Bacterial Cell Surfaces and Pathogenesis
We are focused on understanding how bacteria assemble their cell wall as it ensures bacterial resistance to intense osmotic pressures and the concealment of the peptidoglycan (PGN) molecule. PGN is a major component of any bacterial cell surface and a telltale molecule that flags bacteria to the host innate immune system.
Our current research will answer how Streptococcus pneumoniae, a clinically relevant bacterial pathogen, express its resistance to beta-lactam antibiotics; how its surface is decorated with capsular polysaccharides, a major pneumococcal virulence factor, and how this and other Gram-positive bacteria conceal and degrade their surface PGN.
Identification of strategies used by bacteria to build a robust and disguised cell surface
Bacteria are surrounded by an envelope that includes different glycopolymers such as peptidoglycan and capsular polysaccharides. The clarification of how bacteria tune synthesis of these macromolecules, which act as defensive layers, ensuring efficient enclosing of bacteria and their protection from the host, will permit a better understanding of how bacteria propagate during an infection and the design of anti-infective strategies.
We have determined how the Streptococcus pneumoniae ligase that attaches capsule to the bacterial cell wall is directed to the division septum, to ensure full encapsulation of bacteria and their protection from external peptidoglycan binding receptors.
- “Role of the peptidoglycan hydrolases in the interaction of Streptococcus pneumoniae with an infected host”, FCT-MCTES, Total funding: €239,792, Unit funding: €232,292, Sérgio R. Filipe (PI).
- “Clinical significance of Mycobacterium tuberculosis cell wall structural diversity: contribution to novel mechanisms of antibiotic resistance and relevance towards tuberculosis progression and treatment”, FCTMCTES, Total funding: €238,647, Unit funding: €11,250, Sérgio R. Filipe (Collaborator).
- “Molecular and cell biology of imipenem resistance in the human enteric pathogen Clostridium difficile”, FCTMCTES, Total funding: €239,862, Unit funding: €9,375, Sérgio R. Filipe (Collaborator).
Queda, F; Covas, G; Filipe, SR; Marques, MMB. 2020. Assembly of Peptidoglycan Fragments-A Synthetic Challenge. PHARMACEUTICALS, 13, DOI: 10.3390/ph13110392
Queda, F; Covas, G; Silva, T; Santos, CA; Bronze, MR; Canada, FJ; Corvo, MC; Filipe, SR; Marques, MMB. 2019. A top-down chemo-enzymatic approach towards N-acetylglucosamine-N-acetylmuramic oligosaccharides: Chitosan as a reliable template. CARBOHYDRATE POLYMERS, 224, DOI: 10.1016/j.carbpol.2019.115133
Szymczak, P; Rau, MH; Monteiro, JM; Pinho, MG; Filipe, SR; Vogensen, FK; Zeidan, AA; Janzen, T. 2019. A comparative genomics approach for identifying host-range determinants in Streptococcus thermophilus bacteriophages. Scientific Reports, 9, DOI: 10.1038/s41598-019-44481-z
Vaz, F; Kounatidis, I; Covas, G; Parton, RM; Harkiolaki, M; Davis, I; Filipe, SR; Ligoxygakis, P. 2019. Accessibility to Peptidoglycan Is Important for the Recognition of Gram-Positive Bacteria in Drosophila. Cell Reports, 27, DOI: 10.1016/j.celrep.2019.04.103
Monteiro, JM; Covas, G; Rausch, D; Filipe, SR; Schneider, T; Sahl, HG; Pinho, MG. 2019. The pentaglycine bridges of Staphylococcus aureus peptidoglycan are essential for cell integrity. Scientific Reports, 9, DOI: 10.1038/s41598-019-41461-1