Abstract
Antimicrobial peptides form part of the innate immune response and play a vital role in host defense against pathogens. Here we report a new antimicrobial peptide belonging to the cathelicidin family, cathelicidin-MH (cath-MH), from the skin of Microhyla heymonsivogt frog. Cath-MH has a single α-helical structure in membrane-mimetic environments and is antimicrobial against fungi and bacteria, especially Gram-negative bacteria. In contrast to other cathelicidins, cath-MH suppresses coagulation by affecting the enzymatic activities of tissue plasminogen activator, plasmin, β-tryptase, elastase, thrombin, and chymase. Cath-MH protects against lipopolysaccharide (LPS)- and cecal ligation and puncture-induced sepsis, effectively ameliorating multiorgan pathology and inflammatory cytokine through its antimicrobial, LPS-neutralizing, coagulation suppressing effects as well as suppression of MAPK signaling. Taken together, these data suggest that cath-MH is an attractive candidate therapeutic agent for the treatment of septic shock.
Highlights
Septic shock represents an unbalanced host response to infection and remains a major cause of death in intensive care units in developed countries (Huang et al, 2019)
Based on PCR-based cDNA cloning, a novel Antimicrobial peptides (AMPs) was obtained from the cDNA library derived from the skin of M. heymonsivogt frogs
NCBI Basic Local Alignment Search Tool (BLAST) analysis and multisequence alignment revealed that the cath-MH precursor had high sequence similarity with other members of the cathelicidin family (Figure 1B), containing four cysteine residues at the end of the cathelin domain and a highly variable C-terminal mature region
Summary
Septic shock represents an unbalanced host response to infection and remains a major cause of death in intensive care units in developed countries (Huang et al, 2019). Severe sepsis is associated with tissue damage, abnormal coagulation and immune responses, and ‘cytokine storms’ triggered by inflammatory factors (Huang et al, 2019). Lipopolysaccharide (LPS; endotoxin) is the main component of the outer membrane of Gram-negative bacteria which, as one of the most potent natural immunostimulatory compounds, plays a crucial role in sepsis and septic shock through hyperactivation of the innate immune system (Salomao et al, 2012). Cathelicidins are derived from precursor proteins consisting of an N-terminal signaling peptide and a highly conserved cathelin domain in
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