The infection biology laboratory aims to understand the mechanisms by which bacterial pathogens manipulate animal host cells. This basic knowledge might help to develop strategies to combat infectious diseases.
Luís Jaime Mota
Phone +351 21 1157784
We are interested in molecular and cellular mechanisms underlying bacterial virulence. We focus on intracellular bacterial pathogens that multiply within host cells in unique membrane-bound organelles (pathogen-containing vacuoles), using Chlamydia trachomatis and Salmonella enterica as experimental models.
C. trachomatis serovars are human pathogens causing ocular and genital infections. About 80 million people are affected by C. trachomatis ocular infections and > 90 million new C. trachomatis genital infections occur each year. Chlamydial infections can lead to chronic conditions such as blindness or infertility. C. trachomatis are obligate intracellular bacteria and breakthroughs on how to genetically manipulate them have only recently been published.
S. enterica serovars infect a wide range of animals and cause gastrointestinal and systemic diseases in humans. Worldwide, it is estimated that over half a million deaths occur each year due to typhoid fever (caused mainly by serovar Typhi), and over 3 million deaths due to non-typhoidal Salmonella infections. S. enterica are facultative intracellular bacteria, and serovar Typhimurium is an excellent model to study host-pathogen interactions. This is due to the availability of sophisticated genetic tools, and of established tissue culture and animal models of infection.
Like several other Gram-negative pathogenic bacteria, Chlamydia and Salmonella employ a type III secretion system to inject effector proteins into their eukaryotic host cells. The effector proteins modulate several host cell functions to benefit the bacteria. Both Chlamydia and Salmonella use type III effector proteins to invade non-phagocytic cells, to replicate intracellularly within their vacuoles, and to modulate host immune responses.
Generally, we study the function of type III secretion effectors of Chlamydia and Salmonella. Although many Salmonella effectors are well studied several other remain largely uncharacterised. Our studies are focused in poorly characterised Salmonella effectors. Much less is known about the function of chlamydial effectors. To study these proteins, we are using Yersinia enterocolitica as heterologous host to screen for type III secretion signals within hypothetical proteins of C. trachomatis that we selected from bioinformatics analyses. We are in the process of generating antibodies against the candidates found, to then test by immunofluorescence microscopy if they are secreted in infected cells. We will then choose proteins for further analyses of their molecular functions. For example, to find host cell target by performing unbiased protein-protein interaction screens. In addition, we aim to understand the function of a specific subset of known C. trachomatis type III secretion substrates (the Inc proteins) and we have been screening for type III secretion chaperones of C. trachomatis.
- Irina Franco, Post-Doc
- Lia Domingues, PhD student
- Maria da Cunha, PhD student
- Filipe Almeida, PhD student
- Sara Pais, Research student (BI)
- Catarina Milho, Research student (BI)
- Almeida, F., Borges, V, Ferreira, R., Borrego, M. J., Gomes, J. P, and Mota, L. J. (2012). Polymorphisms in Inc proteins and differential expression of _inc_ genes among _Chlamydia trachomatis_ strains correlate with invasiveness and tropism of lymphogranuloma venereum isolates. J Bacteriol. 194:6574-85. (doi: 10.1128/JB.01428-12)
- McGourty, K. Thurston, T. L., Matthews, S.A., Pinaud, L., Mota, L.
J., and Holden, D.W. (2012). _Salmonella_ inhibits retrograde trafficking of mannose-6-phosphate receptors and lysosome function.
Science. 338:963-7 (doi: 10.1126/science.1227037)
- Schroeder, N, Mota, L. J., and Méresse, S. (2011).
Salmonella-induced tubular networks. Trends Microbiol. 19: 268-77.
For further information please visit the laboratory's website
Biologia da Infecção (PT)
As infecções microbianas são uma das maiores causas de doença e morte em todo o mundo. Uma das estratégias fundamentais para as combater é estudar os mecanismos através dos quais os micróbios são capazes de alterar o funcionamento das células humanas. Este conhecimento básico poderá depois ser transplantado no desenvolvimento de vacinas ou terapias específicas.
Nós estudamos Chlamydia trachomatis (que causa infecções oculares e infecções sexualmente transmissíveis) e Salmonella enterica (que causa gastroenterite e febre tifóide). Salmonella é também um excelente modelo para estudar aspectos fundamentais da interacção hospedeiro-bactéria patogénica. Ambas as bactérias possuem um sistema de secreção consistindo numa espécie de seringa, que serve para injectar um “cocktail” de proteínas (efectores) nas células do hospedeiro. Os efectores manipulam as células do hospedeiro em benefício da bactéria. No nosso laboratório estudamos a função de efectores de Chlamydia e de Salmonella.