Carlos São-José

Phage Biology Research and Infection Control

The PhaBRIC lab addresses key biologic questions concerning the interaction of phages with their bacterial hosts. As a major research topic, the lab seeks to understand the action of phage proteins that disrupt the bacterial cell envelope, and to explore this knowledge to develop innovative strategies to fight antibiotic-resistant bacteria.

Infection diseases caused by antibiotic-resistant bacteria are widely recognized as a one of the major threats to human health and global economy. High societal impacts are foreseen if alternative antimicrobial agents are not found to compensate the failure of conventional antibiotics. Bacteriophages and their bactericidal functions (re)gained much interest in the last years as promising therapeutic options, with emerging technological approaches building on solid knowledge accumulated after decades of research on these special viruses. The PhaBRIC lab studies molecular details of the phage-host cell interactions taking place during virus entry to bacteria, and then at the end of viral replication when the phage progeny is released to the extracellular space through bacteriolysis. The lab has pioneering work on the proteins and mechanisms that phages use to target and compromise the different layers of the bacterial cell envelope. This fundamental knowledge has been used to devise phage-based agents that specifically target and kill drug-resistant bacterial pathogens, such as Staphylococcus spp., Enterococcus spp. and Mycobacterium tuberculosis, and which minimize resistance development. PhaBRIC collaborates with the biotech company TechnoPhage in the development of antibacterial products of phage origin.

Tan YZ, Zhang L, Rodrigues J, Zheng RB, Giacometti SI, Rosário AL, Kloss B, Dandey VP, Wei H, Brunton R, Raczkowski AM, Athayde D, Catalão MJ, Pimentel M, Clarke OB, Lowary TL, Archer M, Niederweis M, Potter CS, Carragher B, Mancia F. Cryo-EM Structures and regulation of arabinofuranosyltransferase AftD from Mycobacteria. Mol Cell 2020; 78:683-699.e11. DOI: 10.1016/j.molcel.2020.04.014.
Fernandes S, São-José C. Enzymes and mechanisms employed by tailed bacteriophages to breach the bacterial cell barriers. Viruses. 2018; 10:396. DOI: 10.3390/v10080396.
São-José C. Engineering of Phage-Derived Lytic Enzymes: Improving Their Potential as Antimicrobials. Antibiotics (Basel) 2018; 7:29. DOI: 0.3390/antibiotics7020029.
Gigante AM, Hampton CH, Dillard RS, Gil F, Catalão MJ, Moniz-Pereira J, Wright ER, Pimentel M. The Ms6 mycolyl-arabinogalactan esterase LysB is essential for an efficient Mycobacteriophage-induced lysis. Viruses. 2017; 9:343. DOI: 10.3390/v9110343.
Fernandes S, São-José C. More than a hole: the holin lethal function may be required to fully sensitize bacteria to the lytic action of canonical endolysins. Mol Microbiol. 2016; 102:92-106. DOI: 10.1111/mmi.13448.

Carlos São-José

Group Leader

Email: csaojose@ff.ulisboa.pt

Phone: (+351) 217946420 (Ext. 14223)

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Faculdade de Farmácia da Universidade de Lisboa | Av. Professor Gama Pinto
1649-003 Lisboa | Portugal


Phone | +351 217 946 400
Fax | +351 217 946 470
Web | www.imed.ulisboa.pt
Email | imed.ulisboa@ff.ulisboa.pt

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