Combination of Alpha-Melanocyte Stimulating Hormone with Conventional Antibiotics against Methicillin Resistant Staphylococcus aureus

Singh, Madhuri; Gadepalli, Ravisekhar; Dhawan, Benu; Mukhopadhyay, Kasturi

doi:10.1371/journal.pone.0073815

Cited by 12 publications

(36 citation statements)

References 55 publications

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“…Studies are being conducted in our laboratory to test this hypothesis. Such a strategy could be immensely promising in the current scenario of continuous emergence of resistant microorganisms and antibiotic crisis [ 31 , 32 ]. Oxidative stress and inflammation often go together with bacterial infections [ 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Bactericidal Activity of Curcumin I Is Associated with Damaging of Bacterial Membrane

et al. 2015

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Curcumin, an important constituent of turmeric, is known for various biological activities, primarily due to its antioxidant mechanism. The present study focused on the antibacterial activity of curcumin I, a significant component of commercial curcumin, against four genera of bacteria, including those that are Gram-positive (Staphylococcus aureus and Enterococcus faecalis) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa). These represent prominent human pathogens, particularly in hospital settings. Our study shows the strong antibacterial potential of curcumin I against all the tested bacteria from Gram-positive as well as Gram-negative groups. The integrity of the bacterial membrane was checked using two differential permeabilization indicating fluorescent probes, namely, propidium iodide and calcein. Both the membrane permeabilization assays confirmed membrane leakage in Gram-negative and Gram-positive bacteria on exposure to curcumin I. In addition, scanning electron microscopy and fluorescence microscopy were employed to confirm the membrane damages in bacterial cells on exposure to curcumin I. The present study confirms the broad-spectrum antibacterial nature of curcumin I, and its membrane damaging property. Findings from this study could provide impetus for further research on curcumin I regarding its antibiotic potential against rapidly emerging bacterial pathogens.

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Section: Discussionmentioning

confidence: 99%

Bactericidal Activity of Curcumin I Is Associated with Damaging of Bacterial Membrane

et al. 2015

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“…A number of host-derived peptides or their mimics with direct bactericidal activity along with other essential cellular targets present their candidature towards optimization as antibacterial leads 3 37 38 . Our previous studies have shown that the neuropeptide α-MSH and its smaller fragments i.e., α-MSH(6–13) and α-MSH(11–13) have potent activity against S. aureus , MRSA and several clinical strains of S. aureus in micromolar concentration range 22 23 24 25 26 . Recently, in an elegant attempt to modify the activity of α-MSH(6–13), Grieco et al .…”

Section: Discussionmentioning

confidence: 99%

“…In the present work minimum inhibitory concentration (MIC) using broth micro-dilution technique following Clinical Laboratory Standards Institute (CLSI) guidelines could not be determined since similar to α-MSH the antibacterial activity of designed peptides got abolished in nutrient media used for the experiment 24 25 .…”

Section: Methodsmentioning

confidence: 99%

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Enhanced Cationic Charge is a Key Factor in Promoting Staphylocidal Activity of α-Melanocyte Stimulating Hormone via Selective Lipid Affinity

Singh

Joshi

Mumtaz

et al. 2016

Sci Rep

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The steady rise in antimicrobial resistance poses a severe threat to global public health by hindering treatment of an escalating spectrum of infections. We have previously established the potent activity of α-MSH, a 13 residue antimicrobial peptide, against the opportunistic pathogen Staphylococcus aureus. Here, we sought to determine whether an increase in cationic charge in α-MSH could contribute towards improving its staphylocidal potential by increasing its interaction with anionic bacterial membranes. For this we designed novel α-MSH analogues by replacing polar uncharged residues with lysine and alanine. Similar to α-MSH, the designed peptides preserved turn/random coil conformation in artificial bacterial mimic 1,2-dimyristoyl-sn-glycero-3-phosphocholine:1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (7:3, w/w) vesicles and showed preferential insertion in the hydrophobic core of anionic membranes. Increased cationic charge resulted in considerable augmentation of antibacterial potency against MSSA and MRSA. With ~18-fold better binding than α-MSH to bacterial mimic vesicles, the most charged peptide KKK-MSH showed enhanced membrane permeabilization and depolarization activity against intact S. aureus. Scanning electron microscopy confirmed a membrane disruptive mode of action for KKK-MSH. Overall, increasing the cationic charge improved the staphylocidal activity of α-MSH without compromising its cell selectivity. The present study would help in designing more effective α-MSH-based peptides to combat clinically relevant staphylococcal infections.

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“…To determine the antimicrobial activity of FI3, 2 × 10 6 MSSA cells of mid exponential phase were taken as described elsewhere (26). The cells were incubated with varying concentration of FI3 i.e.…”

Section: Cell Viability Assaymentioning

confidence: 99%

Fungal-derived xenobiotic exhibits antibacterial and antibiofilm activity against <i>Staphylococcus aureus </i>

Kumar

Kaushal³

et al. 2018

DD&T

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Staphylococcus aureus is an opportunistic pathogen, responsible for superficial and invasive infections both in nosocomial and community-acquired settings. The incidences of infection have become more problematic attributable to emerging drug resistance and biofilm formation. These challenges suggest the need for new antimicrobial agents against S. aureus. In present work, we purified a fungal xenobiotic (FI3) which elicits a potent antimicrobial activity against a list of tested microbes including methicillin sensitive (MSSA) and methicillin resistance (MRSA) S. aureus. The cell growth of MSSA and MRSA were completely ceased with the 1× minimum inhibitory concentration (MIC); 32 µg/mL and 128 µg/mL, respectively. The cell viability severely decreased within 90 min, due to disturbance of membrane homeostasis. This bactericidal effect was enhanced at lower pH (pH 4) with a speculation to retain positive charge. The FI3 potently disrupts biofilm adherence at 64 µg/mL and found to be a safe with no toxic effect on mammalian tissue. FI3 also leads to increase the potency of tested antibiotics. Taken together, we established that FI3 has a potent antimicrobial activity against tested microbes and safer to human tissue. It may be proven a leading molecule for the treatment of bacterial infections.

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Combination of Alpha-Melanocyte Stimulating Hormone with Conventional Antibiotics against Methicillin Resistant Staphylococcus aureus

Cited by 12 publications

References 55 publications

Bactericidal Activity of Curcumin I Is Associated with Damaging of Bacterial Membrane

Bactericidal Activity of Curcumin I Is Associated with Damaging of Bacterial Membrane

Enhanced Cationic Charge is a Key Factor in Promoting Staphylocidal Activity of α-Melanocyte Stimulating Hormone via Selective Lipid Affinity

Fungal-derived xenobiotic exhibits antibacterial and antibiofilm activity against <i>Staphylococcus aureus </i>

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