The Gram-positive Staphylococcus aureus is a major human pathogen [1, 2], and the increasing prevalence of methicillin-resistant S. aureus (MRSA) in hospitals and communities, both human and animal has led to a demand for new agents that could be used to decrease the spread of this bacterium. Anti-microbial peptides (AMPs) are essential components of innate immunity in humans and other higher organisms, contributing to our first line of defense against infection. The AMPs belonging to the cathelicidin family are a large group of peptides ranging from 12 to 80 amino acid residues in length. LL-37 [3] is the 37-residue human cathelicidin, which represents one of the most studied AMP showing a broad-spectrum anti-microbial activity against Gram-negative and Gram-positive bacteria, including S. aureus [3]. However, MRSA strains appear to be less sensitive to LL-37 [4], demonstrating the need to identify more effective AMPs. Thus, we have developed two synthetic cathelicidin peptides, hCath-D and NaCath-D, from human and snake (Naja atra), respectively, and tested their anti-microbial activity against MRSA. The peptides were modified to possibly increase antimicrobial potency taking into account the appropriate balance among the total net charge, amphipathicity and hydrophobicity. Interestingly, they showed a significant potential antimicrobial activity (Boman index: 3.0 and 2.54, GRAVY values: 0.22 and -1.58, total net charge: +5 and +8, for hCath-D and NaCath-D, respectively), when submitted to the predictive tool available at the Antimicrobial Peptide Database v2.34 (APD2; http://aps.unmc.edu/A P/main.php).
New synthetic cathelicidin peptides with anti-microbial activity against methicillin-resistant Staphylococcus aureus
Balestrieri M;
2015
Abstract
The Gram-positive Staphylococcus aureus is a major human pathogen [1, 2], and the increasing prevalence of methicillin-resistant S. aureus (MRSA) in hospitals and communities, both human and animal has led to a demand for new agents that could be used to decrease the spread of this bacterium. Anti-microbial peptides (AMPs) are essential components of innate immunity in humans and other higher organisms, contributing to our first line of defense against infection. The AMPs belonging to the cathelicidin family are a large group of peptides ranging from 12 to 80 amino acid residues in length. LL-37 [3] is the 37-residue human cathelicidin, which represents one of the most studied AMP showing a broad-spectrum anti-microbial activity against Gram-negative and Gram-positive bacteria, including S. aureus [3]. However, MRSA strains appear to be less sensitive to LL-37 [4], demonstrating the need to identify more effective AMPs. Thus, we have developed two synthetic cathelicidin peptides, hCath-D and NaCath-D, from human and snake (Naja atra), respectively, and tested their anti-microbial activity against MRSA. The peptides were modified to possibly increase antimicrobial potency taking into account the appropriate balance among the total net charge, amphipathicity and hydrophobicity. Interestingly, they showed a significant potential antimicrobial activity (Boman index: 3.0 and 2.54, GRAVY values: 0.22 and -1.58, total net charge: +5 and +8, for hCath-D and NaCath-D, respectively), when submitted to the predictive tool available at the Antimicrobial Peptide Database v2.34 (APD2; http://aps.unmc.edu/A P/main.php).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
