Our main interest is to understand molecular and cellular mechanisms underlying bacterial virulence. In particular, we study processes by which intracellular bacterial pathogens alter the normal functioning of eukaryotic host cells. We focus in a virulence mechanism consisting in the one-step injection of bacterial effector proteins into host cells through specialized secretion systems. Bacterial effector proteins have been shown to act on a vast array of eukaryotic cell functions, such as cytoskeleton dynamics, cell signalling or vesicular transport. Our main research focus has been to study the function of effector proteins from bacterial pathogens that cause relevant infections in humans (Chlamydia, Legionella, and Salmonella) and which possess type III or type IV secretion systems that are essential for their virulence.
Chlamydia trachomatis is an obligate intracellular bacterium which is an important human pathogen that delivers several type III secretion effectors proteins into host cells. For a long time, studies of C. trachomatis molecular pathogenesis have been hindered by lack of genetic tools for its manipulation. However, these tools have recently been developed and we are using them in our ongoing studies to identify and characterize C. trachomatis type III secretion effectors:
Some of the C. trachomatis type III secretion substrates are secreted into the lumen of the inclusion during infection
We previously identified candidate type III secretion substrates of C. trachomatis (da Cunha et al, BMC Microbiology, 2014). Among these, we showed that CT142, CT143, and CT144 are delivered into the lumen of the vacuole (known as inclusion) where Chlamydia resides intracellularly. This supported that type III secretion substrates are not necessarily delivered into the cytoplasm of host cell.
C. trachomatis (labelled with Hsp60) producing and secreting eiptope-tagged CT143 into the lumen of the vacuole.
A C. trachomatis Inc protein binds a centrosomal protein, which is recruited to the vacuolar membrane
Chlamydia uses its type III secretion system to transport about 50 proteins, known as Incs, into the membrane of the inclusion. We found that CT288 binds and likely controls the function of a human centrosomal protein (CCDC146) that we have shown to surround the inclusion membrane during infection.
Co-localization of CT288 and CCDC146 at the inclusion membrane
- “Identification and characterization of Chlamydia trachomatis virulence proteins”, FCT-MCTES, Total and Unit funding: €239,075, Jaime Mota (PI)
- “A multidisciplinary approach to study Chlamydia trachomatis inclusion membrane (Inc) proteins”, FCT-MCTES, Total and Unit funding: €199,236, Jaime Mota (PI)
- “Identification of new virulence mechanisms of a Legionella pneumophila strain recently isolated from a major outbreak in Portugal”, ESCMID, Total and Unit funding: €20,000, Irina Franco (PI)
da Cunha, M; Pais, SV; Bugalhao, JN; Mota, LJ. 2017. The Chlamydia trachomatis type III secretion substrates CT142, CT143, and CT144 are secreted into the lumen of the inclusion. PLoS One, 12, DOI: 10.1371/journal.pone.0178856
Inacio, AS; Nunes, A; Milho, C; Mota, LJ; Borrego, MJ; Gomes, JP; Vaz, WLC; Vieira, OV. 2016. In Vitro Activity of Quaternary Ammonium Surfactants against Streptococcal, Chlamydial, and Gonococcal Infective Agents. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 60, DOI: 10.1128/AAC.00166-16
Domingues, L; Ismail, A; Charro, N; Rodriguez-Escudero, I; Holden, DW; Molina, M; Cid, VJ; Mota, LJ. 2016. The Salmonella effector SteA binds phosphatidylinositol 4-phosphate for subcellular targeting within host cells. CELLULAR MICROBIOLOGY, 18, DOI: 10.1111/cmi.12558
Bugalhao, JN; Mota, LJ; Franco, IS. 2016. Identification of regions within the Legionella pneumophila VipA effector protein involved in actin binding and polymerization and in interference with eukaryotic organelle trafficking. MicrobiologyOpen, 5, DOI: 10.1002/mbo3.316
Borges, V; Pinheiro, M; Antelo, M; Sampaio, DA; Vieira, L; Ferreira, R; Nunes, A; Almeida, F; Mota, LJ; Borrego, MJ; Gomes, JP. 2015. Chlamydia trachomatis In Vivo to In Vitro Transition Reveals Mechanisms of Phase Variation and Down-Regulation of Virulence Factors. PLoS One, 10, DOI: 10.1371/journal.pone.0133420