Quinolone-and fluoroquinolone-resistant Escherichia coli strains harbor fewer virulence factors than susceptible strains. The reasons underlying this correlation are incompletely understood. We investigated the phylogenetic background, the presence of the papC, hlyA, and cnf1 (pathogenicity island II J96 -associated), fimA, iss, and iutA genes, and the presence of type 1 fimbriae, P fimbriae, and hemolysin in 243 urinary E. coli isolates resistant only to quinolones (8%), resistant to both quinolones and fluoroquinolones (51%), or susceptible to both drugs (41%). Group B2 accounted for 56% of the isolates, showing a significantly higher prevalence among fluoroquinolone-susceptible strains than among resistant strains (65% versus 50% [P ؍ 0.03]). hly and cnf1 were significantly more associated with susceptibility (P < 0.001) and with group B2 (P < 0.001 for group B2 versus groups A and D). However, within group B2, fluoroquinolone-resistant strains showed lower prevalences of papC, hlyA, and cnf1 than their susceptible counterparts (P < 0.001). In contrast, the incidence of iutA appeared higher for refractory isolates, including group B2, than for susceptible isolates (P < 0.001). Only in group B2 did fluoroquinolone-resistant strains reveal a lesser ability to agglutinate Saccharomyces cerevisiae (7%) than quinolone-resistant (87%) and susceptible (80%) isolates, despite uniform possession of fimA genes. No similar contrast emerged for expression of hemolysin and P fimbriae. Mutations conferring quinolone and fluoroquinolone resistance may thus require a particular genetic background, not strictly correlated with phylogenetic groups. More interestingly, the mutational event itself can affect the expression of type 1 fimbriae, at least in the prevalent and complex B2 strains.Urinary tract infections (UTIs) in humans are the most frequent bacterial disease, affecting both inpatients and outpatients. Especially the uncomplicated cases are mainly due to extraintestinal pathogenic Escherichia coli (ExPEC) (39). In recent years, management of UTIs has become increasingly problematic due to the emergence of resistance to first-line antibiotics among the causative bacteria, particularly among uropathogenic E. coli (UPEC) strains. This phenomenon involves quinolones (Q) and fluoroquinolones (FQ) (25), drugs of paramount importance in the treatment of several other infectious diseases. Indeed, the renal excretion of these molecules and the availability of oral and parenteral formulations have allowed them to compete with aminoglycosides and betalactams in the therapy of complicated UTIs, especially in the hospital setting. Their appropriate spectrum and good tolerability have also led to increased empirical adoption in uncomplicated infections, although their usage for these conditions in outpatients is still under debate.In E. coli, as in other gram-negative bacteria, DNA gyrase, which codifies type II DNA topoisomerases, is the main target of Q and FQ, and mutation in gyrA is the most common way to acquire resistance....