Biology subjects

Harshegyi, T.

Publications and source records attributed to Harshegyi, T..

4 recordsLinked to original sources

bioRxiv2023

Genomic dissection of endemic carbapenem resistance: metallo-beta-lactamase gene dissemination through clonal, plasmid and integron transfer pathways

Infections caused by metallo-beta-lactamase-producing organisms (MBLs) are a global health threat. Our understanding of transmission dynamics and how MBLs establish endemicity remains limited. We analysed two decades of blaIMP-4 evolution in a hospital using sequence data from 270 clinical and environmental isolates (including 169 completed genomes) and identified extreme gene promiscuity across 7 Gram-negative genera, 68 bacterial strains and 7 distinct plasmid types. An initial multi-species outbreak of conserved IncC plasmids (95 genomes across 37 strains) allowed endemicity to be established through the ability of blaIMP-4 to disseminate in successful strain-genetic setting pairs we termed propagators, in particular Serratia marcescens and Enterobacter hormaechei. From this reservoir, blaIMP-4 persisted through diversification of genetic settings that resulted from transfer of blaIMP-4 plasmids between bacterial hosts and of the integron carrying blaIMP-4 between plasmids. Our findings provide a framework for understanding endemicity and spread of MBLs and may have broader applicability to other carbapenemase-producing organisms.

microbiology↗

bioRxiv2022

Direct inference and control of genetic population structure from RNA sequencing data

RNAseq data can be used to infer genetic variants, yet its use for estimating genetic population structure remains underexplored. Here, we construct a freely available computational tool (RGStraP) to estimate RNAseq-based genetic principal components (RG-PCs) and assess whether RG-PCs can be used to control for population structure in gene expression analyses. Using whole blood samples from understudied Nepalese populations and the Geuvadis study, we show that RG-PCs had comparable results to paired array-based genotypes, with high genotype concordance and high correlations of genetic principal components, capturing subpopulations within the dataset. In differential gene expression analysis, we found that inclusion of RG-PCs as covariates reduced test statistic inflation. Our paper demonstrates that genetic population structure can be directly inferred and controlled for using RNAseq data, thus facilitating improved retrospective and future analyses of transcriptomic data.

bioinformatics↗

bioRxiv2021

A curated collection of Klebsiella metabolic models reveals variable substrate usage and gene essentiality

The Klebsiella pneumoniae species complex (KpSC) is a set of seven Klebsiella taxa which are found in a variety of niches, and are an important cause of opportunistic healthcare-associated infections in humans. Due to increasing rates of multi-drug resistance within the KpSC, there is a growing interest in better understanding the biology and metabolism of these organisms to inform novel control strategies. We collated 37 sequenced KpSC isolates isolated from a variety of niches, representing all seven taxa. We generated strain-specific genome scale metabolic models (GEMs) for all 37 isolates and simulated growth phenotypes on 511 distinct carbon, nitrogen, sulphur and phosphorus substrates. Models were curated and their accuracy assessed using matched phenotypic growth data for 94 substrates (median accuracy of 96%). We explored species-specific growth capabilities and examined the impact of all possible single gene deletions on growth in 145 core carbon substrates. These analyses revealed multiple strain-specific differences, within and between species and highlight the importance of selecting a diverse range of strains when exploring KpSC metabolism. This diverse set of highly accurate GEMs could be used to inform novel drug design, enhance genomic analyses, and identify novel virulence and resistance determinants. We envisage that these 37 curated strain-specific GEMs, covering all seven taxa of the KpSC, provide a valuable resource to the Klebsiella research community.

microbiology↗

bioRxiv2020

Klebsiella MALDI TypeR: a web-based tool for Klebsiella identification based on MALDI-TOF mass spectrometry

MotivationKlebsiella species are increasingly multidrug resistant pathogens affecting human and animal health and are widely distributed in the environment. Among these, the Klebsiella pneumoniae species complex (KpSC), which includes seven phylogroups, is an important cause of community and hospital infections. In addition, the Klebsiella oxytoca species complex (KoSC) also causes hospital infections and antibiotic-associated haemorrhagic colitis. The unsuitability of widely used clinical microbiology methods to distinguish species within each of these species complexes leads to high rates of misidentifications that are masking the true clinical significance and potential epidemiological specificities of individual species. ResultsWe developed a web-based tool, Klebsiella MALDI TypeR, a platform-independent and user-friendly application that enables uploading raw data from MALDI-TOF mass spectrometer to identify Klebsiella isolates at the species complex and phylogroup levels. The tool is based on a database of previously identified biomarkers that are specific for either the species complex, individual phylogroups, or related phylogroups, and is available at https://maldityper.pasteur.fr.

bioinformatics↗