A Transcriptional Regulatory Mechanism Finely Tunes the Firing of Type VI Secretion System in Response to Bacterial Enemies

Abstract

The ability to detect and measure danger from an environmental signal is paramount for bacteria to respond accordingly, deploying strategies that halt or counteract potential cellular injury and maximize survival chances. Type VI secretion systems (T6SSs) are complex bacterial contractile nanomachines able to target toxic effectors into neighboring bacteria competing for the same colonization niche. Previous studies support the concept that either T6SSs are constitutively active or they fire effectors in response to various stimuli, such as high bacterial density, cell-cell contact, nutrient depletion, or components from dead sibling cells. For Serratia marcescens, it has been proposed that its T6SS is stochastically expressed, with no distinction between harmless or aggressive competitors. In contrast, we demonstrate that the Rcs regulatory system is responsible for finely tuning Serratia T6SS expression levels, behaving as a transcriptional rheostat. When confronted with harmless bacteria, basal T6SS expression levels suffice for Serratia to eliminate the competitor. A moderate T6SS upregulation is triggered when, according to the aggressor-prey ratio, an unbalanced interplay between homologous and heterologous effectors and immunity proteins takes place. Higher T6SS expression levels are achieved when Serratia is challenged by a contender like Acinetobacter, which indiscriminately fires heterologous effectors able to exert lethal cellular harm, threatening the survival of the Serratia population. We also demonstrate that Serratia’s RcsB-dependent T6SS regulatory mechanism responds not to general stress signals but to the action of specific effectors from competitors, displaying an exquisite strategy to weigh risks and keep the balance between energy expenditure and fitness costs.

Killing with proficiency: Integrated post-translational regulation of an offensive Type VI secretion system

“…It has been reported that the RcsAB two-component system regulates expression of the S . marcescens RM66262 T6SS at a transcriptional level, and may upregulate the expression of the T6SS in response to effectors delivered by competitor cells [ 36 ]. This system may offer some parallels with the ‘PARA’ response in P .…”

“…coli , but cannot intoxicate T6SS-inactive mutants of S . marcescens [ 36 ]. However, we do not believe that this conclusion can be generally applied to all S .…”

Bacterial antagonism in host-associated microbial communities

“…Many colicins are part of the LexA regulon (LexA is the master regulator of the SOS response to DNA damage). Pseudomonas aeruginosa and Serratia marcescens fire their T6SS in response to attack by a T6SS-mediated attack from other species (77,84,85). Some antimicrobial systems are regulated by specific signals, such as the absence of a nutrient, and others use a Trojan horse strategy (by modifying the toxin to look like a nutrient) to target competitors that consume a specific resource.…”

Expanding the molecular weaponry of bacterial species

“…The finding of T6SS effectors with no observable antibacterial activity has also been documented for Acinetobacter baumannii (9,10). It is possible that the role of these effectors is dependent on environmental conditions, as was determined for Tge2 (8), or that they have eukaryotic targets.…”