Page 40 - CIBERES-2015-eng

Research Groups
Group 2
Programme: Pneumonia / Host-Pathogen Interactions Lead Researcher: García López, Ernesto
Group members
STAFF MEMBERS: Ruiz García, Susana.
ASSOCIATED MEMBERS: Díez Martínez, Roberto | Doménech Lucas, Mirian | García González, Pedro |
Moscoso Naya, Miriam | Ramos Sevillano, Elisa | Yuste Lobo, José Enrique
Main lines of research
The development of invasive pneumococcal disease is preceded by the establishment of the “carrier state”, this is, the colonization of the human nasopharynx by Streptococcus pneumoniae (pneumococcus). Pneumococcal carriage takes place through the es- tablishment of a still largely unknown, host-pathogen interplay as well as by interactions with other bacte- ria colonizing the same habitat, such as non-type- able pneumococci, other streptococci of the mitis group, or pathogens like Haemophilus influenzae. Most of these interactions involve bacterial surface proteins on one hand, and cellular receptors and host defense mechanisms on the other. Cell wall hydro- lases (CWHs) are surface proteins produced by the pneumococcus that are directly involved in virulence. Thus, LytB and LytC are essential in nasopharyngeal colonization and help to avoid host immunity, while LytA triggers the release of other virulence factors, like the potent toxin pneumolysin and the neurami- nidase and plays an important role in pathogenesis
by releasing cell wall fragments that are markedly pro-inflammatory. All these CWHs are involved in bio- film formation. The role(s) in colonization of LytA and pneumolysin will be studied using biofilms (either mono or multispecies), cell cultures, and a mouse model of nasopharyngeal colonization. Besides, the impact of risky behaviors like smoking that facilitates bacterial colonization of the lungs and that con- tributes to the acute exacerbations in patients with chronic obstructive pulmonary disease will also be examined. Finally, one of the main aims of the pres- ent project is to develop prophylactic and therapeutic approaches to fight pneumococcal colonization. This will be performed using CWHs (enzybiotics) like Cpl-7 (a phage-coded enzyme of great antibacterial poten- tial), and novel drugs including several choline ana- logs and ceragenins. As for other objectives of this project, the efficacy of enzybiotics and novel drugs will be tested in vitro (planktonic as well as biofilm cultures) and in animal models of infection.
40 I Annual report 2015 I CIBERES