Bacterial danger sensing

Abstract

Here we propose that bacteria detect and respond to threats posed by other bacteria via an innate immune-like process that we term danger sensing. We find support for this contention by reexamining existing literature from the perspective that intermicrobial antagonism, not opportunistic pathogenesis, is the major evolutionary force shaping the defensive behaviors of most bacteria. We conclude that many bacteria possess danger sensing pathways composed of a danger signal receptor and corresponding signal transduction mechanism that regulate pathways important for survival in the presence of the perceived competitor.

Keywords: Gac/Rsm; competence; interbacterial; subinhibitory antibiotics; type VI secretion.

Figure 1. Examples of danger sensing pathways

Danger sensing can be broken into three components: (1) one or more danger cues; (2) a danger sensing signal transduction mechanism; and (3) a danger response regulon. (a) Gac/Rsm-mediated response to cell lysis. (1) A competitor (blue) lyses a subset of P. aeruginosa cells (green), e.g. through production of a toxin (red circle). (2) Left: The Gac/Rsm danger sensing signal transduction pathway in the inactive state. Right: A mislocalized self-derived molecule from lysed P. aeruginosa (green circles) stimulates this pathway to relieve negative regulation of danger response factors. (3) The outcome of danger sensing is the increased production of factors (brown circles) that target competitor cells and defend against antagonism. (b) PhoPQ-mediated response to DNA and AMPs. (1) Competitor cells (blue) produce AMPs that damage cell membranes of target cells (green), which may lead to cell lysis and DNA release. (2) Left panel: eDNA from lysed cells chelates cations, reducing the local Mg²⁺ (black circles) concentration; additionally AMPs themselves can be sensed. Middle: Low Mg²⁺ concentrations and/or AMPs stimulate PhoPQ. Right panel: The PhoPQ regulon mediates outer membrane modifications that reduce its negative charge. (3) Resulting membrane alterations protect cells from assault by AMPs. (c) Diffusible signal factor (DSF) “eavesdropping”. (1) The quorum sensing signal, DSF, is produced by S. maltophilia (blue) and sensed by P. aeruginosa (green). (2) Left: A putative sensor kinase (PA1396) in its inactive state. Middle: PA1396 detects DSF and stimulates its regulon. Right: Gene expression leads to outer membrane modifications and increased production of exopolysaccharides. (3) This cellular program may promote survival of P. aeruginosa in the presence of S. maltophilia.