Rodrigues Inês C, Ribeiro-Almeida Marisa, Campos Joana, Silveira Leonor, Leite-Martins Liliana, Ribeiro Jorge, Martins da Costa Paula, Prata Joana C, Pista Ângela, Martins da Costa Paulo
School of Medicine and Biomedical Sciences, University of Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), Terminal de Cruzeiros do Porto, de Leixões, Av. General Norton de Matos s/n, 4450-208 Matosinhos, Portugal.
Microorganisms. 2025 Aug 20;13(8):1946. doi: 10.3390/microorganisms13081946.
Recurrent urinary tract infections (UTIs) pose a significant clinical challenge in both human and veterinary medicine, due to antibiotic-resistant and biofilm-forming bacteria. We hypothesized that high glucose levels in diabetic animals enhance biofilm formation and reduce antibiotic efficacy, promoting infection persistence. This study analyzed from a diabetic female Labrador Retriever with recurrent UTIs over 18 months, focusing on antimicrobial resistance, biofilm-forming capacity, and genomic characterization. Most isolates (9/11) were resistant to ampicillin and fluoroquinolones. Whole genome sequencing of six selected isolates revealed that they belonged to the multidrug-resistant ST1193 lineage, a globally emerging clone associated with persistent infections. Phylogenetic analysis revealed clonal continuity across six UTI episodes, with two distinct clones identified: one during a coinfection in the second episode and another in the last episode. High-glucose conditions significantly enhanced biofilm production and dramatically reduced antibiotic susceptibility, as evidenced by a marked increase in minimum biofilm inhibitory concentrations (MBICs), which were at least 256-fold higher than the corresponding minimum inhibitory concentration (MIC). Sulfamethoxazole-trimethoprim demonstrated the strongest antibiofilm activity, though this was attenuated in glucose-supplemented environments. This research highlights the clinical relevance of glucosuria in diabetic patients and emphasizes the need for therapeutic strategies targeting biofilm-mediated antibiotic tolerance to improve the management of recurrent UTIs.
复发性尿路感染（UTIs）在人类和兽医学中都构成了重大的临床挑战，这是由于存在抗生素耐药性和形成生物膜的细菌。我们假设糖尿病动物体内的高血糖水平会增强生物膜的形成并降低抗生素疗效，从而促使感染持续存在。本研究分析了一只患有复发性UTIs的糖尿病雌性拉布拉多猎犬在18个月内的情况，重点关注抗菌药物耐药性、生物膜形成能力和基因组特征。大多数分离株（9/11）对氨苄青霉素和氟喹诺酮类耐药。对六个选定分离株的全基因组测序显示，它们属于多重耐药的ST1193谱系，这是一个与持续性感染相关的全球新兴克隆。系统发育分析揭示了六个UTI发作之间的克隆连续性，鉴定出两个不同的克隆：一个在第二次发作的合并感染期间，另一个在最后一次发作中。高糖条件显著增强了生物膜的产生，并显著降低了抗生素敏感性，最低生物膜抑制浓度（MBICs）显著增加就是证明，MBICs比相应的最低抑菌浓度（MIC）至少高256倍。磺胺甲恶唑-甲氧苄啶表现出最强的抗生物膜活性，不过在补充葡萄糖的环境中这种活性会减弱。这项研究突出了糖尿病患者中糖尿的临床相关性，并强调需要针对生物膜介导的抗生素耐受性的治疗策略，以改善复发性UTIs的管理。
