Innovation in Respiratory Infections and Tuberculosis Diagnosis

José Domínguez
Cristina Prat-Aymerich

The research group is co-led by two Principal Investigators: Dr José Domínguez (MSc, PhD) is a "Miguel Servet" senior researcher and Dr. Cristina Prat-Aymerich (MD, PhD) is a medical microbiologist. This co-leadership gives to the group activity a complementary clinical-basic translational perspective.

We are located in the Institut d'Investigació Germans Trias i Pujol and Hospital Universitari Germans Trias i Pujol. We are affilated with the Universitat Autònoma de Barcelona (Genetics and Microbiology Departament, Biosciences Faculty) and the CIBERes net. The group is also part of the Clinical and Experimental Research Group (2014 SGR 1099).

The group is working in the field of the respiratory infections and tuberculosis, improving the understanding of the host-pathogen interaction, and exploring new approaches in the diagnosis and therapies.

Along with our close collaboration with the Microbiology department, our work is also done in collaboration and tight coordination with Pediatrics, Pneumology, Intensive Care and the Prevention Departments in the Hospital Universitary Germans Trias.  We also collaborate with national and international groups, belonging to Group #17 of the CIBER Enfermedades Respiratorias (CIBERes), in the research program of "Infectious respiratory diseases", particularly in the areas of "Tuberculosis" and "Host-pathogen interactions".

Research lines

Host-pathogen interaction

Regarding respiratory infections, our research focuses explore the microbial mechanisms of adaptation to the respiratory tract and related aspects of clinical presentation with phenotypic and genotypic traits of microorganisms; including bioinformatics approaches.  Research is mostly focused in Staphylococcus aureus but Pseudomonas aeruginosa and Haemophilus influenzae are also studied for aspects such as carrier status versus colonization versus infection in the respiratory tract and changes in bacterias due to factors such as hosting and antimicrobial treatment.  Also, similar work is carried out on bacteraemia and infections of skin and soft tissues.

These studies include phenotypic and genotypic characterization of isolates, correlation with the assignation of their pathogenic role and an approximation of phenotype, such as regulatory factors, quorum-sensing systems and their capacity for intracellular persistence, biofilm formation and secretion of toxins using molecular immunological techniques.   The objective is to identify differential factors that will allow the design of diagnostic tools to distinguish colonization from infection. The group is also participating in the ASPIRE consortium.

We use proteomic and metabolomics techniques to study the results of the host-microorganism interactions in clinical samples. In addition, we are starting to study the secretome and to use cytometry techniques as well.

Immune response characterization

We work to evaluate the diagnostic and prognostic importance of inflammation markers in infectious diseases.  We have extensive experience with procalcitonin, C-reactive protein, neopterin, pro-atrial natriuretic peptide and pro-adrenomedullin.  We also study the host immune response to different antigens specific of Mycobacterium tuberculosis to better characterize the latency state and to be able to find new biomarkers useful for identifying infected individuals with a higher risk of progressing to disease.  The group is involved in the VacTrain Constorium founded by the FP7 programme. This project is carried out using molecular and immunology techniques.  We also carry out studies on previous sensitization of the host to different non-tuberculous mycobacteria and their role in the diagnosis of tuberculosis infection.

Intracellular resistance model

We have set up a model of intracellular persistence in alveolar macrophages, which permits us to carry out trials for S. aureus protection with gentamicin and microscopy and transcriptome studies; and exploring the impact of tobacco smoke in the persistence of M. tuberculosis and its potential interaction with the anti-TB drugs.

Diagnostic technology innovation

We use molecular, metabolomics and immunology techniques for developing and testing diagnostic technologies, and for studying mutations associated with resistance to first and second line anti-tuberculosis drugs.  We are also carrying out differential molecular typing of M. tuberculosis strains for which we are now using whole genome sequencing. We are involved in two European consortiums with these purposes: "TB-prognosis" Consortium, funded by IRSES-FP7, and "StopTB/HIV at one" consortium, funded by EDCTP. We also participate in various trials carried out at the hospital for respiratory infections.

New therapeutic approaches

We are carrying out studies of novel therapeutic elements using susceptibility studies in vitro; and conventional S. aureus and M. tuberculosis drugs, by means of new administration, principally via nanoparticles, which release antibiotic at the site of infection, and are tested in the cellular model.  The TARMAC consortium, funded by CIBERES, CIBER-BBN and SEPAR, is developing this study.