Prevalence of fosfomycin resistance in E. coli clinical isolates from UTIs remains very low. Our hypothesis was that fosfomycin resistance may be associated with a biological cost. Three groups of strains of E. coli belonging to the B2 phylogenetic group were used: clinical wild-type (WT) isolates, clinical multidrug-resistant isolates and in vitro fosfomycin-resistant derivatives from the uropathogen clinical strain E. coli CFT073. In each group fosfomycin-susceptible and -resistant isolates were compared. In vitro, we found a significantly decreased growth rate for fosfomycin-resistant strains as compared with susceptible strains in the WT group. In a murine model of ascending UTI, there was a significant reduction in infection rates with fosfomycin-resistant isolates as compared with susceptible ones, in all 3 study groups, ranging from 28 to 39% (P<0.03). All fosfomycin-susceptible clinical strains were virulent in vivo (13/13), while fosfomycin-resistant clinical strains were either virulent (2/7) or non-virulent (5/7) (P<0.002). This difference was not explained by the number of virulence factors or pathogenicity-associated islands. In conclusion, fosfomycin resistance appears to carry some biological cost in E. coli, which may explain in part the apparent paradox of the low prevalence of fosfomycin resistance despite a high rate of spontaneous mutants.

中文翻译：

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在尿道感染的鼠模型中大肠杆菌对磷霉素的耐药性的生物学成本。

来自UTI的大肠杆菌临床分离株对磷霉素的耐药率仍然很低。我们的假设是对磷霉素的耐药性可能与生物学成本有关。使用了三类属于B2系统发生组的大肠杆菌菌株：临床野生型（WT）分离株，临床多药抗性分离株和来自尿路致病菌临床菌株E. coli CFT073的体外对磷霉素的衍生物。在每组中，比较了对磷霉素敏感和耐药的菌株。在体外，我们发现抗草磷霉素的菌株的生长速率与野生型WT组相比明显降低。在所有3个研究组中，在上升性UTI的小鼠模型中，耐草磷霉素的分离株的感染率比易感株明显降低。范围从28％到39％（P <0.03）。所有对磷霉素敏感的临床菌株在体内均具有毒性（13/13），而对磷霉素耐药的临床菌株要么具有毒性（2/7），要么是无毒力（5/7）（P <0.002）。毒力因子或与致病性相关的孤岛数量无法解释这种差异。总之，磷霉素抗性似乎在大肠杆菌中带来了一些生物学代价，这可能部分解释了尽管自发突变体发生率很高，但磷霉素抗性的普遍性较低的明显悖论。