Combination of alpha-melanocyte stimulating hormone with conventional antibiotics against methicillin resistant Staphylococcus aureus

• Published in: PloS one 2013-09, Vol.8 (9), p.e73815
• Main Authors: Singh, Madhuri, Gadepalli, Ravisekhar, Dhawan, Benu, Mukhopadhyay, Kasturi
• Format: Article
• Language: English
• Subjects: 3T3 Cells; alpha-MSH - pharmacology; Aminoglycosides; Analysis; Animals; Anti-Bacterial Agents - pharmacology; Antibiotics; Antimicrobial agents; Bacteria; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Cell Survival - drug effects; Ciprofloxacin; Ciprofloxacin - pharmacology; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA, Bacterial - genetics; DNA, Bacterial - metabolism; Dose-Response Relationship, Drug; Drug dosages; Drug resistance; Drug Synergism; Environmental science; Fibroblasts - cytology; Fibroblasts - drug effects; Gentamicin; Gentamicins - pharmacology; Hemolysis - drug effects; Humans; Melanocyte stimulating hormone; Methicillin; Methicillin-Resistant Staphylococcus aureus - drug effects; Methicillin-Resistant Staphylococcus aureus - genetics; Methicillin-Resistant Staphylococcus aureus - growth & development; Mice; Microbial drug resistance; Microbial Sensitivity Tests - methods; Microbial Viability - drug effects; Microbial Viability - genetics; Minimum inhibitory concentration; Oxacillin; Oxacillin - pharmacology; Pathogens; Peptides; Perturbation; Protein biosynthesis; Protein synthesis; Ribonucleic acid; Rifampin; Rifampin - pharmacology; RNA; RNA polymerase; RNA, Bacterial - genetics; RNA, Bacterial - metabolism; Staphylococcus aureus; Staphylococcus aureus infections; Staphylococcus infections; Supplements; Tetracycline - pharmacology; Transcription
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0073815

Our previous studies revealed that alpha-melanocyte stimulating hormone (α-MSH) is strongly active against Staphylococcus aureus (S. aureus) including methicillin resistant S. aureus (MRSA). Killing due to α-MSH occurred by perturbation of the bacterial membrane. In the present study, we investigated the in vitro synergistic potential of α-MSH with five selected conventional antibiotics viz., oxacillin (OX), ciprofloxacin (CF), tetracycline (TC), gentamicin (GM) and rifampicin (RF) against a clinical MRSA strain which carried a type III staphylococcal cassette chromosome mec (SCCmec) element and belonged to the sequence type (ST) 239. The strain was found to be highly resistant to OX (minimum inhibitory concentration (MIC) = 1024 µg/ml) as well as to other selected antimicrobial agents including α-MSH. The possibility of the existence of intracellular target sites of α-MSH was evaluated by examining the DNA, RNA and protein synthesis pathways. We observed a synergistic potential of α-MSH with GM, CF and TC. Remarkably, the supplementation of α-MSH with GM, CF and TC resulted in ≥ 64-, 8- and 4-fold reductions in their minimum bactericidal concentrations (MBCs), respectively. Apart from membrane perturbation, in this study we found that α-MSH inhibited ≈ 53% and ≈ 47% DNA and protein synthesis, respectively, but not RNA synthesis. Thus, the mechanistic analogy between α-MSH and CF or GM or TC appears to be the reason for the observed synergy between them. In contrast, α-MSH did not act synergistically with RF which may be due to its inability to inhibit RNA synthesis (