Abstract
SummaryContact‐dependent growth inhibition (CDI) allows bacteria to recognize kin cells in mixed bacterial populations. In Escherichia coli, CDI mediated effector delivery has been shown to be species‐specific, with a preference for the own strain over others. This specificity is achieved through an interaction between a receptor‐binding domain in the CdiA protein and its cognate receptor protein on the target cell. But how conserved this specificity is has not previously been investigated in detail. Here, we show that class II CdiA receptor‐binding domains and their Enterobacter cloacae analog are highly promiscuous, and can allow for efficient effector delivery into several different Enterobacteriaceae species, including Escherichia, Enterobacter, Klebsiella and Salmonella spp. In addition, although we observe a preference for the own receptors over others for two of the receptor‐binding domains, this did not limit cross‐species effector delivery in all experimental conditions. These results suggest that class II CdiA proteins could allow for broad‐range and cross‐species growth inhibition in mixed bacterial populations.
Highlights
Bacteria live in complex microbial communities where they interact and compete with other microbes for resources
Closely homologous binding domains to the CdiA protein of E. coli UPEC F11 (CdiAF11) were identified in Salmonella typhi, E. coli CFT073/E. coli Nissle 1917 (Fig. S1), which have significantly different Outer Membrane Protein C (OmpC) extracellular loops from UPEC 536, UPEC F11 and each other (Fig. S2). These findings suggest that species-specificity could be achieved by very small amino acid differences in the receptor and/or receptor-binding domain. 126 Class II CdiA-OmpC dependent effector delivery is promiscuous
To test how the differences between OmpC proteins affected class II mediated toxin delivery, we replaced the chromosomal ompC ORF of E. coli MG1655 with the ompC from E. coli strains UPEC F11 or Nissle 1917/CFT073, as well as the ompC from Enterobacter cloacae and Salmonella typhimurium/typhi (OmpC's from S. typhimurium and typhi are identical)
Summary
Bacteria live in complex microbial communities where they interact and compete with other microbes for resources. Delivery of anti-bacterial toxins to neighboring cells can occur through different mechanisms including cell-cell contact mediated effector delivery by type IV (Souza et al, 2015), V (Aoki et al, 2005), VI (Hood et al, 2010), and VII Casabona, Kneuper, Chalmers, & Palmer, 2016) secretion systems Common for all these toxin delivery systems is that kin-cells express an immunity or anti-toxin protein that protects against the toxic activity of its cognate effector, allowing kin cells to survive effector delivery when non-kin cells are killed or growth inhibited Upon interaction with a receptor on the cell surface of a neighboring cell, the C-terminal domain is cleaved off and delivered into the recipient cell (Aoki et al, 2010; Ruhe et al, 2018; Webb et al, 2013). The toxic activities of the C-terminal encoded toxic effectors range from nucleases that degrade tRNA, rRNA and DNA to ionophore toxins that dissipate the proton motive force of the bacterial cell
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