Impact of mobile genetic elements and horizontal gene transfer on bacteia-host adaptation: a genomics view

Staphylococcus aureus, Streptococcus pneumonia, Moraxella catarrhalis, and nontypable Haemophilus influenzae (NTHi) strains contribute to chronic obstructive pulmonary disease (COPD), which according to WHO is considered to become a significant life-threatening risk factor for patients suffering from chronic bronchitis. NTHi are Gram negative bacteria and are defined by heterogeneous surface antigens and a lack of capsule. They are responsible for chronic and acute inflammation of the upper respiratory track, particularly for otitis media in children. Variation of antigenic structures and genetic variability is a hallmark of NTHi strains. The genome heterogeneity of NTHi isolates indicates a variable intraspecies genetic pool. Variation of differential expression patterns in combination with loss and gain of genetic information facilitates host invasion, adaptation and diversification of NTHi population. A specific objective of this project is to characterize genetic exchange in colonizing populations of NTHi strains. The requirement to approach such objective is to determine the magnitude of gene exchange, to identify horizontally transferred genetic information, and to characterize the underlying molecular transfer mechanisms. We propose to characterize competence development, genetic transfer, and OMVs used for DNA-transfer, and antigen delivery. The partners of the consortium will work in a cooperative and supportive way. The synergies of the partners will involve: (i) the use of common experience in the biology of mobile genetic elements; (ii) the utilization of the established sequencing platform at the Institut Pasteur; (iii) the exchange of in vivo models to study horizontal gene transfer in vivo; (iv) the comparative analysis of different strategies of adaptation in the same niche; (v) the exchange and extension of genetic tools and technical knowledge established in the groups.

Within the ERA-NET PathoGenoMic we worked on non-typeable Haemophilus influenzae (NTHi) strains and have characterized mechanisms of horizontal gene transfer (HGT), competence development, persistence of bacterial colonization in the nasopharynx in mice, and mechanisms of serum resistance in NTHi. The established results of these projects comprise the establishment of a colonization- and in vivo transformation model, which indicates the HGT in the mice seems to be not higher then observed under laboratory conditions. Surprisingly, we could not demonstrate capsule gene transfer between encapsulated and NTHi isolates, indicating that capsule gene transfer seems only to take place among the established six capsule expressing subspecies. Indicating an evolutionary close development of encapsulated strains, and which may let expect no capsule gene transfer into NTHi population. We further showed the importance of L-lactate as signal substrate for persistent colonization, and characterized serum resistance mechanisms in a freshly isolated clinical NTHi isolate. In coordination with the consortium partners we have concentrated on the mechanisms of HGT and also performed genome sequencing of our model strains within the consortium. Finally, and important for health and society, it is to mention that NTHi bacteria are pathogens of humans and are widely responsible for chronic inflammation of the upper respiratory tract that contribute to chronic obstructive pneumonial disease (COPD). COPD is considered by the WHO to be a significant life-threatening risk factor for patients suffering from chronic bronchitis.