The Type VI Secretion System (T6SS) is a common contact-dependent mechanism of bacterial antagonism. Vibrio cholerae and many other Gram-negative pathogens use the T6SS to compete against other cells by delivering toxic effector proteins into neighboring target cells. Mechanisms of protection include cognate immunity protein expression (preventing self and sibling cell intoxication), stress responses, and secreted polysaccharides; Importantly, external environmental factors that mediate defense have not been described.

We find that exogenous glucose can trigger a response in human commensal Escherichia coli that protects against V. cholerae’s T6SS attack. Further, an E. coli strain engineered to lack the cAMP receptor protein (CRP), which regulates expression of hundreds of genes in response to glucose, survives T6SS attacks independently of any environmental signal. We show that this protection varies with T6SS killers encoding different toxic effectors, and with target cells species. These findings suggest an ‘evolutionary arms race’ between T6SS killers and target bacterial cells, with implications for microbial interactions during host colonization by pathogens."