PUBLICATIONS

T6SS ARMOR

*Toska J, *Ho BT, Mekalanos JJ. Exopolysaccharide protects Vibrio cholerae from exogenous attacks by the type 6 secretion system. Proc Natl Acad Sci U S A. 2018 Jul 31;115(31):7997-8002. doi: 10.1073/pnas.1808469115.

In this work we found that exopolysaccharide (EPS) produced by V. cholerae can protect against exogenous type 6 secretion system (T6SS) attacks from different bacterial species. This protection does not affect the ability of the EPS-producing cell to use their own T6SS to attack other bacteria, indicating that EPS does not simply increase the physical distance between cells to afford protection.

TRACKING IN VIVO BACTERIAL CELL-CELL CONTACTS

*Fu Y, *Ho BT, Mekalanos JJ. Tracking Vibrio cholerae cell-cell interactions during infection reveals bacterial population dynamics within intestinal microenvironments. Cell Host Microbe. 2018 Feb 14;23(2):274-281.e2. doi: 10.1016/j.chom.2017.12.006.

We examined V. cholerae bacterial population structure within the host intestine, using DNA conjugation as a genetic reporter for bacterial cell-cell contacts along with measurements of antagonistic T6SS-mediated interactions. These observations revealed that contact-dependent cell-cell interactions and the T6SS play specific roles in distinct intestinal microenvironments.

ENGINEERING T6SS EFFECTORS

*Ho BT, *Fu Y, Dong TG, Mekalanos JJ. Vibrio cholerae type 6 secretion system effector trafficking in target bacterial cells. Proc Natl Acad Sci U S A. 2017 Aug 29;114(35):9427-9432. doi: 10.1073/pnas.1711219114.

We were able to alter the prey target range of the antibacterial activity of the T6SS. We also uncovered a cryptic secretion mechanism(s) for delivering protein substrates from the bacterial cytosol to the periplasm. T6SS effectors exploit this mechanism to circumvent misdelivery into incorrect subcellular compartments of target bacteria.

T6SS ATTACKS AGAINST TARGETING DNA CONJUGATION DONORS

Ho BT, Basler M, Mekalanos JJ. Type 6 secretion system-mediated immunity to type 4 secretion system-mediated gene transfer. Science. 2013 Oct 11;342(6155):250-3. doi: 10.1126/science.1243745.

We found that P. aeruginosa uses its T6SS to counterattack against conjugative donor bacteria that engage in mating pair formation. This T6SS response represents a tool used by P. aeruginosa to potentially block the acquisition parasitic foreign DNA.

PAAR DOMAIN-CONTAINING PROTEINS ARE T6SS SECRETION SUBSTRATES

*Shneider MM, *Buth SA, Ho BT, Basler M, Mekalanos JJ, Leiman PG. PAAR-repeat proteins sharpen and diversify the type VI secretion system spike. Nature. 2013 Aug 15;500(7462):350-353. doi: 10.1038/nature12453.

We identified a novel class of T6SS effectors, determined their crystal structure and characterized their role in secretion in several different bacterial species.

T6SS CAN RETALIATE AGAINST EXOGENOUS T6SS ATTACKERS

Basler M, Ho BT, Mekalanos JJ. Tit-for-tat: type VI secretion system counterattack during bacterial cell-cell interactions. Cell. 2013 Feb 14;152(4):884-94. doi: 10.1016/j.cell.2013.01.042.

We observed that the T6SS of P. aeruginosa assembles and delivers its toxic payload in an aimed response to retaliate against exogenous attacks by the T6SS of adjacent bacteria cells. This work provided evidence for a bacterial “tit-for-tat” evolutionary strategy that controls the social interaction among different bacterial species.

IDENTIFICATION OF NOVEL T6SS EFFECTOR/IMMUNITY PROTEIN PAIRS USING TN-SEQ

Dong TG, Ho BT, Yoder-Himes DR, Mekalanos JJ. Identification of T6SS-dependent effector and immunity proteins by Tn-seq in Vibrio cholerae. Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2623-8. doi: 10.1073/pnas.1222783110.

We developed a new approach for identifying T6SS effectors in a given bacterial strain by screening for the essentiality of cognate immunity proteins while grown on an agar surface. We applied this approach to identify the major T6SS effectors and their cognate immunity proteins in V. cholerae.

GENETIC DEFINITION OF THE VIBRIO CHOLERAE T6SS

Zheng J, Ho B, Mekalanos JJ. Genetic analysis of anti-amoebae and anti-bacterial activities of the type VI secretion system in Vibrio cholerae. PLoS One. 2011;6(8):e23876. doi: 10.1371/journal.pone.0023876.

We genetically defined the genes essential to different aspects of T6SS function in V. cholerae, including substrate secretion and toxicity toward eukaryotic cells and other bacteria.

CHROMOSOME DYNAMICS DURING SISTER SEPARATION

Joshi MC, Bourniquel A, Fisher J, Ho BT, Magnan D, Kleckner N, Bates D. Escherichia coli sister chromosome separation includes an abrupt global transition with concomitant release of late-splitting intersister snaps. Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2765-70. doi: 10.1073/pnas.1019593108.

We explored the basis for segregation of sister chromosomes in bacteria by analyzing DNA replication, chromosome segregation, and global nucleoid dynamics in E. coli over time in the cell cycle.