Research lines

Host-pathogen interaction

In terms of respiratory infections, our research focuses on exploring the microbial mechanisms of adaptation to the respiratory tract and related aspects of clinical presentation with phenotypic and genotypic traits of microorganisms; including immunologic, metabolomic and bioinformatic approaches.  Research is mostly focused in Staphylococcus aureus but we also study Pseudomonas aeruginosa, Haemophilus influenzae and Streptococcus pneumoniae to explore the shift from carriage to infection.  Topics 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 COMBACTE Network.

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 to 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 has been involved in the VacTrain Consortium 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 persistance model

We have set up a cell infection model using alveolar macrophages to assess S. aureus intracellular survival strategies using gentamycin protection assay, immunofluorescence and transcriptomic analysis. The model can be adapted to other microorganisms, such as M. tuberculosis and Pseudomonas aeruginosa and cell lines, including human monocytes and lung epithelial cells. In addition, we are also exploring the impact of tobacco smoke (standard and e-cigarettes) and diesel exhaust particles in M. tuberculosis intracellular persistence mechanisms and their potential interaction with the activity of anti-TB drugs. The development of a 3D in vitro tissue model of human alveoli will allow us to get a more accurate description of the interaction during lung infections.

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 were involved in two European consortiums with these purposes: "TB-prognosis" Consortium, funded by IRSES-FP7, and "StopTB/HIV at one" consortium, funded by EDCTP. Currently we are coordinators of the INNOVA4TB consortium an EU project RISE-H2020.

We have developed, evaluated and optimized several diagnostic technologies also for other bacterial (Legionella pneumophila, S. pneumoniae, Bordetella pertussis, and Mycoplasma pneumoniae), fungal (Aspergillus spp) and viral respiratory tract infections (Metapneumovirus, Influenza virus, Syncytial respiratory virus, etc.)

Novel therapeutic approaches

We are evaluating novel drug delivery systems based on the use of antimicrobial loaded nanoparticles for the treatment of S. aureus and M. tuberculosis infections. Nanoparticles are designed to reach infected cells and thus co-localize with intracellular bacteria. Different routes of administration are being explored, with the final objective of improving delivery in lung tissue. We are comparing the efficacy of free and encapsulated drugs using different in-vitro susceptibility tests and cell infection assays in previous steps before their evaluation in a murine model.

Current Research Projects

Tuberculosis: Development of new diagnostic methods, new host-direct therapies and understanding the impact of extrinsic factors in modulating inflammation (INNOVA2)

Code: PI19/01408
Principal Investigator: José Antonio Domínguez Benítez 
Start Date: 2020
End Date: 2023

Pneumococcal pNeumonia Epidemiology, Urine serotyping, and Mental Outcomes. The PnEUmo Study in Europe (PNEUMO)

Code: 820755
Central PI: Jan Kluytmans, Scientific Coordinator: Cristina Prat Aymerich, Principal Investigators HUGTiP: Alicia Lacoma and Fernando Armestar 
Start Date: 2020
End Date: 2023

Impact of the use of antibiotics on the adaptation of Staphylococcus aureus to the lower respiratory tract: new diagnostic and therapeutic strategies

Code: PI 17/01139
Principal Investigator: Cristina Prat Aymerich 
Start Date: 2018
End Date: 2020

Innovation for TB. INNOVA4TB

Code: H2020-RISE-2018
Principal Investigator: José Antonio Domínguez Benítez (Coordinating institution)  
Start Date: 2019
End Date: 2022

Caracterización de receptores celulares "homing" y estudio del papel de las células B reguladoras en el diagnóstico de la tuberculosis

Code: 16/025
Principal Investigator: Irene Latorre  
Start Date: 2017
End Date: 2020

Estudio clínico-experimental del impacto del humo del tabaco y del vapor de los cigarrillos electrónicos en las interacciones huésped-patógeno en las infecciones respiratorias

Code: 16/024
Principal Investigator: José Antonio Domínguez Benítez 
Start Date: 2017
End Date: 2020

Desarrollo de una técnica point-of-care basada en el metaboloma urinario para el diagnóstico de la tuberculosis y la monitorización del tratamiento

Code: DTS18/00092
Principal Investigator: José Antonio Domínguez Benítez
Start Date: 2019
End Date: 2021

Caracterización de receptores celulares "homing" y estudio del papel de las células B reguladoras en el diagnóstico de la tuberculosis

Code: PI18/00411
Principal Investigator: Irene Latorre
Start Date: 2019
End Date: 2021

RESPINNOVA: Toward improving the clinical management of respiratory infectious diseases by host-pathogen interplay innovative. Valoració ANEP 12/15

Code: CIBERES 19-21/08
Principal Investigator: J. Garmendia
Start Date: 2019
End Date: 2021

Tackling Tuberculosis Global challenges

Code: CIBERES 19-21/07
Principal Investigator: J. A Aínsa
Start Date: 2019
End Date: 2021

Bronchiectasias heterogeneity and susceptibility to infection: host-microbiome interactions and its predictive power in clinical practice

Code: CIBERES intramural projects
Principal Investigator: A Marín
Start Date: 2019
End Date: 2020

Multi-centre EuRopean study of MAjor Infectious Disease Syndromes (MERMAIDS) - Acute Respiratory Infections (MERMAIDS ARI) 2.0. ClinicalTrials.gov identifier NCT04364711 

Code: ClinicalTrials.gov identifier NCT04364711
Sponsor Europe: UMC Utrecht PI: Patricia Bruijning. Coordinating investigator: CPrat 
PI HUGTiP: Zoran Stojanovic and Carlos Rodrigo
Part of the Consortium Rapid European COVID19 Research Response (RECOVER)
Funding: European Union's Horizon 2020 research and innovation programme under grant agreement No 101003589
Consortium coordinator: Herman Goossens

Start Date: 2020
End Date: 2022

BCG vaccination to Reduce the impact of COVID-19 in healthcare workers following Coronavirus Exposure (BRACE) Trial

Code:HREC/protocol no: 62586 NCT04327206. EUDRACT 2020-002503-19 
Chief PI: Nigel Curtis, Murdoch's Children Research Institute Melbourne Australia, Sponsor Europe: UMC Utrecht PI Europe: Marc Bonten
Coordinating investigator (Netherlands and Spain): C Prat
PI HUGTiP: Antoni Rosell Gratacós

Start Date: 2020
End Date: 2022