Seminar

Bacterial pathogen adaptation to the human airways: from mechanistics to therapeutics

Juncal Garmendia

Chronic obstructive pulmonary disease (COPD) and lower respiratory tract infections (LRTI) are in top positions in the WHO ranking of causes of death worldwide. COPD lower airways are chronically infected by pathogens. Up to 1/3 of COPD patients suffer at least one acute exacerbation per year, often of infectious nature and clinically considered as LRTI. LRTI are within the most common reasons for medical consultation and antibiotic prescription, often caused by bacteria with recalcitrant lifestyles including intracellular life, biofilm growth or antibiotic tolerance. Haemophilus influenzae (Hi) is an important bacterial cause of LRTI, associated with COPD exacerbations and detected in 30% stable COPD patients. It is well adapted to the human airways by persisting within epithelia (as a facultative intracellular) or within biofilms, and it is included in the WHO Global Priority List of pathogens for which the traditional direct-acting antibiotic approach is limited by antimicrobial resistance (AMR). Our work, with a strong multidisciplinary dimension where imaging, multi-omics, and computation are key tools supporting our molecular-cellular microbiology expertise, focuses on specific challenges posed by respiratory patients undergoing persistent infections by H. influenzae, and aims to identify useful targets for therapeutic development. In this context, we address the biological significance and underlying mechanisms of a range of adaptive traits. Our current efforts are dedicated to decipher (i) posttranscriptional and epigenomic regulatory elements of bacterial gene expression; (ii) bacterial metabolic networks contributing to fitness during infection, (iii) antibiotic escape by the means of heteroresistance, tolerance and/or persistence development, (iv) dynamics of polymicrobial infections within the lower airways.