PDF(Pubmed)
Abstract：
Antibiotic therapy is the standard of care for urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC). However, previous antibiotic therapy may impart a selective pressure that influences the population structure and pathogenic potential of infecting UPEC strains. Here, we conducted a 3-year study using whole-genome-sequencing analysis and retrospective medical record review to characterize how antibiotic exposure influenced the phenotypic antibiotic resistance, acquired resistome, virulome, and population structure of 88 UTI-causing E. coli strains from dogs. A majority of UTI-associated E. coli strains were from phylogroup B2 and clustered within sequence type 372. Previous antibiotic exposure was associated with a population shift toward UPEC from phylogroups other than the typical urovirulent phylogroup B2. The specific virulence profiles within the accessory virulome that were associated with antibiotic use were elicited by the effect of antibiotics on UPEC phylogenetic structure. Among phylogroup B2, antibiotic exposure increased the quantity of genes within the resistome and the odds of developing reduced susceptibility to at least one antibiotic. Non-B2 UPEC strains harbored a more diverse and greater resistome that conferred reduced susceptibility to multiple antibiotic classes following antibiotic exposure. Collectively, these data suggest that previous antibiotic exposure establishes an environment that provides a selective edge to non-B2 UPEC strains through their diverse and abundant antibiotic resistance genes, despite their lack of urovirulence genes. Our findings highlight the necessity for judicious use of antibiotics as we uncover another mechanism by which antibiotic exposure and resistance can influence the dynamics of bacterial infectious disease. IMPORTANCE Urinary tract infections (UTIs) are one of the most common infections of dogs and humans. While antibiotic therapy is the standard of care for UTIs and other infections, antibiotic exposure may influence the pathogenic profile of subsequent infections. We used whole-genome sequencing and retrospective medical record review to characterize the effect of systemic antibiotic therapy on the resistance, virulence, and population structure of 88 UTI-causing UPEC strains isolated from dogs. Our results indicate that antibiotic exposure alters the population structure of infecting UPEC strains, providing a selective edge for non-B2 phylogroups that harbor diverse and abundant resistance gene catalogues but fewer urovirulence genes. These findings highlight how antibiotic resistance can influence pathogen infection dynamics and have clinical implications for the judicious use of antibiotics for bacterial infections.
摘要：
抗生素治疗是由尿路致病性大肠杆菌（UPEC）引起的尿路感染（UTI）的护理标准。然而,既往抗生素治疗可能会产生选择性压力,从而影响感染UPEC菌株的种群结构和致病潜能.这里,我们进行了一项为期3年的研究，使用全基因组测序分析和回顾性病历审查，以描述抗生素暴露如何影响表型抗生素耐药性，获得性耐药，病毒组，和来自狗的88种引起UTI的大肠杆菌菌株的种群结构。大多数UTI相关的大肠杆菌菌株来自系统群B2并且聚集在序列类型372内。先前的抗生素暴露与从典型的尿毒性系群B2以外的系群向UPEC的人口转移有关。抗生素对UPEC系统发育结构的影响引起了与抗生素使用相关的副病毒组内的特定毒力谱。在系统群B2中，抗生素暴露增加了抗性组中基因的数量，并降低了对至少一种抗生素的敏感性。非B2UPEC菌株具有更多样化和更强的耐药性，这在抗生素暴露后降低了对多种抗生素类别的敏感性。总的来说，这些数据表明，以前的抗生素暴露建立了一种环境，通过其多样化和丰富的抗生素抗性基因，为非B2UPEC菌株提供选择性优势，尽管他们缺乏尿路毒力基因.我们的发现强调了明智使用抗生素的必要性，因为我们揭示了抗生素暴露和耐药性可以影响细菌感染性疾病动态的另一种机制。重要性尿路感染（UTI）是狗和人类最常见的感染之一。虽然抗生素治疗是治疗尿路感染和其他感染的标准，抗生素暴露可能会影响后续感染的致病特征.我们使用全基因组测序和回顾性病历回顾来描述全身抗生素治疗对耐药性的影响。毒力,和从狗中分离出的88种引起UTI的UPEC菌株的种群结构。我们的结果表明，抗生素暴露改变了感染UPEC菌株的种群结构，为非B2系统组提供选择性优势，这些系统组具有多样化和丰富的抗性基因，但尿毒力基因较少。这些发现强调了抗生素耐药性如何影响病原体感染动态，并对合理使用抗生素治疗细菌感染具有临床意义。
