Biology subjects

Kent, A. G.

Publications and source records attributed to Kent, A. G..

3 recordsLinked to original sources

bioRxiv2025

Evaluation of Enterobacterales carrying Acinetobacter-associated blaOXA genes--United States, 2017-2022

Through their ability to hydrolyze carbapenems, Ambler class D beta-lactamases endanger patients by limiting the clinical efficacy of beta-lactam antimicrobials. Further, plasmid-mediated transmission can increase mobility of carbapenemase genes between bacteria and facilitate their spread between patients. In the United States and elsewhere, the plasmid-mediated Ambler class D carbapenemase genes blaOXA-23-like, blaOXA-24/40-like, and blaOXA-58-like are commonly associated with Acinetobacter species and have rarely been reported outside of this genus. However, multiple recent international reports indicate detection of Enterobacterales isolates carrying Acinetobacter-associated class D carbapenemase genes. This evaluation aimed to provide insight into whether Enterobacterales harboring these class D genes may be circulating undetected in the United States, thereby signaling a need for adapting testing strategies to prioritize the detection of these potentially emerging public health threats. We analyzed whole-genome sequencing data generated through multiple Centers for Disease Control and Prevention (CDC) activities, including testing conducted across the Antimicrobial Resistance Laboratory Network, to determine whether any Enterobacterales isolates sequenced from 2017-2022 harbored Acinetobacter-associated class D carbapenemase genes. Among [~]10,000 predominantly carbapenem-resistant Enterobacterales isolates, we identified only a single Enterobacterales isolate harboring an Acinetobacter-associated class D gene - a Klebsiella pneumoniae isolate harboring a blaOXA-23-like gene. Our findings suggest that blaOXA-23-like, blaOXA-24/40-like, and blaOXA-58-like genes are rare among Enterobacterales isolates sequenced through CDC public health activities in the United States and do not warrant changes to current testing priorities at this time.

microbiology↗

bioRxiv2024

Commensal or pathogen: computational vectorizing microbial genomes for de novo risk assessment and virulence feature discovery in Klebsiella pneumoniae

Bacterial pathogenicity has traditionally focused on gene-level content with experimentally-confirmed functional properties. Hence, significant inferences are made based on similarity to known pathotypes and DNA-based genomic subtyping for risk. Herein, we achieved de novo prediction of human virulence in Klebsiella pneumoniae by expanding known virulence genes with spatially proximal gene discoveries linked by functional domain architectures across all prokaryotes. This approach identified gene ontology functions not typically associated with virulence sensu stricto. By leveraging machine learning models with these expanded discoveries, public genomes were assessed for virulence prediction using categorizations derived from isolation sources captured in available metadata. Performance for de novo strain-level virulence prediction achieved 0.81 F1-Score. Virulence predictions using expanded "discovered" functional genetic content were superior to that restricted to extant virulence database content. Additionally, this approach highlighted the incongruence in relying on traditional phylogenetic subtyping for categorical inferences. Our approach represents an improved deconstruction of genome-scale datasets for functional predictions and risk assessment intended to advance public health surveillance of emerging pathogens.

microbiology↗

bioRxiv2020

Widespread transfer of mobile antibiotic resistance genes within individual gut microbiomes revealed through bacterial Hi-C

The gut microbiome harbors a silent reservoir of antibiotic resistance (AR) genes that is thought to contribute to the emergence of multidrug-resistant pathogens through the process of horizontal gene transfer (HGT). To counteract the spread of AR genes, it is paramount to know which organisms harbor mobile AR genes and with which organisms they engage in HGT. Despite methods to characterize the bulk presence1, abundance2 and function3 of AR genes in the gut, technological limitations of short-read sequencing have precluded linking bacterial taxa to specific mobile genetic elements (MGEs) and their concomitant AR genes. Here, we apply and evaluate a high-throughput, culture-independent method for surveilling the bacterial carriage of MGEs, based on bacterial Hi-C protocols. We compare two healthy individuals with a cohort of seven neutropenic patients undergoing hematopoietic stem cell transplantation, who receive multiple courses of antibiotics throughout their prolonged hospitalizations, and are thus acutely vulnerable to the threat of multidrug-resistant infections4. We find that the networks of HGT are surprisingly distinct between individuals, yet AR and mobile genes are more dispersed across taxa within the neutropenic patients than the healthy subjects. Our data further suggest that HGT is occurring throughout the course of treatment in the microbiomes of neutropenic patients and within the guts of healthy individuals over a similar timeframe. Whereas most efforts to understand the spread of AR genes have focused on pathogenic species, our findings shed light on the role of the human gut microbiome in this process.

systems biology↗