Theme Leader: Jorge Humberto Gomes Leitão

The knowledge at the molecular level of mechanisms involved in bacterial regulation of virulence-related gene expression is of critical importance for the rational design of novel strategies and/or molecules to fight bacterial pathogens. A particular focus has been dedicated by our research group to regulatory the RNA chaperone Hfq protein and associated non coding regulatory RNAs that together act as regulators of mRNAs stability to tight regulate bacterial gene expression at the post-transcriptional level. Burkholderia cepacia complex as been the bacterial model system to unveil sRNAs and their cellular functions using molecular multidisciplinary approaches. These bacteria harbor two distinct Hfq-like proteins, whose roles in bacterial physiology remain to be fully elucidate. The exploitation of bacterial proteins as host immune system response modulators, and the development of novel molecules with antimicrobial activity, are also among our research interests.

Our current projects within this subject include

  • Identification and functional analyses of cepacia complex sRNAs playing a role in bacterial pathogenesis
  • Unveil of the specific cellular functions regulated by each of the two RNA chaperones in bacteria of the cepacia complex.
  • Studies on immunogenic proteins and their potential use as protective vaccines
  • Development of novel molecules with antimicrobial activity

Publications

Martina P, Leguizamon M, Prieto CI, Sousa SA, Montanaro P Draghi WO, Stämmler M, Bettiol M, de Carvalho CCCR, Palau J, Figoli C, Alvarez F, Benetti S, Lejona S, Vescina C, Ferreras J, Lasch P, Lagares A, Zorreguietta A, Leitão JH, Yantorno OM, Bosch A. International Journal of Systematic and Evolutionary Microbiology 68:14-18, 2018.

Sousa SA, Feliciano JR, Pita T, Guerreiro SI, Leitão JH. Burkholderia cepacia complex regulation of virulence gene expression: a review. Genes 8 (1), 43, 2017

Sousa SA, Morad M, Feliciano JR, Pita T, Nady S, El-Hennamy RE, Abdel-Rahman M, Cavaco J, Pereira L, Barreto C, Leitão JH. The Burkholderia cenocepacia OmpA-like protein BCAL2958: identification, characterization, and detection of anti-BCAL2958 antibodies in serum from B. cepacia complex-infected Cystic Fibrosis patients. AMB Express 6(1):41., 2017

Alves LG, Pinheiro PF, Feliciano JR, Dâmaso DP, Leitão JH, Martins AM. Synthesis, antimicrobial activity and toxicity to nematodes of cyclam derivatives. International Journal of Antimicrobial Agents 49 (5), 646-649. 2017

Cardoso JMS, Guerreiro SI, Lourenço A, Alves MM, Montemor MF, Mira NP, Leitão JH, Carvalho MFNN. Ag(I) camphorimine complexes with antimicrobial activity towards clinically important bacteria and species of the Candida genus. PLoSOne 9;12(5):e01773552017 2017

Feliciano JR, Grilo AM, Guerreiro SI, Sousa SA, Leitão JH. Hfq: a multifaceted RNA chaperone involved in virulence. FutureMicrobiology 11 (1), 137-151. 2016

Projects

CNCVir – The coding and noncoding virulome of Burkholderia cenocepacia. Project PTDC/BIA-MIC/1615/2014. Funded by FCT, May 2016-April 2019.

RNomics-Bcc: RNomics studies to identify small non-coding RNAs of Burkholderia cepacia complex involved in host-pathogen interactions. Project PTDC/BIA-MIC/119091/2010. Funded by FCT. January 2012 – June 2016.

Development and validation in C. elegans model, of lipid nanoparticles to carry and delivery antimicrobials targeting difficult-to-eradicate bacterial pathogens. Funded by UID/BIO/04565/2013. July 2016 – December 2017.