Theme Leader: Leonilde M Moreira

Burkholderia cepacia complex (Bcc) is a group of bacteria which often cause chronic respiratory infections in cystic fibrosis patients leading to increased morbidity and mortality. Infections can be transient, but once established, bacteria remain persistently associated with the host for decades, being extremely difficult to eradicate. Our aim is to elucidate the transition undertaken by Bcc bacteria to form chronic infections in the CF lung and to characterize virulence factors. This might lead to the identification of novel therapeutic targets for antimicrobials development.

In opposition to the previous pathogenic interaction, Sinorhizobium meliloti interacts with legume roots inducing the formation of nodules, within which this bacterium fixes nitrogen to ammonia that becomes available to the plant. In preparation for plant colonization bacteria undergo several membrane and cell wall modifications, namely in permeability, transport, and signaling, being this early step the main focus of our research.

Our current projects within this subject include

  • Within-host evolution by combining genome sequencing technologies and phenotypic profiling of Burkholderia multivorans using sequential isolates sampled from chronic lung infections of CF patients [1].
  • Identification of genes/pathways involved in planktonic cellular aggregates formation in B. multivorans and B. cenocepacia.
  • Role of signal transduction pathways in the expression of the mucoid morphotype due to exopolysaccharide biosynthesis in B. multivorans [4,5].
  • Role of tyrosine phosphorylation involving the BceF tyrosine kinase and BceD tyrosine phosphatase of Burkholderia contaminans in host-pathogen interaction [2].
  • Functional analysis of the two-component regulatory system CpxA/CpxR and the EmrR regulator and their relevance in the initial steps of meliloti– plant root interaction [3].

Publications

[1] Silva IN, Santos PM, Santos MR, Zlosnik JEA, Speert DP, Buskirk SW, Bruger EL, Waters CM, Cooper VS, and Moreira LM. (2016). Long-term evolution of Burkholderia multivorans during a chronic cystic fibrosis infection reveals shifting forces of selection. mSystems 1(3):e00029-16. doi:10.1128/mSystems.00029-16.

[2] Ferreira AS, Silva IN, Fernandes F, Pilkington R, Callaghan M, McClean S, and Moreira LM. (2015). The tyrosine kinase BceF and the phosphotyrosine phosphatase BceD of Burkholderia contaminans are required for efficient invasion and epithelial disruption of a cystic fibrosis lung epithelial cell line. Infection and Immunity 83:812-821. doi:10.1128/IAI.02713-14.

[3] Santos MR, Tomás AT, Becker JD, and Moreira LM. (2014). Sinorhizobium meliloti EmrR regulator is required for efficient colonization of Medicago sativa root nodules. Molecular Plant-Microbe Interactions 27:388-399. doi: 10.1094/MPMI-09-13-0284-R

[4] Ferreira AS, Silva IN, Oliveira VH, Becker JD, Givskov M, Ryan RP, Fernandes F, and Moreira LM. (2013). Comparative transcriptomic analysis of the Burkholderia cepacia tyrosine kinase bceF mutant reveals a role in tolerance to stress, biofilm formation and virulence. Applied and Environmental Microbiology. 79:3009-3020. doi: 10.1128/AEM.00222-13

[5] Ferreira AS, Silva IN, Oliveira VH, Cunha R, and Moreira LM. (2011). Insights into the role of extracellular polysaccharides in Burkholderia adaptation to different environments. Frontiers in Cellular and Infection Microbiology. 1:16, 1-9. doi: 10.3389/fcimb.2011.00016.

External Collaborators

Vaughn S. Cooper, School of Medicine, University of Pittsburgh, USA

James E.A. Zlosnik, Department of Pediatrics, University of British Columbia, Canada

Pedro M. Santos, Departamento de Biologia, Universidade do Minho, Portugal

Jörg D. Becker, Instituto Gulbenkian de Ciência, Portugal

Projects

ESCMID grant: “How do bacterial phosphotyrosine phosphatase proteins modulate host-pathogen interactions?”, European Society of Clinical Microbiology and Infectious Diseases, 2014-2015.

PTDC/QUI-BIQ/118260/2010: “KINASE – Phosphoproteomics in Burkholderia to assess the role of tyrosine phosphorylation in virulence determinants expression”, 2012-2015.

PTDC/BIA-MIC/113733/2009: “ROOT-INT – Role of a two-component regulatory system in the early interaction between Sinorhizobium meliloti and plant root hairs”, 2012-2015.