LAUSR

Protein secretion systems are multi-subunit machines located in the cell envelopes of prokaryotes. They provide a fundamental route through which bacteria interact with their surroundings. Outside of the laboratory, bacteria are rarely found in monoculture, usually existing in mixed-species communities. Some of the most complex bacterial communities are found in association with higher eukaryotes; for example the human gastrointestinal tract represents one of the most densely colonised habitats described to date (e.g., [1]). Within such a community, bacteria interact not only with other microorganisms but often also with host components. Many of these interactions are mediated through secreted proteins. Interbacterial competition plays a key role in the dynamics of microbial communities and bacterial colonisation. Toxins targeting a variety of cellular functions are secreted from aggressor cells either via specific secretion machineries or, in the case of colicins and pyocins, through lysis of the producing cell. In both cases, the costs of toxin production and secretion are high, and expression of the requisite genes are tightly regulated [2,3]. In gram-negative bacteria, type V and type VI secretion systems (T5SS and T6SS) mediate interbacterial antagonism via toxin delivery to neighbouring cells. The antibacterial activity of the T6SS promotes colonisation by the producing organism (e.g., [4]). Regulation of the T6SS can be preor posttranslational depending on the system. In Pseudomonas aeruginosa assembly of the T6SS is dynamic and controlled through cycles of threonine phosphorylation mediated via a membrane-bound kinase termed PpkA (reviewed in [5]). The activity of PpkA is modulated by cell envelope damage—specifically, it is activated by incoming T6SS attack from a neighbouring bacterium, thereby promoting T6-dependent counterattack [6]. Membrane damage from an incoming conjugative pilus or polymyxin B can likewise trigger this response [7]. A specific toxin effector from a competitor T6SS has also been shown to activate the T6SS [8] in a manner reminiscent of colicin activation by the SOS response following colicin-mediated DNA damage (Fig 1). Additional signals from quorum sensing and nutrient availability are also integrated into these control mechanisms [9]. Many gram-positive bacteria produce a type VII protein secretion system (T7SS). Studies in mycobacteria have shown that the system plays a critical role in pathogenesis and intracellular trafficking [10]. However, there is a growing appreciation that firmicutes utilise the T7SS primarily for bacterial antagonism. Two T7-dependent antibacterial toxins have been identified and characterised in Staphylococcus aureus and three in Streptococcus intermedius [11–13]. In most firmicutes studied to date, the T7SS appears to be carefully regulated and is poorly active under laboratory conditions [14,15]. For example, the S. aureus T7SS locus is under complex transcriptional control [16] and is up-regulated in response to decreased membrane fluidity [17]. It is also regulated at the posttranslational level as secretion activity is generally very inefficient, but can be stimulated in some strain backgrounds by the presence of hemin [18]. The study by Chaterjee and colleagues has investigated environmental cues that activate the T7SS in the firmicute Enterococcus faecalis [19], a bacterium found in the gut microbiota of PLOS GENETICS