Speaking the host language: how Salmonella effector proteins manipulate the host

Abstract

Salmonella injects over 40 virulence factors, termed effectors, into host cells to subvert diverse host cellular processes. Of these 40 Salmonella effectors, at least 25 have been described as mediating eukaryotic-like, biochemical post-translational modifications (PTMs) of host proteins, altering the outcome of infection. The downstream changes mediated by an effector’s enzymatic activity range from highly specific to multifunctional, and altogether their combined action impacts the function of an impressive array of host cellular processes, including signal transduction, membrane trafficking, and both innate and adaptive immune responses. Salmonella and related Gram-negative pathogens have been a rich resource for the discovery of unique enzymatic activities, expanding our understanding of host signalling networks, bacterial pathogenesis as well as basic biochemistry. In this review, we provide an up-to-date assessment of host manipulation mediated by the Salmonella type III secretion system injectosome, exploring the cellular effects of diverse effector activities with a particular focus on PTMs and the implications for infection outcomes. We also highlight activities and functions of numerous effectors that remain poorly characterized.

Specificities and redundancies in the NEL family of bacterial E3 ubiquitin ligases of Salmonella enterica serovar Typhimurium

“…Salmonella injects more than 40 effectors into host cells to manipulate their behavior and facilitate the survival and replication of the pathogen. Some of these effectors act as adaptor proteins or contribute to modifying the lipid content of host membranes, but most of these effectors exhibit some biochemical activity that mediates post-translational modifications of host proteins ( 48 ). These modifications include ubiquitination, deubiquitination, phosphorylation, dephosphorylation, hydrolysis, deamidation, glycosylation, and acetylation.…”

Salmonella infection acts as an environmental risk factor for human colon cancer

“…In S. enterica serovar Typhimurium, an extensively studied NTS, Salmonella pathogenicity islands (SPIs), SPI-1 and SPI-2, each encoding a distinct type III secretion system (T3SS), have been shown to be critical for the secretion of over 40 effector proteins into host cells (see review by Pillay et al. ( Pillay et al., 2023 )). Once Salmonella effector proteins are injected into the host cell, various host processes are modulated to facilitate Salmonella survival and replication.…”

“…While reviewing all of the studied Salmonella effector proteins is out of the scope of this mini-review, please refer to the paper by Pillay et al. for a recent review of the known NTS effector proteins ( Pillay et al., 2023 ).…”

Salmonella exploits membrane reservoirs for invasion of host cells

“…Salmonella enterica serovar Typhimurium ( S Tm) is a gram-negative intracellular bacterial pathogen that is a major cause of foodborne gastroenteritis in humans. These bacteria can rapidly invade host cells using a type 3 secretion system (T3SS) encoded by Salmonella pathogenicity Island (SPI-1) 1 . SPI-1 T3SS effectors are known to promote the delivery of membrane to the invasion site via the exocyst complex, contributing to the formation of ruffles that envelop bacteria 2 .…”

“… Salmonella utilizes a type 3 secretion system to translocate virulence proteins (effectors) into host cells during infection 1 . The effectors modulate host cell machinery to drive uptake of the bacteria into vacuoles, where they can establish an intracellular replicative niche.…”