E. coli ST131 was reported from three different continents . However, recently it has become the most predominant lineage associated with variety of infections around the globe. ST131 strains have a tendency to harbor ESBL enzymes such as bla-CTX-M–15, which play a significant role in mounting resistance to β-lactam class of antibiotics . Moreover, ST131 strains show remarkable resistance to fluoroquinolones and demonstrate greater abilities to adhere bladder, kidneys and epithelial cells [4, 5]. In this study, clonal group ST131 was the most prevalent lineage, comprising 46% of the isolates and majority of these isolates (59%) belonged to the phylogenetic group B2. Prevalence of two other lineages ST405 and ST168 were 18% and 10% respectively. Involvement of these lineages in UTIs has been described earlier and recently ST405 was confirmed as an emerging uropathogenic E. coli clone in Saudi Arabia [21, 22]. Urinary tract infections caused by E. coli pose considerable challenge and are associated with high morbidity and mortality . Due to their resistance against variety of antibiotics, including β-lactams, aminoglycosides and fluoroquinolones, infections caused by pandemic clonal group ST131 are challenging to treat [23, 24]. In this context, epidemiological significance of a sub group ST131 H30-Rx has been well described [5, 25]. In this study, 50% of the ST131 strains carried H30 variant of fimH gene and 61% belonged to the serogroup O25b. Moreover, all the isolates belonging to sub-group ST131-H30-O25b carried ESBL bla-CTX-M–15 however, overall prevalence of these strains constituted 10% of the total isolates. In this study overall resistance against fluoroquinolones remained 60%, which was remarkably higher among ST131 isolates (60% vs 82%). Generally, for the treatment of UTIs commonly prescribed antibiotics include sulphamethoxazole-trimethoprim and fluoroquinolones. Due to the emerging resistance to these antibiotics alternative therapeutic choices such as nitrofurantoin, fosfomycin and β-lactam inhibitors can be used.
In this study, prevalence of ESBL genes was higher among ST131 isolates and 90% of the ST–131 isolates were resistant to ceftazidime and cefotaxime. Likewise, resistance to ceftriaxone was confirmed in 77% of these isolates. Because of their favorable safety, cephalosporins are considered important therapeutic choice for the treatment of uncomplicated UTIs among pregnant women .
Nitrofurantoin is a fluoroquinolone-sparing alternative antibiotic used for uncomplicated cystitis . In recent years use of nitrofurantoin has increased steadily, due to resistance against trimethoprim/sulfamethoxazole and aminopencillins. Contraindication of ciprofloxacin in pregnancy and adverse impact on gut flora favored the use of nitrofurantoin as a treatment option for UTIs. In this study 13% of the ST–131 isolates were resistant to nitrofurantoin.
We found that majority of the isolates belonging to the lineages ST405, ST168, ST29, ST69 and ST89 were multi-drug resistant. However, the MDR percentage was particularly higher among fluoroquinolones-resistant ST131 strains. Overall 59% of the isolates belonged to the phylogenetic group B2. A previous study from Pakistan confirmed that 50% of the UPEC isolates belonged to the phylogenetic group B2 . Interestingly however, another study conducted in Pakistan reported that only 12% of the strains belonged to phylogenetic group B2. These findings suggest that prevalence of phylogenetic group B2 may vary across different regions .
Phylogenetic group B2 strains are equipped with various VF genes related to the extra-intestinal infections. These genes include P-fimbriae, S-fimbriae, haemolysin, aerobactin, K1 and K5 antigens and capsular antigen genes [30, 31]. A previous report focusing on UPEC, in Pakistan described prevalence of various VF genes, including hlyA, sfaDE, papC,cnf1, eaeAand afaBC While another study conducted on rectal flora isolates of Pakistani children confirmed that virulence factors such as S-fimbriae, haemolysin, K–1 antigens and class III PapGadhesins are either very rare or completely absent . Among UPEC strains of phylogenetic group B2 wide range of the virulence factors including genes for adhesins (fimH 100%, papA13%, papC 47%, papEF 21% papGI 3%, papGII40%,papGIII 4%, sfa/foc14%, afa 11%, bmaE 1%), toxins (hlyA 7%, cdtB 7%) iron acquisition system (iutA 57%, feoB43%, fyuA 23%) capsular proteins (kpsMTII 26%, kpsMTIII3%) and uropathogenic specific protein (usp 14%) were detected. Moreover, we observed that gene papGIIwas significantly associated with phylogenetic group B2 strains. Association of the gene papGII with pyelonephritis and bacteraemia in human has been confirmed previously [32–34]. In the current study, fimbriae associated gene fimH was detected among 100% of the UPEC isolates consistent with previous work. Role of fimH in adhesion, invasion and formation of intracellular bacterial communities (IBCs) has been described previously and its importance in the host pathogen interaction was confirmed by higher vulnerabilities of premenopausal women to UPEC infections . Genes related to the adhesins (papEF, sfa/foc) andtoxins (hlyA) were found to be strongly associated with ST131 H30 sub-clone. Recently HlyAin interaction with natural killer (NK) cells of urinary bladder was described . Likewise, significant association of iron acquisition genes ((fyuAand feoB) was witnessed among ST131 lineage. The importance of genes related to the iron acquisition system was shown by strong upregulation of these genes during UTIs . Generally, E. coli strains causing UTI share similar properties in terms of phylogeny, sero-grouping and VF genes. Moreover, other than genetic attributes of the virulence strains host factors may play important role in the outcome of infection .