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<p>Urinary tract infections (UTIs) caused by <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> represent a major global health burden, yet the clinical relevance of cyclomodulins and supplementary virulence genes (SVGs) in UTI pathogenesis remains largely uncharacterized. We conducted a cross-sectional study enrolling 501 patients with UTIs (82.0% outpatients; <i>E. coli</i> 73.4%, <i>K. pneumoniae</i> 26.5%) at a tertiary care center in northwestern Mexico. The prevalence of four cyclomodulin genes (<i>cnf</i>,<i> cif</i>,<i> pks</i>,<i> cdt</i>), nine SVGs, and antibiotic-resistance profiles were determined by PCR and the MicroScan WalkAway 96 system; clinical associations were evaluated using multivariate logistic regression. Overall, 22.0% of isolates carried at least one cyclomodulin gene; cnf was the most prevalent (7.7%). <i>E. coli</i> harbored cyclomodulin genes significantly more frequently than <i>K. pneumoniae</i> (25.0% vs. 13.5%; <i>p</i> = 0.006). Significant SVG co-occurrence patterns were identified: <i>papEF</i> with <i>cnf</i> or <i>pks</i>, and <i>fyuA</i> with <i>cif</i>. MDR and XDR phenotypes were detected in 22.0% and 1.0% of isolates, respectively, with markedly higher resistance in inpatient-derived strains. In-hospital mortality was 2.1%. In <i>E. coli</i>, cyclomodulin carriage was independently associated with mortality (<i>p</i> = 0.003), ICU admission (<i>p</i> = 0.048), and hospitalization (<i>p</i> = 0.003); papEF + pks co-carriage with complicated UTI (<i>p</i> = 0.002); and MDR with urinary catheter use and hospitalization. In <i>K. pneumoniae</i>, <i>cnf</i> is associated with leukocytosis and dyslipidemia; <i>pks</i> with leukocyte esterase and dyslipidemia; cyclomodulin carriage with pregnancy; and MDR with chronic kidney disease, prior surgery, and urinary catheter use. These findings establish cyclomodulins as clinically relevant virulence determinants independently associated with adverse UTI outcomes, positioning them as candidate prognostic biomarkers and potential therapeutic targets.</p>

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Cyclomodulins and supplementary virulence genes as determinants of clinical severity and antimicrobial resistance in uropathogenic Escherichia coli and Klebsiella pneumoniae

  • 期刊论文

  • 发表日期：

    2026年5月28日

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  • Jose Monroy-Higuera,
  • Uriel A. Angulo-Zamudio,
  • Nidia Leon-Sicairos,
  • Hector Flores-Villaseñor,
  • Gabriela Tapia-Pastrana,
  • Julio Medina-Serrano,
  • Adrian Canizalez-Roman

摘要

Urinary tract infections (UTIs) caused by Escherichia coli and Klebsiella pneumoniae represent a major global health burden, yet the clinical relevance of cyclomodulins and supplementary virulence genes (SVGs) in UTI pathogenesis remains largely uncharacterized. We conducted a cross-sectional study enrolling 501 patients with UTIs (82.0% outpatients; E. coli 73.4%, K. pneumoniae 26.5%) at a tertiary care center in northwestern Mexico. The prevalence of four cyclomodulin genes (cnf, cif, pks, cdt), nine SVGs, and antibiotic-resistance profiles were determined by PCR and the MicroScan WalkAway 96 system; clinical associations were evaluated using multivariate logistic regression. Overall, 22.0% of isolates carried at least one cyclomodulin gene; cnf was the most prevalent (7.7%). E. coli harbored cyclomodulin genes significantly more frequently than K. pneumoniae (25.0% vs. 13.5%; p = 0.006). Significant SVG co-occurrence patterns were identified: papEF with cnf or pks, and fyuA with cif. MDR and XDR phenotypes were detected in 22.0% and 1.0% of isolates, respectively, with markedly higher resistance in inpatient-derived strains. In-hospital mortality was 2.1%. In E. coli, cyclomodulin carriage was independently associated with mortality (p = 0.003), ICU admission (p = 0.048), and hospitalization (p = 0.003); papEF + pks co-carriage with complicated UTI (p = 0.002); and MDR with urinary catheter use and hospitalization. In K. pneumoniae, cnf is associated with leukocytosis and dyslipidemia; pks with leukocyte esterase and dyslipidemia; cyclomodulin carriage with pregnancy; and MDR with chronic kidney disease, prior surgery, and urinary catheter use. These findings establish cyclomodulins as clinically relevant virulence determinants independently associated with adverse UTI outcomes, positioning them as candidate prognostic biomarkers and potential therapeutic targets.