Correlation Between Antimicrobial Resistance, Virulence Determinants and Biofilm Formation Ability Among Extraintestinal Pathogenic Escherichia coli Strains Isolated in Catalonia, Spain

Abstract

Escherichia coli is a well-characterized bacterium highly prevalent in the human intestinal tract and the cause of many important infections. The aim of this study was to characterize 376 extraintestinal pathogenic E. coli strains collected from four hospitals in Catalonia (Spain) between 2016 and 2017 in terms of antimicrobial resistance, siderophore production, phylogroup classification, and the presence of selected virulence and antimicrobial resistance genes. In addition, the association between these characteristics and the ability to form biofilms was also analyzed. The strains studied were classified into four groups according to their biofilm formation ability: non-biofilm formers (15.7%), weak (23.1%), moderate (35.6%), and strong biofilm formers (25.6%). The strains were highly resistant to ciprofloxacin (48.7%), trimethoprim-sulfamethoxazole (47.9%), and ampicillin (38%), showing a correlation between higher resistance to ciprofloxacin and lower biofilm production. Seventy-three strains (19.4%) were ESBL-producers. However, no relationship between the presence of ESBL and biofilm formation was found. The virulence factor genes fimH (92%), pgaA (84.6%), and irp1 (77.1%) were the most prevalent in all the studied strains. A statistically significant correlation was found between biofilm formation and the presence of iroN, papA, fimH, sfa, cnf, hlyA, iutA, and colibactin-encoding genes clbA, clbB, clbN, and clbQ. Interestingly, a high prevalence of colibactin-encoding genes (19.9%) was observed. Colibactin is a virulence factor, which interferes with the eukaryotic cell cycle and has been associated with colorectal cancer in humans. Most colibactin-encoding E. coli isolates belonged to phylogroup B2, exhibited low antimicrobial resistance but moderate or high biofilm-forming ability, and were significantly associated with most of the virulence factor genes tested. Additionally, the analysis of their clonal relatedness by PFGE showed 48 different clusters, indicating a high clonal diversity among the colibactin-positive strains. Several studies have correlated the pathogenicity of E. coli and the presence of virulence factor genes; however, colibactin and its relationship to biofilm formation have been scarcely investigated. The increasing prevalence of colibactin in E. coli and other Enterobacteriaceae and the recently described correlation with biofilm formation, makes colibactin a promising therapeutic target to prevent biofilm formation and its associated adverse effects.

Effects of Polyphosphate metabolism Mutations on Biofilm, Capsule Formation and Virulence Traits in Hypervirulent ST23Klebsiella pneumoniaeSGH10

“…However, this explanation does not fully account for the increased proteins from the fim operon, indicating the involvement of broader regulatory mechanisms. A recent study has reported a direct correlation between biofilm formation and the colibactin operon in isolates of E. coli and K. pneumoniae 71,72 . Furthermore, since it has been demonstrated that the inactivation of PPK by mutagenesis reduces the promoter activity of clbB (the gene that encodes for an essential enzyme for colistin biosynthesis) and decreases the production level of colibactin 73 , it is possible that the absence of this enzyme also leads to a decrease in biofilm formation through this pathway.…”

Inorganic Polyphosphate Affects Biofilm Assembly, Capsule Formation, and Virulence of Hypervirulent ST23 Klebsiella pneumoniae

“…coli and K. pneumoniae. , Furthermore, since it has been demonstrated that the inactivation of PPK by mutagenesis reduces the promoter activity of clbB (the gene that encodes for an essential enzyme for colistin biosynthesis) and decreases the production level of colibactin, it is possible that the absence of this enzyme also leads to a decrease in biofilm formation through this pathway. Recently, a phenotypic switch between type III fimbriae and the hypermucoviscous capsule in response to iron levels has been reported in the SGH10 strain. , The iron-regulated outer membrane protein IroP, encoded in the virulence plasmid, inhibits the expression of the mrk operon under low iron conditions, inhibiting biofilm formation.…”

“…A recent study has reported a direct correlation between biofilm formation and the colibactin operon in isolates of E. coli and K. pneumoniae. 64,65 Furthermore, since it has been demonstrated that the inactivation of PPK by mutagenesis reduces the promoter activity of clbB (the gene that encodes for an essential enzyme for colistin biosynthesis) and decreases the production level of colibactin, 66 it is possible that the absence of this enzyme also leads to a decrease in biofilm formation through this pathway. Recently, a phenotypic switch between type III fimbriae and the hypermucoviscous capsule in response to iron levels has been reported in the SGH10 strain.…”

Correlation between antimicrobial resistance, biofilm formation, and virulence determinants in uropathogenic Escherichia coli from Egyptian hospital

“…The biofilm formation capacity of the isolates was evaluated using the 96-well microtiter plate assay as previously described [ 17 ]. In short, bacterial suspensions in Luria Bertani (LB) broth were incubated at 37 °C for 18–24 h with shaking.…”

“…Extensive research on the relationship between antimicrobial resistance and biofilm formation capacity has produced contradictory findings. It was reported that biofilm formation enhances bacterial resistance by several mechanisms, such as reduced antimicrobial diffusion and delayed growth rates [ 13 , 17 ]. Conversely, other studies suggested that antimicrobial resistance bears a considerable fitness cost on bacterial cells, which may reduce their biofilm formation ability.…”