Martínez-Florensa, MarioCatalà, CristinaVelasco de Andrés, MaríaCañadas, OlgaFraile Ágreada, VíctorCasadó Llombart, SergiArmiger Borràs, NoeliaConsuegra-Fernández, MartaCasals, CristinaLozano Soto, Francisco2021-04-222021-04-222018-04-121664-3224https://hdl.handle.net/2445/176615Sepsis is an unmet clinical need constituting one of the most important causes of death worldwide, a fact aggravated by the appearance of multidrug resistant strains due to indiscriminate use of antibiotics. Host innate immune receptors involved in pathogen-associated molecular patterns (PAMPs) recognition represent a source of broad-spectrum therapies alternative or adjunctive to antibiotics. Among the few members of the ancient and highly conserved scavenger receptor cysteine-rich superfamily (SRCR-SF) sharing bacterial-binding properties there is CD6, a lymphocyte-specific surface receptor. Here, we analyze the bacterial-binding properties of three conserved short peptides (11-mer) mapping at extracellular SRCR domains of human CD6 (CD6.PD1, GTVEVRLEASW; CD6.PD2 GRVEMLEHGEW; and CD6.PD3, GQVEVHFRGVW). All peptides show high binding affinity for PAMPs from Gram-negative (lipopolysaccharide; Kd from 3.5 to 3,000 nM) and Gram-positive (lipoteichoic acid; Kd from 36 to 680 nM) bacteria. The CD6.PD3 peptide possesses broad bacterial-agglutination properties and improved survival of mice undergoing polymicrobial sepsis in a dose- and time-dependent manner. Accordingly, CD6.PD3 triggers a decrease in serum levels of both pro-inflammatory cytokines and bacterial load. Interestingly, CD6.PD3 shows additive survival effects on septic mice when combined with Imipenem/Cilastatin. These results illustrate the therapeutic potential of peptides retaining the bacterial-binding properties of native CD6.11 p.application/pdfengcc-by (c) Martínez Florensa, Mario et al., 2018http://creativecommons.org/licenses/by/3.0/esSepticèmiaImmunitatCisteïnaSepticemiaImmunityCysteineinfo:eu-repo/semantics/article6923902021-04-22info:eu-repo/semantics/openAccess29706953