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• d-M r, P H, B n, g e, M M, g P.. Improving the
Most relevant íeZArtíneZde AZuStAMAnteArcíAenéndeZArcíA
lethal effect of Cpl-7, a pneumococcal phage lysozyme with broad bactericidal acti-
scientific vity, by inverting the net charge of its cell wall-binding moduleAntimicrobial Agents

articles
and Chemotherapy. 2013;57:5355-5365.

• ruiZ FM, FernándeZ iS, lóPeZ-Merino l, lAgArterA l, kAltner H, MenéndeZ M, André S, So-

líS d, gABiuS H-J, roMero A. Fine-tuning of prototype chicken galectins: structure of
CG-2 and structure–activity correlationsActa Crystallographica Section D, Biologycal

Crystallography. 2013;D69(Pt 8):1655-1676.

• cArrero P, Ardá A, AlVAreZ M, doYAgüeZ eg, riVero-BucetA e, QueSAdA e, Prieto A, SolíS d,
cAMArASA MJ , PeréZ-PéreZ MJ, JiMéneZ-BArBero J, SAn-FéliX A. Differential Recognition of

Mannose-Based Polysaccharides by Tripodal Receptors Based on a Triethylbenzene
Scaffold Substituted with Trihydroxybenzoyl MoietiesEuropean Journal of Organic

Chemistry. 2013;1:65-76.

• erMAkoVA e, Miller Mc, neSMeloVA iV, lóPeZ-Merino l, BerBíS MA, neSMeloV Y, tkAcHeV YV,
l l, d VA, A S, c FJ, J-B J, S d, g H-J, M
AgArterAArAgAnndréAñAdAiMéneZArBeroolíSABiuSAYo
kH.. Lactose binding to human galectin-7 (p53-induced gene 1) induces long-range
effects through the protein resulting in increased dimer stability and evidence for

positive cooperativityGlycobiology. 2013;23 (5):508-523.

Highlights
After structurally and functionally characterizing the Cpl-7 endolysin from pneumococcal
bacteriophage Cpl-7, we have engineered a protein variant with 15 amino acid substi-

tutions and 18 negative charges less (Cpl-7S) whose exogenous killing activity against
Strepcotococcus pneumoniae, Streptococcus pyogenes and other pathogens is signifi-

cantly improved. Moreover, in the presence of 0.1% carvacrol, Cpl-7S also kills efficiently
Gram-negative bacteria, an effect not described previously. Cpl-7S bacteriolytic activity

was also validated in vivo using a new zebra-fish embryo model of infection. Cpl-7S and
its modification strategy, extensible to other murolytic enzymes, have been patented.

Characterization of glycan-mediated host-pathogen interactions was also initiated. Thus,

O-chain meditated binding of human galectins 3, 4, 8 and 9 to Klebsiella pneumoniae was
demonstrated, while a similar study on nontypeable Haemophilus influenzae revealed a

selective recognition of selected strains by human galectins 4, 8 and 9 whose biological
implications are been investigated. Development of designer’s bacterial microarrays has

shown to be central to both studies. In parallel, structure/function relation-ships in hu-

man galectins 3 and 4 are being investigated using different protein variants.
Results have generated so far four publications in scientific journal, 10 communications

to scientific congresses and specialized workshops, and one patent (Improved bacteri-

cidal antibiotics against Streptococus pneumoniae and other bacteria) in collaboration
with Dr. E. Garcias’s group of CIBERES.

ACTIVE PROJECTS:

• 2010-2012. Structural variability and substrate fine specificity of two families of bio-
medical relevant proteins. MICINN (BFU2009-10052)
13
20
• 2011-2013. Glycomics by High-throughput Integrated Technologies (UE; FP7- T
OR
HEALTH-2010-260600)
P
RE
• 2012-2015. Dynamic interactive nanosystems (EU; FP7-ITN-GA:289003) L
• A
2012-2015.BioinformaticsIntegrativeplatformforstructure-baseddrugdiscovery
NU
2 (CAM; S2010/BMD-2457)
N
A
• 2012-2016 . The Sugar Code: from (bio)chemical concept to clinics (UE; FP7-PEO- S /
PLE-2012-ITN-317297)
E
ER
• 2013-2015. Exploring exogenous and endogenous factors as tools for the control of B
CI
infectious and immune processes (MINECO; BFU2012-36825)

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