TY - JOUR
T1 - Activity and selectivity of histidine-containing lytic peptides to antibiotic-resistant bacteria
AU - Kharidia, Riddhi
AU - Tu, Zhigang
AU - Chen, Long
AU - Liang, Jun F.
PY - 2012/9
Y1 - 2012/9
N2 - Lytic peptides are a group of membrane-acting peptides that are active to antibiotic-resistant bacteria but demonstrate high toxicity to tissue cells. Here, we reported the construction of new lytic peptide derivatives through the replacement of corresponding lysine/arginine residues in lytic peptide templates with histidines. Resulting lytic peptides had the same lethality to antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus, but showed greatly improved selectivity to bacteria. When incubated with co-cultured bacteria and tissue cells, these histidine-containing lytic peptide derivatives killed bacteria selectively but spared co-cultured human cells. Membrane insertion and peptide-quenching studies revealed that histidine protonation controlled peptide interactions with cell membranes determined the bacterial selectivity of lytic peptide derivatives. Compared with parent peptides, lytic peptide derivatives bound to bacteria strongly and inserted deeply into the bacterial cell membrane. Therefore, histidine- containing lytic peptides represent a new group of antimicrobial peptides for bacterial infections in which the antibiotic resistance has developed.
AB - Lytic peptides are a group of membrane-acting peptides that are active to antibiotic-resistant bacteria but demonstrate high toxicity to tissue cells. Here, we reported the construction of new lytic peptide derivatives through the replacement of corresponding lysine/arginine residues in lytic peptide templates with histidines. Resulting lytic peptides had the same lethality to antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus, but showed greatly improved selectivity to bacteria. When incubated with co-cultured bacteria and tissue cells, these histidine-containing lytic peptide derivatives killed bacteria selectively but spared co-cultured human cells. Membrane insertion and peptide-quenching studies revealed that histidine protonation controlled peptide interactions with cell membranes determined the bacterial selectivity of lytic peptide derivatives. Compared with parent peptides, lytic peptide derivatives bound to bacteria strongly and inserted deeply into the bacterial cell membrane. Therefore, histidine- containing lytic peptides represent a new group of antimicrobial peptides for bacterial infections in which the antibiotic resistance has developed.
KW - Antibiotic resistance
KW - Antimicrobial peptides
KW - Lytic activity
KW - MRSA
KW - Selectivity
UR - http://www.scopus.com/inward/record.url?scp=84865980202&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865980202&partnerID=8YFLogxK
U2 - 10.1007/s00203-012-0810-5
DO - 10.1007/s00203-012-0810-5
M3 - Article
C2 - 22526264
AN - SCOPUS:84865980202
SN - 0302-8933
VL - 194
SP - 769
EP - 778
JO - Archives of Microbiology
JF - Archives of Microbiology
IS - 9
ER -