Role of uropathogenic Escherichia coli outer membrane protein T in pathogenesis of urinary tract infection

He, Xiwei; Wang, Qin; Peng, Liang; Qu, Yarong; Puthiyakunnon, Santhosh; Liu, Xiaolu; Hui, Chang Ye; Boddu, Swapna; Cao, Hong; Huang, Sheng‐He

doi:10.1093/femspd/ftv006

Cited by 27 publications

(26 citation statements)

References 42 publications

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“…Detection of specific genes, including ompT , is often used to characterize virulent clinical UPEC isolates (Johnson et al, ; Najafi et al, ). Previous studies have suggested that OmpT from the UPEC strain CFT073 is involved in adhesion, invasion, and/or inactivation of AMPs (Brannon et al, ; He et al, ). While the presence of ompT is associated with virulent strains, its precise contribution remains unclear, as UPEC clinical isolates have highly variable genetic sequences (Schreiber et al, ).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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“…In mouse urinary tract infection (UTI) models, following adhesion and internalization within bladder umbrella epithelial cells, UPEC can escape the endocytic vesicle and proliferate in the cytoplasm as intracellular bacterial communities (IBCs; Anderson et al, 2003). The presence of IBCs has been corroborated by numerous laboratories using a variety of mouse strains and UPEC isolates (Garofalo et al, 2007;He et al, 2015;Nicholson, Watts, & Hunstad, 2009;Wieser, Guggenberger, Pritsch, Heesemann, & Schubert, 2011). Isolation of IBCs from human UTI patients further establishes the physiological relevance of this intracellular growth phase (Rosen, Hooton, Stamm, Humphrey, & Hultgren, 2007;Scott, Haake, Churchill, Justice, & Kim, 2015).…”

Section: Introductionmentioning

confidence: 94%

Matrix stiffness regulates endosomal escape of uropathogenicE. coli

Moorthy

Byfield

Janmey

et al. 2020

Cellular Microbiology

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Uropathogenic E. coli (UPEC) infection in vivo is characterized by invasion of bladder umbrella epithelial cells followed by endosomal escape and proliferation in the cytoplasm to form intracellular bacterial communities. By contrast, UPEC infection in tissue culture models results in bacteria being trapped within Lamp1‐positive endosomes where proliferation is limited. Pharmacological disruption of the actin cytoskeleton has been shown to facilitate UPEC endosomal escape in vitro and extracellular matrix stiffness is a well‐characterized physiological regulator of actin dynamics; therefore, we hypothesized that substrate stiffness may play a role in UPEC endosomal escape. Using functionalized polyacrylamide substrates, we found that at physiological stiffness, UPEC escaped the endosome and proliferated rapidly in the cytoplasm of bladder epithelial cells. Dissection of the cytoskeletal signaling pathway demonstrated that inhibition of the Rho GTPase RhoB or its effector PRK1 was sufficient to increase cytoplasmic bacterial growth and that RhoB protein level was significantly reduced at physiological stiffness. Our data suggest that tissue stiffness is a critical regulator of intracellular bacterial growth. Due to the ease of doing genetic and pharmacological manipulations in cell culture, this model system may provide a useful tool for performing mechanistic studies on the intracellular life cycle of uropathogens.

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“…The latter include Afa/Dr adhesins, E. coli common pili, Fml pili, flagella, Outer membrane protein T (OmpT), the salmochelin siderophore receptor IroN, and the Rho GTPase-activating toxin Cytotoxic Necrotizing Factor 1 (CNF1) (see Fig. 4A) (101–111). The specific sets of bacterial and host factors that are engaged by UPEC to gain access to intracellular niches likely vary as the pathogens encounter changing environments and host cell types during the course of a UTI.…”

Section: Mechanisms Of Bladder Cell Invasion By Upecmentioning

confidence: 99%

Invasion of Host Cells and Tissues by Uropathogenic Bacteria

2016

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Within the mammalian urinary tract uropathogenic bacteria face many challenges, including the shearing flow of urine, numerous antibacterial molecules, the bactericidal effects of phagocytes, and a scarcity of nutrients. These problems may be circumvented in part by the ability of uropathogenic Escherichia coli (UPEC) and several other uropathogens to invade the epithelial cells that line the urinary tract. By entering host cells, uropathogens can gain access to additional nutrients and protection from both host defenses and antibiotic treatments. Translocation through host cells can facilitate bacterial dissemination within the urinary tract, while the establishment of stable intracellular bacterial populations may create reservoirs for relapsing and chronic urinary tract infections (UTIs). Here we review the mechanisms and consequences of host cell invasion by uropathogenic bacteria, with consideration of the defenses that are brought to bear against facultative intracellular pathogens within the urinary tract. The relevance of host cell invasion to the pathogenesis of UTIs in human patients is also assessed, along with some of the emerging treatment options that build upon our growing understanding of the infectious life cycle of UPEC and other uropathogenic bacteria.

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Role of uropathogenic Escherichia coli outer membrane protein T in pathogenesis of urinary tract infection

Cited by 27 publications

References 42 publications

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

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

Matrix stiffness regulates endosomal escape of uropathogenicE. coli

Invasion of Host Cells and Tissues by Uropathogenic Bacteria

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