Biology subjects

Matthews, O. J.

Publications and source records attributed to Matthews, O. J..

2 recordsLinked to original sources

bioRxiv2026

The Small RNA MicC is a Multifunctional Regulator of Extraintestinal Pathogenic Escherichia coli Fitness across Multiple Host Niches

Small non-coding RNAs (sRNA) modulate diverse bacterial functions ranging from carbon metabolism to virulence gene expression. Previous research showed that the sRNA chaperone Hfq is critical for the fitness of Extraintestinal Pathogenic Escherichia coli (ExPEC), a major cause of both bloodstream and urinary tract infections (UTI). Using the reference ExPEC strain UTI89, we created deletion mutants to probe the effects of seven conserved Hfq-dependent sRNAs (DsrA, RprA, OxyS, RyhB, MicF, MicC, Spf) on resistance to oxidative stress. All of the sRNA mutants grew normally in replete lysogeny broth, but the spf and micC mutants exhibited additive effects upon challenge with reactive oxygen species generated by methyl viologen. In a murine UTI model, the spf mutant resembled the wild-type strain, whereas UTI89{Delta}micC was unable to effectively colonize the bladder despite behaving like wild type within the kidneys. This correlated with a greatly reduced ability of the micC mutant to survive within bladder epithelial cells and paralleled UTI89{Delta}micC defects in gut colonization, virulence in a sepsis model, and complement resistance. Although MicC downregulated expression of its only known target, OmpC, aberrant modulation of this porin did not entirely account for the decreased stress resistance of UTI89{Delta}micC. Rather, RNA-Seq, sRNA target predictions, and in vitro phenotypic assays revealed that MicC can impact multiple pathways linked to niche establishment, including motility, chemotaxis, and various metabolic processes. These data are consistent with MicC serving as a multifunctional regulator of ExPEC stress responses and niche-specific fitness through OmpC-dependent and - independent mechanisms. IMPORTANCEPathogenic strains of Escherichia coli are exceptionally common causes of diarrheal disease, urinary tract infection, sepsis, and meningitis. The ability of these pathogens to cause such a wide range of maladies is in part attributable to their ability to quickly adapt to and thrive within disparate and often hostile environments, including the gut, bladder, kidneys, and bloodstream. Adaptation to new environments requires rapid and precise changes in gene expression. To accomplish this feat, E. coli utilizes a suite of regulatory RNA called small RNA (sRNA). In this paper, we identified the sRNA MicC as a critical facilitator of E. coli fitness and virulence within diverse host environments via effects on the expression of multiple genes involved in bacterial motility, energy acquisition, and various other pathways. Delineating how sRNAs like MicC impact disease processes will aid the development of novel therapeutics to better combat E. coli infections.

microbiology↗

bioRxiv2025

Global Footprint of the Multidrug Resistance Island Ec17R and Resistance Gene Co-Occurrence in Pathogenic Escherichia coli Isolates

Multidrug resistant (MDR) bacterial pathogens are a major threat to global health, limiting treatment options for common infections. Extraintestinal Pathogenic Escherichia coli (ExPEC), a leading cause of bloodstream and urinary tract infections (UTIs), are often resistant to one or more antibiotic classes. Previously, we identified a clonal group of ExPEC strains (P1A) that persisted over a 5-year period from 2012 to 2016 within a female patient who suffered from frequent recurrent UTIs. A subset of these isolates carried a plasmid-borne MDR island (Ec17R) harboring 17 resistance genes. Sampling of fecal and urine samples in 2019 indicated that the patient remained colonized with the P1A lineage, including Ec17R-positive strains, over 7 years after collection of the first P1A isolates in 2012. Highlighting the public health relevance and mobility of Ec17R, we found that Ec17R-like islands are globally distributed across diverse bacterial species from various environmental, agricultural, and clinical sources, including multiple ExPEC isolates from local pediatric patients. By applying clustering approaches and Bayesian network modeling to 267 pediatric ExPEC isolates, we found that functionally distinct classes of resistance genes (including several heavy metal resistance genes) have a high probability of co-occurrence, possibly reflecting carriage within MDR islands like Ec17R. Finally, we observed that strains within the P1A lineage are recalcitrant to antibiotics for which they have no known resistance mechanisms, suggesting that these pathogens have means beyond their formidable array of resistance genes to survive within a host for years despite the administration of numerous, robust antimicrobial treatments. SIGNIFICANCEMultidrug resistance (MDR) in bacteria is a growing global health crisis that compromises our ability to treat routine infections. In this study, we investigated a clonal lineage of pathogenic Escherichia coli that persisted for many years in a patient with recurrent urinary tract infections. A subset of the E. coli strains carried by this patient possessed a large genomic island encoding resistance to multiple antibiotic classes. This MDR island is globally distributed across diverse bacterial species and niches, from clinical samples to agricultural and environmental reservoirs. Using probabilistic modeling of nearly 300 clinical isolates, we identified networks of resistance gene co-occurrence that link antibiotic and heavy metal resistance, suggesting the potential for environmental pollutants to contribute to MDR dissemination. Notably, patient-derived isolates also survived certain clinically relevant antibiotic treatments despite lacking known resistance mechanisms, highlighting tolerance and persistence as important, often overlooked drivers of therapeutic failure.

microbiology↗