**13. Antimicrobial drugs and uropathogenic** *Escherichia coli*

*E. coli* are mainly associated with phylogenetic groups A or B1, and are mainly devoid of virulence determinants [118, 120, 121]. The overlapping associations of VFs and phylogeny with clinical virulence makes it difficult to understand which directly determines virulence. However, some studies in children showed that pyelonephritis isolates more often belonged to group B2, contained on average higher prevalences of individual VF genes, and consequently had higher VF scores than did cystitis or fecal isolates, suggesting that both VF repertoire and

UTI syndrome-specific differences among *E. coli* clinical and fecal isolates from men are consistent with findings from women, which have shown a gradient of virulence from *E. coli* strains causing more invasive UTI syndromes, such as pyelonephritis and febrile UTI, through those causing cystitis, to fecal strains [9, 122]. However, men are less likely than women or girls, to develop cystitis due to low-virulence strains, which is consistent with a previous observation that isolates from men with febrile UTI appeared relatively virulent, even in the

In most patient groups, pyelonephritis isolates tend to exhibit the highest prevalences of many individual VFs, have the highest VF scores, and are the most likely to belong to phylogenetic group B2, ST131, and a UTI-associated O type. The reported higher prevalence of pap operon genes (encoding P fimbriae) in pyelonephritis than cystitis isolates correlates with increased tropism for the kidney of P fimbriated strains [121, 123]. papGII has been shown, experimentally, to contribute to pathogenesis of pyelonephritis [124, 125], and OmpT is strongly associated with febrile UTI in men [122, 126]. However, it is not clear whether these VFs act individually or in concert with other known or unknown VFs in causing pyelonephritis.

In men and women, although cystitis and pyelonephritis isolates differ in inferred molecular virulence, phylogenetic group distribution is similar between the two clinical syndromes. However, within each phylogenetic group, VF scores exhibit a gradient across source groups (fecal < cystitis < pyelonephritis), suggesting the presence of different virulence strata within each phylogenetic group, with more virulent strains selectively causing pyelonephritis and less virulent strains being associated with cystitis and fecal isolates in that order. This suggests that VF repertoire is as, or more, important than phylogenetic background for predicting

Although cystitis and pyelonephritis isolates differ significantly in inferred virulence in various patient groups, no single VF profile is unique to any clinical syndrome or patient group, implying that UTI pathogenesis is multiply determined, as suggested by several previous studies [122, 128]. Thus, intervention strategies based on VF genes might have to involve multiple targets, which would offer the extra advantage of protection against a wide range

The genes encoding specific UPEC VFs can be exclusively chromosomal (e.g., *pap* and *hly*); exclusively or principally plasmid-associated (e.g., *iss* and *traT*); or can occur in either location

phylogenetic background play important roles in UTI pathogenesis.

54 *Escherichia coli* Escherichia coli - Recent Advances on Physiology, Pathogenesis and Biotechnological Applications - Recent Advances on Physiology, Pathogenesis and Biotechnological Applications

presence of host compromise [122].

pathogenic behavior in UPEC [122, 127].

of UTI syndromes.

**12. Transmission of VFs**

Managing UTI caused by UPEC has become challenging over the years due to increasing resistance to the commonly used antibiotics [135–139], which poses a great threat to future capacity to treat UTI caused by UPEC. Although TMP-SMX has traditionally been used as a first-line treatment for UTI [140], there are reports of increased resistance to this antibiotic, which in some countries is in the range 15–20% [137]. Many UPEC strains resistant to TMP-SMZ are also resistant to amoxicillin and cephalexin. Nitrofurantoin remains highly effective against UPEC, but is mainly used for cystitis treatment due to its inability to attain sufficient serum levels to treat invasive or systemic infections [137], and all have excellent bioavailability and achieve high urinary concentrations. However, increased FQ use has resulted in a rise in the prevalence of resistance, and FQ-resistant *E. coli* has become a major problem in several countries [141].
