Bacterial secretion machinery (Dr. Regaiolo)

Type VI secretion systems in Photorhabdus luminescens

Bacteria live in complexes environmental niches which force them to interact with different microorganism, thus developing different interaction mechanisms to improve their fitness. Secretion systems are essential for bacteria to produce: i) surface structures for adhesion, ii) promote aggregation and bacterial motility, iii) to secrete cell effectors which defeat and reprogram host cells. The huge array of bacterial secretion system functions as attacking machinery towards host cells. Secretion systems arm bacteria to compete against other microbes or to share nucleic acids, influencing virulence evolution. Among them, the T6SS is a cell envelope-spanning machine that translocates toxic effector proteins into eukaryotic and prokaryotic cells and has a pivotal role in pathogenesis and bacterial competition. The T6SS was functionally defined in 2006and is broadly distributed among Proteobacteria. The T6SS is composed of 13 conserved, essential core components and several accessory components. The exact role of the T6SS is not clear yet. Investigations of T6SS in different pathogens have yielded bewildering results that range from necessary to not necessary to inhibitory for virulence. Moreover, the T6SS is used to influence the social dynamics of the microbial community. T6SS effectors can be translocated into the periplasmic space of co-inhabiting bacteria to compromise their fitness. These effectors are required for contact-dependent growth inhibition and have cognate inhibitor proteins (immunity protein) that protect the hunter microorganisms from self intoxication. Photorhabdus luminescens is a Gram-negative entomopathogenic bacteria which live in symbiosis with nematodes. Its ability to interact with different organism (plant, nematodes and larvae) and live in different environments (i.e., larvae haemocoel, nematodes gut and rhizosphere) makes this microorganism a good candidate to investigate it T6SS weaponry machine and the T6SS-associated effectors.

This project is investigating the T6SS secretion system(s) in P. luminescens using multidisciplinary approaches. Bioinformatics analysis pointed out four different T6SS which present diverse gene organization, and a pool of T6SS related effectors. The characterization of these effectors, their mode of action and delivery (using molecular biology techniques, microscopy and protein prediction tools) into host cells and their influence on the Photorhabdus fitness will unravel new therapeutic solution to fight pathogens.

Pisarz, F.; Glatter, T.; Süss, D-T. M.; Heermann, R.; Regaiolo, A. (2024). The Type VI secretion systems of the insect pathogen Photorhabdus luminescens are involved in interbacterial competition, motility and secondary metabolism. The Microbe. doi: org/10.1016/j.microb.2024.100067

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Dr. Alice Regaiolo
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