EnterohemorrhagicEscherichia coliOmpT regulates outer membrane vesicle biogenesis

Abstract

Enterohemorrhagic Escherichia coli (EHEC) infection from food or water often results in severe diarrheal disease and is a leading cause of death globally. Outer membrane vesicles (OMVs) secreted from E. coli induce lethality in mice. The omptin outer membrane protease OmpT from E. coli inactivates antimicrobial peptides and may enhance colonization of the uroepithelium, but its precise function remains unclear. Given OmpT is an outer membrane protease, we hypothesized it may have a role in OMV biogenesis. To further characterize the effect of OmpT on OMV production, a genetic approach using wild type, an ompT deletion mutant and an ompT overexpressing construct in EHEC were employed. ompT gene deletion markedly decreased OMV production and stainable lipid but increased vesicle diameter. Conversely, ompT overexpression profoundly increased OMV biogenesis but decreased stainable lipid, protein content, and vesicle diameter. Alterations in EHEC ompT gene expression have an impact on the biogenesis, composition, and size of OMVs. Changes in ompT gene expression may dynamically alter OMV formation, composition, and diameter in response to different host environments and contribute to cell-free intercellular communication to enhance bacterial growth and survival.

EnterohemorrhagicEscherichia coliHybrid Pathotype O80:H2 as a New Therapeutic Challenge

“…The minimal combination of plasmidic genes common to all strains was the association of ompT p and hlyF , which might represent a beneficial influence on the intestinal pathogenic virulence of E. coli O80:H2 . Chromosomal ompT and hlyF are involved in the secretion of outer membrane vesicles, which might serve as transporters of toxins and thus might boost the virulence of Stx-producing E. coli ( 30 , 31 ). Whether ompT p has a similar role remains to be further investigated.…”

Immunoproteomic Analysis To Identify Shiga Toxin-Producing Escherichia coli Outer Membrane Proteins Expressed during Human Infection

“…Therefore, OmpT could play a defensive role against the host's immune response. Moreover, a role for OmpT in outer membrane vesicle (OMV) biogenesis in STEC has been described recently (86). The ompT gene is abundant and widely distributed in E. coli.…”

Enterohaemorrhagic Escherichia coli produces outer membrane vesicles as an active defence system against antimicrobial peptide LL-37

“…Recently, Premjani et al (2014) reported that production of OMVs by EHEC was decreased upon ompT gene deletion and enhanced by overexpression of the ompT gene. On the basis of these results, it was proposed that changes in ompT gene expression positively affect the formation of OMVs in response to changes in the environment.…”

“…OMVs are derived from the outer membrane and include mainly materials from the outer membrane and periplasm. In addition, although precise mechanisms remain unknown, gene products that positively affect OMVs production have been reported, such as HlyF of extraintestinal pathogenic E. coli and OmpT of EHEC (Murase et al, 2016;Premjani, Tilley, Gruenheid, Le Moual, & Samis, 2014). In addition, OMVs has been shown to deliver virulence factors to host cells (Jager, Keese, Roessle, Steinert, & Schromm, 2015;Rompikuntal et al, 2015).…”

“…OMVs have been shown to have diverse functions that promote bacterial survival, including the removal of misfolded proteins, nutrient acquisition, transfer of antibiotic resistance, biofilm development, absorption of AMPs and phages, and pathogenesis . Deletion of the ompT gene in EHEC markedly decreases the production of OMVs and changes vesicle size (Premjani et al, 2014). The production of OMVs is affected by a variety of proteins, which are involved in cross-linking between the outer membrane and peptidoglycan, lipopolysaccharide (LPS) synthesis and remodelling, and oxidative stress (Elhenawy et al, 2016;Kulp et al, 2015;Schwechheimer, Rodriguez, & Kuehn, 2015).…”