Role of Human Neutrophil Peptide–1 as a Possible Adjunct to Antituberculosis Chemotherapy

Abstract

We report the role of human neutrophil peptide (HNP)-1 as an adjunct to antituberculosis (anti-TB) drugs. The combination of HNP-1, isoniazid, and rifampicin was evaluated against Mycobacterium tuberculosis H(37)Rv in vitro, ex vivo, and in vivo, and synergism was observed on the basis of reductions in minimum inhibitory concentrations (MICs) of these agents. In vitro results revealed >1-log unit reductions even when HNP-1 and anti-TB drugs were used at 1/16 MICs. This combination was also found to be bactericidal against intracellular mycobacteria even at 1/8 MICs of HNP-1 and drugs. HNP-1 used in conjunction with anti-TB drugs resulted in significant clearance of bacterial load from lungs, liver, and spleen of infected, compared with control animals. The effective therapeutic dosage of drugs could be reduced to half by supplementing HNP-1 in the therapeutic schedule. These results clearly suggest that HNP-1 can be used as adjunct chemotherapy with conventional drugs against TB.

In VitroandIn VivoSynergistic Effects of Cryptdin 2 and Ampicillin against Salmonella

“…These results are in concordance with earlier reports suggesting a synergetic effect of antimicrobial peptides with ␤-lactam antibiotics (16,36). The most interesting finding of our study was that the addition of cryptdin 2 not only potentiated the effectiveness of ampicillin but also reduced the therapeutic dosage of both agents to half (from 5 g to 2.5 g per mouse of cryptdin 2 and from 16, 32, and 64 mg/kg to 8, 16, and 32 mg/kg of Amp) while maintaining the increased therapeutic efficacy, compared with that of the drugs alone, against experimental salmonellosis.…”

“…This can be attributed to an increased permeability of the Salmonella cell membrane created by cryptdin 2, thereby leading to an increased diffusion of Amp into the intracellular targets. These observations are consistent with previous studies pertaining to the synergetic actions of ␣-helical peptide p18, reproductive tract beta-defensins, HNP-1, magainin, cathelicidins, and several other novel cationic peptides with commonly used antibiotics against Escherichia coli, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter cloacae (7,16,32,36,37).…”

“…Combination therapy with antibiotics and defensins can therefore be used to increase the in vivo activity as well as to broaden the antimicrobial spectrum (13). Earlier, several AMPs were used in combination with conventional drugs against various bacteria, fungi, and viruses (10,16,21,31,42). However, until now, to the best of our knowledge, no information has been available on the combined activity of cryptdins and conventional anti-Salmonella drugs.…”

Defensins and Other Antimicrobial Peptides and a Role of Neutrophil Protein-Synthesing Function Disorders for Pathogenesis of Respiratory Diseases

“…Особенно актуальным представляется использование синтетических аналогов α-HD в ле-чении туберкулеза органов дыхания [61]. Изучается вопрос о применении стимуляторов синтеза HD, в т. ч. биологического, растительного и синтетичес-кого происхождения [31,[62][63][64][65].…”

Innate defences against methicillin‐resistant Staphylococcus aureus (MRSA) infection

“…Recently, α-defensins were reported to have an anti-HIV effect by inhibiting HIV replication, suggesting their clinical use as preventive and therapeutic agents [41,[50][51][52]. Other investigations for clinical use against microbial infection have been reported using animal models [53][54][55].…”