Orth Lab


Type VI Secretion System (T6SS)

Bacteria are found in close proximity to other bacteria in various environments, and therefore must compete over resources. To gain advantage over competing bacteria, many Gram negative bacteria utilize a recently-discovered protein secretion machinery called the Type VI Secretion System (T6SS). The T6SS can deliver toxins, called effectors, into neighboring bacterial cells or eukaryotic host cells to mediate interbacterial competition or virulence, respectively.

Vibrio parahaemolyticus encodes two T6SSs. T6SS1 is predominantly found in clinical isolates, whereas T6SS2 is found in all isolates tested to date. We have identified the environmental conditions that induce the secretion from both T6SSs and showed that they are differentially regulated by temperature, salt, quorum sensing, and surface sensing (Salomon et al., PLoS One, 2013). Searching for transcriptional regulators that regulate the expression and activity of T6SS1, we identified H-NS, a bacterial Histone-like nucleoid structuring protein which mediates transcription silencing of horizontally acquired genes, as a repressor of T6SS1 (Salomon et al., Microbiology, 2014).

Monitoring secretion of Hcp, a hallmark secreted protein of T6SSs, shows that activation of surface sensing by addition of the phenamil, an inhibitor of the polar flagellar motor, induces T6SS1 but represses T6SS2 (Salomon et al., PLoS One, 2013).

We found that T6SS1 mediates bacterial killing under warm marine-like conditions (Salomon et al., PLoS One, 2013). Characterizing this T6SS1-mediated killing, we identified three secreted effectors with antibacterial activities. Two of these newly identified effectors shared a common N-terminal motif (called MIX) which we used as a marker to reveal hundreds of previously unindentified T6SS effectors with diverse activities in various bacteria (Salomon et al., PNAS USA, 2014).

MIX-containing effectors group into 5 clans (MIX I-V), and MIX genome neighborhoods link to T6SS components (Salomon et al., PNAS USA, 2014).













Publications on T6SS