Type VI secretion system contributes to Enterohemorrhagic Escherichia coli virulence by secreting catalase against host reactive oxygen species (ROS)

Abstract

Enterohemorrhagic Escherichia coli (EHEC) is one major type of contagious and foodborne pathogens. The type VI secretion system (T6SS) has been shown to be involved in the bacterial pathogenicity and bacteria-bacteria competition. Here, we show that EHEC could secrete a novel effector KatN, a Mn-containing catalase, in a T6SS-dependent manner. Expression of katN is promoted by RpoS and OxyR and repressed by H-NS, and katN contributes to bacterial growth under oxidative stress in vitro. KatN could be secreted into host cell cytosol after EHEC is phagocytized by macrophage, which leads to decreased level of intracellular reactive oxygen species (ROS) and facilitates the intramacrophage survival of EHEC. Finally, animal model results show that the deletion mutant of T6SS was attenuated in virulence compared with the wild type strain, while the deletion mutant of katN had comparable virulence to the wild type strain. Taken together, our findings suggest that EHEC could sense oxidative stress in phagosome and decrease the host cell ROS by secreting catalase KatN to facilitate its survival in the host cells.

Insights into Klebsiella pneumoniae type VI secretion system transcriptional regulation

“…One of those mechanisms involves catalases. Curiously, OxyR regulates the expression of KatN, a catalase secreted in a T6SS-dependent manner by enterohemorrhagic E. coli [40]. OxyR is one of the regulators that induce the bacterial oxidative stress response.…”

Burkholderia cenocepacia utilizes a type VI secretion system for bacterial competition

“…These include effectors that target the peptidoglycan layer, phospholipid membrane, or host DNA/RNA, such as the amidase effector–immunity pairs termed Tae‐Tai (for type VI amidase effector/immunity; Hood et al, ; Russell et al, ; Russell et al, ; Fritsch et al, ), the type VI lipase effectors (Tle) that possess phospholipase A 1 , A 2 , or D activity (Russell et al, ), or the type VI DNase effectors (Tde; Ma et al, ), respectively. A number of anti‐eukaryotic effectors have also been described, including a P. aeruginosa effector with phospholipase D activity that can target both bacterial and eukaryotic cells (Jiang et al, ), the catalase effector, KatN, responsible for intramacrophage survival of enterohemorrhagic E. coli (Wan et al, ), and a VgrG subunit with a C‐terminal actin cross‐linking domain utilized by V. cholerae (VgrG‐1) that impairs the phagocytic activity of eukaryotic host cells (Ma, McAuley, Pukatzki, & Mekalanos, ; Pukatzki, Ma, Revel, Sturtevant, & Mekalanos, ).…”

Here, there, and everywhere: How pathogenicEscherichia colisense and respond to gastrointestinal biogeography

“…However, the CTS1 cluster was confirmed as encoding a functional T6SS (Gueguen & Cascales, ). In EHEC, the T6SS is involved in antibacterial competition and virulence towards eukaryotic hosts (B. Wan et al, ). Therefore, the use of T6SSs may be an important, and yet unexplored, mechanism by which EHEC and C. rodentium overcome colonisation resistance by the microbiota.…”