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Lipidated Short Analogue of ?-Melanocyte Stimulating Hormone Exerts Bactericidal Activity against the Stationary Phase of Methicillin-Resistant Staphylococcus aureus and Inhibits Biofilm Formation.

ABSTRACT: Stationary phase Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), has been widely associated with many persistent infections as well as biofilm-associated infections, which are challenging due to their increasing antibiotic resistance. ?-Melanocyte stimulating hormone (?-MSH) is an antimicrobial peptide (AMP) with well-established potent activity against S. aureus , but little is known about its antimicrobial efficacy against the stationary phase of the bacteria. We investigated the in vitro activities of two palmitoylated analogues, Pal-?-MSH(6-13) and Pal-?-MSH(11-13), of the C-terminal fragments of ?-MSH against biofilm-producing strains of methicillin-sensitive S. aureus (MSSA) and MRSA. While both the peptides demonstrated anti-staphylococcal efficacy, Pal-?-MSH(11-13) emerged as the most effective AMP as palmitoylation led to a remarkable enhancement in its activity against stationary phase bacteria. Similar to ?-MSH, both the designed analogues were membrane-active and exhibited improved bacterial membrane depolarization and permeabilization, as further confirmed via electron microscopy studies. Of the two peptides, Pal-?-MSH(11-13) was able to retain its activity in the presence of standard microbiological media, which otherwise is a major limiting factor toward the therapeutic use of ?-MSH-based peptides. More importantly, Pal-?-MSH(11-13) was also highly effective in inhibiting the formation of biofilms. Furthermore, it did not lead to resistance development in MRSA cells even upon 18 serial passages at sub-MIC concentrations. These observations support the potential use of Pal-?-MSH(11-13) in the treatment of planktonic as well as sessile S. aureus infections.

SUBMITTER: Mumtaz S

PROVIDER: S-EPMC7658953 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Lipidated Short Analogue of α-Melanocyte Stimulating Hormone Exerts Bactericidal Activity against the Stationary Phase of Methicillin-Resistant Staphylococcus aureus and Inhibits Biofilm Formation.

Mumtaz Sana S Behera Swastik S Mukhopadhyay Kasturi K

ACS omega 20201026 44

Stationary phase Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), has been widely associated with many persistent infections as well as biofilm-associated infections, which are challenging due to their increasing antibiotic resistance. α-Melanocyte stimulating hormone (α-MSH) is an antimicrobial peptide (AMP) with well-established potent activity against S. aureus , but little is known about its antimicrobial efficacy against the stationary ph ...[more]

PMID: 33195893

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Project description:In an attempt to develop potent and non-toxic antimicrobial agent, the palmitoylated analogue of α-melanocyte stimulating hormone(11-13), Pal-α-MSH(11-13) was conjugated with gold nanoparticles (GNPs) for the first time and the efficacy of derived complex was investigated against two strains of Staphylococccus aureus. The GNPs were synthesized using tri-sodium citrate as reductant and Pal-α-MSH(11-13) was conjugated thereafter. The particles were characterised by UV-vis spectroscopy, transmission electron microscopy, dynamic light scattering, fourier transform infrared spectroscopy etc. Conjugation occurred via electrostatic interaction between anionic GNPs and cationic Pal-α-MSH(11-13). The zeta potential of GNP-Pal-α-MSH(11-13) was - 26.91, indicating its stability. The antibacterial activity was determined by minimal inhibitory concentration (MIC) and killing kinetics assay, whereas, inhibition of biofilm formation was studied by determining the biofilm biomass by crystal violet dye binding method, viability of biofilm-embedded cells by counting CFUs and metabolic activity by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The toxicity was analysed by hemolysis assay against murine RBCs and cytotoxicity against 3T3 fibroblasts. The MIC was 18 µM for GNP-Pal-α-MSH(11-13) and 12 µM for Pal-α-MSH(11-13). The killing kinetics and biofilm inhibition studies indicated the comparable efficacy of peptide before and after nano-conjugation. Importantly, the conjugation resulted in diminished toxicity, as evidenced by 0.29 ± 0.03% hemolysis and 100% viable fibroblasts at 72 µM compared to the Pal-α-MSH(11-13), showing 74.99 ± 1.59% hemolysis and 59.39 ± 1.06% viable fibroblasts. The nano-fabrication drastically reduced the peptide toxicity without compromising its antibacterial efficacy. The anionicity of the conjugate may be responsible for non-toxicity that makes them suitable for pharmaceutical applications.

Dataset Information

Lipidated Short Analogue of ?-Melanocyte Stimulating Hormone Exerts Bactericidal Activity against the Stationary Phase of Methicillin-Resistant Staphylococcus aureus and Inhibits Biofilm Formation.

Publications

Lipidated Short Analogue of α-Melanocyte Stimulating Hormone Exerts Bactericidal Activity against the Stationary Phase of Methicillin-Resistant <i>Staphylococcus aureus</i> and Inhibits Biofilm Formation.

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