Identification and characterization of OmpT‐like proteases in uropathogenic Escherichia coli clinical isolates

Abstract

Bacterial colonization of the urogenital tract is limited by innate defenses, including the production of antimicrobial peptides (AMPs). Uropathogenic Escherichia coli (UPEC) resist AMP‐killing to cause a range of urinary tract infections (UTIs) including asymptomatic bacteriuria, cystitis, pyelonephritis, and sepsis. UPEC strains have high genomic diversity and encode numerous virulence factors that differentiate them from non‐UTI‐causing strains, including ompT. As OmpT homologs cleave and inactivate AMPs, we hypothesized that UPEC strains from patients with symptomatic UTIs have high OmpT protease activity. Therefore, we measured OmpT activity in 58 clinical E. coli isolates. While heterogeneous OmpT activities were observed, OmpT activity was significantly greater in UPEC strains isolated from patients with symptomatic infections. Unexpectedly, UPEC strains exhibiting the greatest protease activities harbored an additional ompT‐like gene called arlC (ompTp). The presence of two OmpT‐like proteases in some UPEC isolates led us to compare the substrate specificities of OmpT‐like proteases found in E. coli. While all three cleaved AMPs, cleavage efficiency varied on the basis of AMP size and secondary structure. Our findings suggest the presence of ArlC and OmpT in the same UPEC isolate may confer a fitness advantage by expanding the range of target substrates.

Genetic Determinants of Resistance to Extended-Spectrum Cephalosporin and Fluoroquinolone in Escherichia coli Isolated from Diseased Pigs in the United States

“…Similarly, hlyF (hemolysin), iutA (iron uptake), and ompT (outer membrane protease) genes present on some of the bla CTX-M -IncF plasmids are very commonly found in avian pathogenic E. coli ( 75 ). iucC (aerobactin synthesis), iutA , and ompT genes also play key roles in the pathogenesis of severe extraintestinal infections in humans ( 76 – 78 ). The presence of virulence factors and antimicrobial resistance genes on epidemic IncF plasmids have previously contributed to global domination of E. coli ST131 clones ( 30 ) and can potentially aid in the successful dissemination of emerging E. coli lineages identified in this study.…”

An Introduction to Bacterial Biofilms and Their Proteases, and Their Roles in Host Infection and Immune Evasion

“…However, the most virulent UPEC strains encode not only for OmpT but also for an OmpT-like protease called ArlC. Additionally, in combination, these strains can degrade and inactivate a much wider selection of AMPs [ 97 ]. In Salmonella enterica , the outer membrane aspartyl peptidase PgtE, which exhibits a 46% sequence identity with E. coli OmpT, confers resistance against the antimicrobial peptides C18G and LL-37 [ 98 ].…”

The Potential of Human Peptide LL-37 as an Antimicrobial and Anti-Biofilm Agent

“…EHEC can cleave LL-37 at dibasic sequences, leading to proteolytic fragments that lack all antimicrobial activity [65], whereas the low OmpT levels in UPEC also does not contribute as significantly to LL-37 resistance [25]. That being said, if UPEC strains with high protease activity have the ompT-like gene arlC along with the ompT gene, there is an associated fitness advantage [66]. The arlC has also been implicated in resistance to CAMPs in the Adherent-invasive E. coli (AIEC) phenotype [67].…”