Biology subjects

Rodriguez, A. L.

Publications and source records attributed to Rodriguez, A. L..

3 recordsLinked to original sources

bioRxiv2026

Pathogenome and Plasmid-Borne Antimicrobial Resistance Phenotypes in a Multidrug-Resistant O111:H8 Shiga Toxin-Producing Escherichia coli Strain

Plasmids contribute to virulence and antimicrobial resistance in Shiga toxin-producing Escherichia coli (STEC). Here, the mobility, gene content, and evolutionary context of four plasmids carried by an O111:H8 STEC strain designated UTAK-22: pUTAK-22.1-MDR, pUTAK-22.2-MDR, pUTAK-22.3-P1, and pUTAK-22.4-pO111 were characterized. Conjugation experiments, phenotype-based selective readouts, and comparative genomics together showed that pUTAK-22.1-MDR is self-transmissible, whereas pUTAK-22.2-MDR and pUTAK-22.4-pO111 are most consistent with mobilization in trans, making use of the strain's native helper plasmid background, while pUTAK-22.3-P1 represents a conjugation-deficient IncY phage-derived replicon. Genome annotation and comparative analyses further highlighted the structural diversity and mosaic composition of these plasmids, including P1-like phage remnants, virulence loci, and distinct antimicrobial resistance modules. Phenotypic profiling of the native wild-type plasmid complement and selected transconjugants in the recipient E. coli strain WG5 further showed that the presence of co-resident plasmids and redundant resistance determinants results in dosage-dependent streptomycin tolerance. Together, these findings expand our understanding of the mobility landscape, evolutionary dynamics, and resistance potential of STEC plasmids, while underscoring the importance of interpreting resistance phenotypes in the context of a strain's natural plasmid composition.

microbiology↗

bioRxiv2026

Transmembrane Domain Dominance Drives Emergent Signaling and Allosteric Inversion in mGlu1/5 Heterodimers

Class C GPCRs function as obligate dimers in which only one G protein can engage the complex at a time, but how each protomer contributes to heterodimer coupling has remained unresolved. Using CODA-RET, a BRET-based assay reporting direct Gq recruitment to defined, full-length receptor pairs, we show that signaling at the mGlu/ heterodimer flows predominantly through the mGlu protomer; domain-swapped chimeras localize this dominance to the transmembrane domain. The dominance generates emergent signaling: cis-acting mGlu PAMs and NAMs undergo allosteric inversion when coupling is restricted to mGlu. By contrast, the mGlu-selective NAM MTEP is silent at the heterodimer, mirroring mGlus minimal role in driving Gq. Because the mGlu PAM tested acts only in cis, a trans-acting mGlu PAM would theoretically be selective for mGlu/ homomers. These findings open a pharmacological design space in which protomer target and cis-versus-trans mode of action tune selectivity across mGlu/, mGlu/, and mGlu/ dimers.

neuroscience↗

bioRxiv2025

Phylogenomic framework and virulence gene boundaries of emerging Shiga toxin producing Escherichia coli O118 informed by the comprehensive profiling of 359 O118 genomes

Non-O157 Shiga toxin-producing Escherichia coli (STEC), particularly the O118 serogroup, are emerging pathogens linked to severe foodborne illnesses, including hemolytic uremic syndrome. The hallmark of STEC virulence is the production of a potent phage-borne cytotoxin, often accompanied by the locus of enterocyte effacement (LEE). This study explores the genomic landscape, virulence factors, and resistance traits of O118 STEC. We analyzed 357 publicly available O118 genomes across ten H-antigens and included two clinically significant O118:H16 STEC strains sequenced to closure. Pangenome assessment and core genome multilocus sequence typing (MLST) based on 4,160 shared genes revealed phylogenetic clustering by H-type and delineated distinct STEC-phylogroups, alongside relationships to non-STEC pathovars such as uropathogenic E. coli (UPEC), enteropathogenic E. coli (EPEC), and enterotoxigenic E. coli (ETEC). Identified STEC phylogroups encompassed H6, H12, H16, and H2 strains with diverse Shiga toxin (stx) profiles (stx1a, stx2a, stx2b, stx2c, stx2f). A subset of H2-STEC lacked stx, suggesting potential secondary phage loss. Most STEC groups harbored the locus of enterocyte effacement (LEE). Further, a strong correlation was observed between H-antigens and eae subtypes, with specific pairings such as H6/eae-{iota}, H16/eae-{beta}, and H2/eae-{varepsilon}. Horizontally acquired pathogenicity islands--including O-island 122 in H16 strains and a novel pathogenicity-associated island carrying antibiotic resistance--along with other loci related to colonization and interbacterial competition, further enhance these strains virulence potential. Our findings underscore the genetic diversity and virulence potential of O118 STEC. Understanding phylogroup-specific traits and resistance markers is crucial for effective surveillance and public health interventions. ImportanceShiga toxin-producing Escherichia coli (STEC) are a major public health concern, responsible for illnesses ranging from diarrhea to life-threatening kidney damage. Among non-O157 STEC, serogroup O118 is increasingly recognized as an emerging STEC lineage. This study provides the most comprehensive genomic analysis to date of O118 STEC, offering critical insights into their pathogenome, virulence traits, and antimicrobial resistance inventories. Notably, we identified a novel 74 kb pathogenicity island in clinical strain H16-12089 that encodes a combination of multidrug resistance genes, virulence factors, and interbacterial competition systems. Understanding the genetic makeup and virulence potential of these pathogens is essential for improving surveillance, risk assessment, and public health interventions.

genomics↗