Envelope stress responses defend against type six secretion system attacks independently of immunity proteins

Abstract

The arms race among microbes is a key driver in the evolution of not only the weapons but also defence mechanisms. Many gram-negative bacteria use the type six secretion system (T6SS) to deliver toxic effectors directly into neighbouring cells. Defence against effectors requires cognate immunity proteins. However, here we show immunity-independent protection mediated by envelope stress responses in Escherichia coli and Vibrio cholerae against a V. cholerae T6SS effector, TseH. We demonstrate that TseH is a PAAR-dependent species-specific effector highly potent against Aeromonas species but not against its V. cholerae immunity mutant or E. coli . Structural analysis reveals TseH is likely a NlpC/P60 family cysteine endopeptidase. We determine that two envelope stress response pathways, Rcs and BaeSR, protect E. coli from TseH toxicity by mechanisms including capsule synthesis. The two-component system WigKR (VxrAB) is critical for protecting V. cholerae from its own T6SS despite expressing immunity genes. WigR also regulates T6SS expression, suggesting a dual role in attack and defence. This deepens our understanding of how bacteria survive T6SS attacks and suggests that defending against the T6SS represents a major selective pressure driving the evolution of species-specific effectors and protective mechanisms mediated by envelope stress responses and capsule synthesis.

Role of Recipient Susceptibility Factors During Contact-Dependent Interbacterial Competition

“…Besides RS factors, recent studies have revealed the presence of immunity-independent resistance in recipient cell that were nicely reviewed by Robitaille et al (2020). These recipient defense factors or mechanisms include physical barriers such as exopolysaccharide (Toska et al, 2018), envelope stress responses (Hersch et al, 2020), or peptidoglycan editing (Le et al, 2020). Growing evidence of the involvement of recipient factors in either enhancing T6SS toxicity or defense against T6SS indicates an evolutionary arms race during interbacterial competition, which may play roles in shaping microbiome.…”

Capsule Protects Acinetobacter baumannii From Inter-Bacterial Competition Mediated by CdiA Toxin

“…A recent publication described that E. coli and Vibrio cholerae can mount an immunity-independent resistance against type VI-secretion system via envelope stress response modulators – Rcs phosphorelay ( E. coli ) and two-component systems BaeSR ( E. coli ) and WigKR ( V. cholerae ). Authors showed that responses include such phenotypes as up-regulation of osmotic-response genes, increased capsular polysaccharide synthesis, and general cell integrity preservation ( Hersch et al, 2020 ). It is tempting to speculate, that BfmRS system might similarly cause immunity-independent resistance phenotype against CDI as in addition to the role in capsule formation in some A. baumannii strains, it also contributes to resistance to high osmolarity and desiccation ( Farrow et al, 2018 ).…”

Accumulation of dead cells from contact killing facilitates coexistence in bacterial biofilms

“…Such physical protection stands in stark contrast to active, species-dependent defence mechanisms that are controlled genetically [36,38,40,41]. Physical barriers represent an emergent first line of defence that do not require active sensing or control and are species independent.…”