Page 25 - CIBERES-2015-eng

Host-Pathogen Interactions
COORDINATOR: DR . JUNKAL GARMENDIA
In 2015 our work focussed on analysing the mo- lecular mechanisms used by a panel of respira- tory pathogens of great healthcare relevance for manipulating host functions in their own benefit and evading the immune system. This informa- tion has enabled identifying host-pathogen inter- actions, as well as designing and evaluating new
Scientific Programmes
5. We determined the immune-modulation ef- fect of anionic phospholipids on alveolar mac- rophages and pneumocytes in the presence of bacterial lipopolysaccharide, syncytial respira- tory virus or Haemophilus influenzae (Hi) (G1, 19, 32).
6.We developed design microarrays for the
antimicrobial agents. To sum up:
1. In the fight against multi-resistant bacteria we proved the in vitro and in vivo bactericide effectiveness of auranofin (a drug against rheumatoid arthritis), dendrimers of esters of bicyclic amines and new chimeric endolysins based on endolysins of Streptococcus pneu- moniae phages (G2 and 34).
2. We assessed a panel of strains of Staphylo- coccus aureus isolated from patients subject to mechanic ventilation in an alveolar mac- rophage model of infection, displaying dif- ferences in the intracellular dynamics of the infection, and established systems for detec- tion of virulence factors of S. aureus in clinical samples and of evaluation of the intracellular activity of drugs encapsulated in nanoparti- cles (G17).
3. We determined the synergic microbicide ac- tion of proteins SP-BN and SP-A, present in the alveolar fluid, against Klebsiella pneumo- niae (Kpn), and showed that its therapeutic administration reduces infection and boosts immune response against Kpn. We deter- mined the immune-modulator role of SP-A in classic and alternative activation of alveolar macrophages (G1).
4. We characterised the PhoP- WhiB6 transcrip- tional network in the context of the expression and secretion of ESAT-6 in M. tuberculosis, identified a new non-coding antisense RNA to gene ideR, and optimised a system for quan- tifying c-di-AMP in M. tuberculosis, which shows a greater production of c-di-AMP asso- ciated with phoP (G9) mutation.
study of receptors on the surface of live bacte- ria used in the characterisation of Hi glycosyl- ation profiles and their recognition by lectins of the immune system (G19 and 34).
7. We characterised that a small amount of large deletions of the segments of the viral genoma in the influenza virus virions constitutes a fac- tor of pathogenicity for the human population (G32).
8. We determined the atomic structure of protein F of the human metapneumovirus in its post- fusion conformation, displaying a high degree of homology with protein F of the human syn- cytial respiratory virus. In view of the cross-re- activity between both proteins, we obtained chimerical proteins to induce an immune re- sponse against the two virus (G32).
9. We provided the first evidence of Hi adaptation in vivo, defining for Hi an intracellular niche in the human respiratory epithelium and a pan- el of strategies of cell subversion used by the bacteria to access this niche; we displayed the antimicrobial potential of pharmacological in- terference of eukaryotic targets and took part in the first study to define the effect of gluco- corticoids in the Hi transcriptome during lung infection (G19).
CIBERES I Annual report 2015 I 25