insights on Mtbs adaptive strategies under stress through transcriptional remodelling.

biochemistry↗

bioRxiv2021

Genetic features of persistently antimicrobial drug-susceptible extraintestinal pathogenic Escherichia coli pandemic sequence type 95

Extraintestinal pathogenic Escherichia coli (ExPEC) belonging to multilocus sequence type 95 (ST95) is one of the most geographically widespread ExPEC lineages causing bloodstream (BSI) and urinary tract infections (UTI). In contrast to other widespread ExPEC sequence types, a large proportion ST95 strains remains susceptible to all antimicrobial agents used to treat BSI or UTI. We aimed to identify genomic features of ST95 associated with its relatively high drug-susceptible frequency. We analyzed whole genomes of 1749 ST95 isolates, 80 from patients with BSI or UTI in Northern California, and 1669 isolates from the Enterobase database. We first compared whole-genome sequences (WGS) of 887 drug-susceptible strains and 862 strains resistant to one or more drugs (defined genotypically as strains harboring drug-resistance genes annotated in the ResFinder database) to identify genetic features associated with strains devoid of drug-resistance genes. We then conducted a pan-genome-wide association study on human clinical isolates of ST95, which included 553 UTI and BSI ST95 isolates. We found 44 accessory genes to be significantly associated with ST95 strains lacking drug resistance genes. Fifteen of these were not found in any of the WGSs of ST131 ExPEC strains, which are frequently multidrug-resistant. These genes were annotated to encode transporter or transfer systems and DNA repair polymerases. A large proportion of ST95 strains may have evolved to adapt to antibiotic-imposed stresses without acquiring drug-resistance genes. ImportanceDespite the increasing prevalence of antibiotic-resistant Escherichia coli strains that cause urinary tract and bloodstream infections, a major pandemic lineage of extraintestinal pathogenic E. coli (ExPEC) ST95 has a comparatively low frequency of drug resistance. We compared genomes of 1749 ST95 isolates to identify genetic features that may explain why most strains of ST95 resist becoming drug-resistant. Identification of such genomic features could contribute to the development of novel strategies to prevent the spread of antibiotic-resistant genes and devise new measures to control antibiotic-resistant infections.

bioinformatics↗

bioRxiv2019

Prevalence of beta-lactam drug-resistance genes in commensal Escherichia coli contaminating ready-to-eat lettuce

The objective of this study was to evaluate the prevalence of antibiotic resistance and beta-lactam drug resistance genes in Escherichia coli isolated from ready-to-eat lettuce, obtained from local supermarkets in Northern California. Bags of lettuce were purchased from 4 chain supermarkets during three different periods--Oct 2018-Jan 2019, Feb 2019-Apr 2019 and May 2019-July 2019. From 91 packages of lettuce, we recovered 34 E. coli isolates from 22 (24%) lettuce samples. All E. coli isolates were genotyped by multilocus sequence typing (MLST), and we found 15 distinct sequence types (STs). Five of these genotypes (ST2819, ST4600, ST2432, ST1198 and ST5143) have been reported to cause infection in humans. Twenty (59%) E. coli isolates were found resistant to at least one of the antibacterial drugs. They included resistance to ampicillin (AMP, 85%) and ampicillin/sulbactam (SAM, 50%), cefoxitin (FOX, 40%) and cefuroxime (CXM, 35%). We found 8 (40%) of 20 beta-lactam resistant E. coli isolates to carry blaCTX-M; 5 (25%) tested positive for blaSHV, while only 4 (20%) tested positive for blaTEM. Additionally, we identified a class A broad-spectrum beta-lactamase SED-1 gene, blaSED, reported by others in Citrobacter sedlakii isolated from bile of a patient. This study found that a large proportion of fresh lettuce carry beta-lactam drug-resistant E. coli, which could serve as a reservoir for drug resistance genes that could potentially enter pathogens to cause human infections.

microbiology↗