Page 51 - CIBERES-2015-eng

Most relevant scientific articles
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CaMPanero-rhoDes M.a., LLoBet e., BengoeChea J.a., so- Lis D.. Bacteria microarrays as sensitive tools for exploring pathogen surface epitopes and recognition by host recep- tors. RSC Advances. 2015;5(10):7173-7181.
toMas a., Lery L., regueiro v., Pérez-gutierrez C., Martínez v., Moranta D. et aL. Functional genomic screen identifies klebsiella pneumoniae factors implicated in blocking nuclear factor κB (NF-κB) signaling. Journal of Biológical Chemistry. 2015;290(27):16678-16697.
LLoBet e., Martínez-MoLiner v., Moranta D., DahLstroM K.M., regueiro v., toMasa a. et aL. Deciphering tissue-in- duced Klebsiella pneumoniae lipid a structure. Proceed- ings of the National Academy of Sciences of the United States of America. 2015;112(46):E6369-E6378.
euBa B., MoLeres J., segura v., viaDas C., Morey P., Moranta D. et aL. Genome expression profiling-based identification and administration efficacy of host-directed antimicrobial drugs against respiratory infection by non-
Cano v., MarCh C., insua J.L., aguiLo n., LLoBet e., Mo- ranta D. et aL. Klebsiella pneumoniae survives within macrophages by avoiding delivery to lysosomes. Cellular Microbiology. 2015;17(11):1537-1560.
Highlights
Our laboratory has developed a new method to purify and identify lipid A structure from a pathogen in vivo, directly from site of infection; without a subculture and/or enrichment step. This new method allowed us to identify that K. pneumoniae (KP) expresses a modified 2’-hydroxilated lipid A. This modification is dependent on the activation of the oxygenase en- zyme LpxO, in a phoPQ dependent manner (which is a KP two component system). The LpxO is ultimate- ly responsible for the 2’-hydroxylation of lipid A. This hydroxylated lipid A has lower immunogenicity than the non-hydroxylated structure that presents KP in a normal laboratory culture medium. In addition, this lipid A structure expressed during a lung infection confers to KP increased resistance to antimicrobi- al peptides present in lung; but further to colistin, which is one of the last options for treating infec- tions caused by multiresistant KP strains. Deleting lpxO gene, or inhibiting LpxO expression by deleting
typeable Haemophilus influenzae. Antimicrobial Agents and Chemotherapy. 2015;59(12):7581-7592.
some of the genes controlling its expression, reduc- es or completely removes the 2’-hydroxylation from lipid A and increases KP sensibility to colistin. We have analyzed a clinical isolates collection with KP strains resistant to multiple antibiotics and some of them resistant to colistin. These results suggest LpxO enzyme as a new therapeutic target to consid- er when dealing with KP strains resistant to colistin.
Lipid A analysis directly from infection site has also revealed that KP differentially modulates the lipid A structure depending on the organ that is infecting. These results highlight the ability of pathogens to change their lipid A structure depending on occu- pied niches; which in turn reinforces the need to explore new antimicrobial therapies, more specific to bacterial strain causing infection, and also to the specific organ that is infected.
Institution: Fundación de Investigación Sanitaria de las Islas Baleares Ramon Llull (FISIB) Contact: Hospital Universitario Son Espases · Ctra. Valldemossa, 79. 07010 Palma de Mallorca Tel.: 871 205 234 · E.mail: [email protected] · Website: http://www.idispa.es
CIBERES I Annual report 2015 I 51