Abstract
Evolutionary arms races are broadly prevalent among organisms including bacteria, which have evolved defensive strategies against various attackers. A common microbial aggression mechanism is the type VI secretion system (T6SS), a contact-dependent bacterial weapon used to deliver toxic effector proteins into adjacent target cells. Sibling cells constitutively express immunity proteins that neutralize effectors. However, less is known about factors that protect non-sibling bacteria from T6SS attacks independently of cognate immunity proteins. In this study, we observe that human Escherichia coli commensal strains sensitive to T6SS attacks from Vibrio cholerae are protected when co-cultured with glucose. We confirm that glucose does not impair V. cholerae T6SS activity. Instead, we find that cells lacking the cAMP receptor protein (CRP), which regulates expression of hundreds of genes in response to glucose, survive significantly better against V. cholerae T6SS attacks even in the absence of glucose. Finally, we show that the glucose-mediated T6SS protection varies with different targets and killers. Our findings highlight the first example of an extracellular small molecule modulating a genetically controlled response for protection against T6SS attacks. This discovery may have major implications for microbial interactions during pathogen-host colonization and survival of bacteria in environmental communities.
Highlights
Evolutionary arms races are broadly prevalent among organisms including bacteria, which have evolved defensive strategies against various attackers
When V. cholerae C6706* and E. coli MG1655 cells are co-cultured on LB medium containing 0.4% glucose (LBG), reflecting physiological levels, the number of recovered E. coli cells is significantly increased (~ 1000-fold) compared to co-cultures on LB with no added glucose (Fig. 1a)[32,33]
In addition to immunity proteins that neutralize effectors, it is becoming more apparent that arms races between T6SS killers and target bacterial cells have led to the emergence of diverse defensive mechanisms we are beginning to identify[17,34,53,54,55]
Summary
Evolutionary arms races are broadly prevalent among organisms including bacteria, which have evolved defensive strategies against various attackers. A common microbial aggression mechanism is the type VI secretion system (T6SS), a contact-dependent bacterial weapon used to deliver toxic effector proteins into adjacent target cells. We observe that human Escherichia coli commensal strains sensitive to T6SS attacks from Vibrio cholerae are protected when co-cultured with glucose. Our findings highlight the first example of an extracellular small molecule modulating a genetically controlled response for protection against T6SS attacks This discovery may have major implications for microbial interactions during pathogen-host colonization and survival of bacteria in environmental communities. Since glucose decreases pathogen colonization of the intestinal tract and alters interactions between V. cholerae and E. coli cells in h osts[25,26], induced protection from T6SS attacks by metabolites may be common in microbial communities of environmental and human health importance
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