Effect of Hybrid Peptides of Cecropin A and Melittin in an Experimental Model of Bacterial Keratitis

Self Cite

115

121

In order to improve the leishmanicidal activity of the synthetic cecropin A-melittin hybrid peptide CA(1-7)M(2-9) (KWKLFKKIGAVLKVL-NH 2 ), a systematic study of its acylation with saturated linear fatty acids was carried out. Acylation of the N -7 lysine residue led to a drastic decrease in leishmanicidal activity, whereas acylation at lysine 1, in either the ␣ or the NH 2 group, increased up to 3 times the activity of the peptide against promastigotes and increased up to 15 times the activity of the peptide against amastigotes. Leishmanicidal activity increased with the length of the fatty acid chain, reaching a maximum for the lauroyl analogue (12 carbons). According to the fast kinetics, dissipation of membrane potential, and parasite membrane permeability to the nucleic acid binding probe SYTOX green, the lethal mechanism was directly related to plasma membrane permeabilization.

Section: Discussionmentioning

confidence: 83%

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confidence: 99%

N-Terminal Fatty Acid Substitution Increases the Leishmanicidal Activity of CA(1-7)M(2-9), a Cecropin-Melittin Hybrid Peptide

Chicharro

Granata

Lozano

et al. 2001

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115

121

“…In vivo experimental trials with synthetic antimicrobial peptides describe intravenous injection (3,9,16,28) and topical application (30,37). Oral administration of peptides in general is limited by the low level of bioavailability due to degradation by enzymes in the gastrointestinal tract and a lack of permeation through the intestinal mucosal membranes (15).…”

Section: Discussionmentioning

confidence: 99%

Activities of Synthetic Hybrid Peptides against Anaerobic Bacteria: Aspects of Methodology and Stability

Hedberg

Wade

et al. 2000

The increasing problem of antibiotic resistance among pathogenic bacteria requires development of new antimicrobial agents. One line of investigation is the synthesis of antimicrobial hybrid peptides. The aim of the present investigation was to determine the in vitro activities of 16 cecropin-melittin hybrid peptides (CAMEL analogues) against 60 anaerobic bacterial strains, to compare their activities with those of seven clinically used antimicrobial agents, and to compare different methods for anaerobic susceptibility testing of these peptides. The stability of one of the peptides, temporin B, with different stereoisomeric configurations was investigated in a fecal milieu. The CAMEL analogues showed antimicrobial activity against the anaerobic bacteria, with MICs ranging from 0.125 to 32 g/ml. The overall activities (the MICs at which 90% of isolates are inhibited) of the CAMEL analogues against anaerobic bacteria were mainly inferior to those of imipenem, clindamycin, and piperacillin but were equal to or superior to those of metronidazole, cefoxitin, ciprofloxacin, and chloramphenicol. The agarose dilution method was found to be an accurate method for the testing of large numbers of bacterial strains. The D isomer of temporin B was inactivated more slowly in feces than the L isomer. This study shows that the CAMEL analogues are potential agents for the treatment of anaerobic infections.

“…However, few studies have focused on the therapeutic potential of AMPs by topical application in bacterial keratitis, despite many investigations in other infectious diseases (12,17). The therapeutic efficacies of the synthetic peptides CA-M and COL-1 were investigated in a rabbit model of P. aeruginosa keratitis, and both peptides showed toxicity to the rabbit cornea and poor therapeutic efficacy (18,19). In a recent study, Oo et al demonstrated that combined bovine lactoferricin (B-Lfcin) and ciprofloxacin (CIP) treatment improved clinical outcomes and reduced the bacterial burden and myeloperoxidase (MPO) in infected corneas (20).…”

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confidence: 99%

Therapeutic Potential of the Antimicrobial Peptide OH-CATH30 for Antibiotic-Resistant Pseudomonas aeruginosa Keratitis

Liu

Xiang

et al. 2014

The therapeutic potential of antimicrobial peptides (AMPs) has been evaluated in many infectious diseases. However, the topical application of AMPs for ocular bacterial infection has not been well investigated. The AMP OH-CATH30, which was identified in the king cobra, exhibits potent antimicrobial activity. In this study, we investigated the therapeutic potential of OH-CATH30 for Pseudomonas aeruginosa keratitis. Ten isolates of P. aeruginosa from individuals with keratitis were susceptible to OH-CATH30 but not to cefoperazone, ciprofloxacin, gentamicin, and levofloxacin. The microdilution checkerboard assay showed that OH-CATH30 exhibited synergistic activity with ciprofloxacin and levofloxacin against antibiotic-resistant P. aeruginosa. Meanwhile, P. aeruginosa did not develop resistance to OH-CATH30, even after exposure at 0.5؋ the MIC for up to 25 subcultures. Furthermore, treatment with OH-CATH30, alone or in combination with levofloxacin, significantly improved the clinical outcomes of rabbit keratitis induced by antibiotic-resistant P. aeruginosa. Taken together, our data indicate that the topical application of OH-CATH30 is efficacious against drug-resistant P. aeruginosa keratitis. In addition, our study highlights the potential application of AMPs in treating ocular bacterial infections.