Sérgio R. Filipe Lab
We study how bacteria synthesize a major component of their cell surface, the peptidoglycan, while simultaneously preventing the infected host from detecting this inflammatory macromolecule that can trigger an innate immune response.
Sérgio R. Filipe
Phone (+351) 214469537
The main interest of the laboratory of Bacterial Cell Surfaces and Pathogenesis is to understand how bacteria synthesize their peptidoglycan, a large macromolecule from their cell wall that surrounds and protects bacteria. The synthesis of peptidoglycan, which is involved in determining the bacterial shape and that serves as an attachment site for extracellular proteins, is the target of different families of antibiotics and it seems to play an important role in detection of bacterial infection by different host immune systems.
In the last few years an increasing number of reports have shown that peptidoglycan (or its small components) is able to induce an inflammatory response in different hosts. In order to understand how the infected host senses this macromolecule, we must learn how bacteria try to disguise it and how this molecule is synthesized, organized, modified and degraded during the regular bacterial cell cycle.
The research program being followed in the laboratory of Bacterial Cell Surfaces and Pathogenesis has the following aims:
- to understand how the different chemical composition and the structure of the PGN found among bacteria determine their recognition by the host.
- to determine whether the regular metabolism of the PGN, that occurs as bacteria divide into two daughter cells, can interfere with the accessibility of the PGN to the host PGN detectors.
- to ask whether PGN is hidden from the infected host by molecules that are found in different bacteria covalently attached to PGN, such as bacterial capsular polysaccharides.
- to identify particular strategies that bacteria may have found to hide or eliminate the synthesis of the inflammatory PGN macromolecule, namely in obligatory intracellular bacterial pathogens such as Chlamydia trachomatis.
We expect that understanding the role of PGN in the trigger of inflammatory processes will allow us to devise strategies to modulate the inflammatory response of a given host during bacterial infection.
- Ana Rita Narciso, PhD student
- Denise Coutinho, PhD student
- Gonçalo Covas, PhD student
- Joana Figueiredo, PhD Student
Covas G, Vaz F, Henriques G, Pinho MG, Filipe SR. 2016. Analysis of Cell Wall Teichoic Acids in Staphylococcus aureus.
Methods Mol Biol. 1440: 201-13. PMID: 27311674. DOI: 10.1007/978-1-4939-3676-2_15
Greene NG, Narciso AR, Filipe SR, Camilli A. 2015. Peptidoglycan Branched Stem Peptides Contribute to Streptococcus pneumoniae Virulence by Inhibiting Pneumolysin Release. PLoS Pathog. 11: e1004996. PMID: 26114646. DOI: 10.1371/journal.ppat.1004996.
Atilano ML, Pereira PM, Vaz F, Catalão MJ, Reed P, Grilo IR, Sobral RG, Ligoxygakis P, Pinho MG, Filipe SR. 2014. Bacterial autolysins trim cell surface peptidoglycan to prevent detection by the Drosophila innate immune system. Elife. 3: e02277. DOI: 10.7554/eLife.02277.
For further information please visit the laboratory's website
Estamos constantemente em contacto com um mundo microscópico que está presente em qualquer ponto do planeta e interage connosco desde o nosso nascimento. As bactérias fazem parte deste mundo e podem ser benéficas ou provocar doença ao hospedeiro infectado.
Estratégias para detectar, e monitorizar, a presença das bactérias invasoras são essenciais a sobrevivência de plantas e animais ao prevenirem as consequências nefastas de um crescimento bacteriano excessivo ou da produção de componentes bacterianos tóxicos.
O nosso grupo estuda como é que a parede celular bacteriana é sintetizada pelas bactérias e é reconhecida pelo hospedeiro. Embora este polímero tenha uma função de blindagem e protecção nas bactérias, está acessível ao reconhecimento pelo sistema imunitário do hospedeiro e é capaz despoletar uma resposta inflamatória. Gostaríamos de conseguir interferir com os mecanismos de camuflagem que as bactérias usam para não serem detectadas pelo nosso sistema imune.