PSEUDOMONAS aeruginosa, a leading cause of microbial keratitis, continues to challenge clinicians with rising antimicrobial resistance. A recent study underscores critical differences in resistance patterns between P. aeruginosa strains harboring either the exoU or exoS toxin genes, variations that could influence treatment outcomes.
Analyzing 187 clinical isolates from microbial keratitis cases, researchers identified the presence of exoU or exoS genes using PCR and evaluated resistance to key antibiotics, including ciprofloxacin, levofloxacin, gentamicin, and tobramycin. Their findings revealed that exoU-positive strains consistently exhibited higher antimicrobial resistance than their exoS counterparts. Specifically, resistance rates for exoU strains reached 38.2% for ciprofloxacin compared to 20.5% for exoS strains, 29.1% vs. 12.1% for levofloxacin, 40% vs. 23.5% for gentamicin, and 29.1% vs. 14.4% for tobramycin (all p < 0.05). Whole genome sequencing of 39 isolates further uncovered a higher prevalence of resistance-related mutations in exoU strains. Notably, mutations in DNA gyrase (GyrA Thr83Ile) and topoisomerase IV (ParC Ser87Ile), both associated with fluoroquinolone resistance, were exclusive to exoU isolates. In addition, exoU strains showed alterations in efflux pump regulators such as MexZ (Gly89Ser), NalC (Asp79Glu), and MexS (Val73Ala), enhancing their ability to expel antibiotics and evade treatment. Acquired resistance genes were also disproportionately present in exoU strains, with aph(6)-Id detected in 55% and aph(3'')-Ib in 60%, compared to 0% and 5.3% respectively in exoS isolates (p < 0.01). Furthermore, mutations in DNA repair genes mutL and mutS, which can drive genomic instability and resistance development, were significantly more common in exoU strains. These findings suggest that the exoU gene not only confers virulence but is also linked to a greater arsenal of resistance mechanisms, particularly against fluoroquinolones and aminoglycosides. Understanding these genetic distinctions could inform tailored antimicrobial strategies for treating P. aeruginosa infections, especially in vision-threatening cases of microbial keratitis. Reference: Abdelraouf K et al. Differences in antimicrobial resistance between exoU and exoS isolates of Pseudomonas aeruginosa. Eye Contact Lens. 2024;50(4):181-187.
