Biology subjects

Mendez, A. A.

Publications and source records attributed to Mendez, A. A..

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↗

bioRxiv2023

Plant Phenolics Inhibit Focal Adhesion Kinase and Suppress Host Cell Invasion by Uropathogenic Escherichia coli

Traditional folk treatments for the prevention and management of urinary tract infections (UTIs) and other infectious diseases often include plants and plant extracts that are rich in phenolic and polyphenolic compounds. These have been ascribed a variety of activities, including inhibition of bacterial interactions with host cells. Here we tested a panel of four well-studied phenolic compounds - caffeic acid phenethyl ester (CAPE), resveratrol, catechin, and epigallocatechin gallate - for effects on host cell adherence and invasion by uropathogenic Escherichia coli (UPEC). These bacteria, which are the leading cause of UTIs, can bind and subsequently invade bladder epithelial cells via an actin-dependent process. Intracellular UPEC reservoirs within the bladder are often protected from antibiotics and host defenses, and likely contribute to the development of chronic and recurrent infections. Using cell culture-based assays, we found that only resveratrol had a notable negative effect on UPEC adherence to bladder cells. However, both CAPE and resveratrol significantly inhibited UPEC entry into the host cells, coordinate with attenuated phosphorylation of the host actin regulator Focal Adhesion Kinase (FAK, or PTK2) and marked increases in the numbers of focal adhesion structures. We further show that the intravesical delivery of resveratrol inhibits UPEC infiltration of the bladder mucosa in a murine UTI model, and that resveratrol and CAPE can disrupt the ability of other invasive pathogens to enter host cells. Together, these results highlight the therapeutic potential of molecules like CAPE and resveratrol, which could be used to augment antibiotic treatments by restricting pathogen access to protective intracellular niches. IMPORTANCEUrinary tract infections (UTIs) are exceptionally common and increasingly difficult to treat due to the ongoing rise and spread of antibiotic resistant pathogens. Furthermore, the primary cause of UTIs, uropathogenic Escherichia coli (UPEC), can avoid antibiotic exposure and many host defenses by invading the epithelial cells that line the bladder surface. Here we identified two plant-derived phenolic compounds that disrupt activation of the host machinery needed for UPEC entry into bladder cells. One of these compounds (resveratrol) effectively inhibited UPEC invasion of the bladder mucosa in a mouse UTI model, and both phenolic compounds significantly reduced host cell entry by other invasive pathogens. These findings suggest that select phenolic compounds can be used to supplement existing antibacterial therapeutics by denying uropathogens shelter within host cells and tissues, and help explain some of the benefits attributed to traditional plant-based medicines.

microbiology↗