Cell-to-cell signalling during pathogenesis

Abstract

Pathogenic bacteria produce virulence factors only when they sense they are in a location in which the energy required for pathogenesis is warranted. One environmental factor monitored by pathogens is population density, either of its own population or of the population of a host's endogenous flora. To date, four systems have been described which allow pathogens to regulate virulence genes in a population-dependent manner. These systems are found in both Gram-positive and Gram-negative cells and utilize various mechanisms to control gene regulation at a transcriptional level, but they all have one feature in common: they detect autoinducers released by cells belonging to either the pathogen's population or that of the host's flora. This article explores the role of these four signalling systems in bacterial communities and how pathogens use these systems to control genes required during host invasion and infection.

Fig. 1

Three autoinducing strategies in Gram-negative cells. A. AI-1-based strategy using acylated homoserine lactones (red diamonds). AI-1 is synthesized by LuxI and released into the environment. As AI-1 diffuses back into the cell, it interacts with LuxR and results in a cellular response. B. AI-2-based strategy using either R-THMF (green pentagons) or furanosyl borate diester (blue pentagons), both created from LuxS-derived DPD. In Vibrio spp., furanosyl borate diesters interact with LuxP in the periplasm and initiates the LuxQ/LuxO phoshporyl cascade, but in other organisms R-THMF is imported into the cell and phosphorylated by the Lsr system. C. AI-3-based strategy using an autoinducer of unknown structure (yellow hexagons). Autoinducer is released into the environment and sensed by QseC as it diffuses back into the periplasm. QseC then phosphorylates the response regulator QseB. IM, inner membrane; OM, outer membrane.

Fig. 2

AIP-based autoinduction and inhibition in Gram-positive cells using polypeptides (green hexagons). Propeptide, encoded by AgrD, is processed by AgrB and released into the environment where it can either activate the AgrA/AgrC cascade or inhibit the same cascade of a different species. M, membrane; P, peptidoglycan.