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.
Alpha-melanocyte-stimulating hormone (␣-MSH) is an endogenous neuropeptide that is known for its anti-inflammatory and antipyretic activities.We recently demonstrated that ␣-MSH possesses staphylocidal activity and causes bacterial membrane damage. To understand the role of its amino acid sequences in the staphylocidal mechanism, in the present study we investigated the antimicrobial activities of different fragments of ␣-MSH, i.e., ␣-MSH(6-13), ␣-MSH(11-13), and ␣-MSH(1-5), and compared them with that of the entire peptide. Our results showed that peptides containing the C-terminal region of ␣-MSH, namely, ␣-MSH(6-13) and ␣-MSH(11-13), efficiently killed >90% of both methicillin-sensitive and -resistant Staphylococcus aureus cells in the micromolar range and ϳ50% of these cells in the nanomolar range; their efficiency was comparable to that of the entire ␣-MSH, whereas the peptide containing the N-terminal region, ␣-MSH(1-5), was found to be ineffective against S. aureus. The antimicrobial activity of ␣-MSH and its C-terminal fragments was not affected by the presence of NaCl or even divalent cations such as Ca 2؉ and Mg 2؉ . Similar to the case for the parent peptide, ␣-MSH(6-13) and ␣-MSH(11-13) also depolarized and permeabilized Staphylococcus cells (ϳ70 to 80% of the cells were depolarized and lysed after 2 h of peptide exposure at micromolar concentrations). Furthermore, scanning and transmission electron microscopy showed remarkable morphological and ultrastructural changes on S. aureus cell surface due to exposure to ␣-MSH-based peptides. Thus, our observations indicate that C-terminal fragments of ␣-MSH retain the antimicrobial activity of entire peptide and that their mechanism of action is similar to that of full-length peptide. These observations are important and are critical in the rational design of ␣-MSH-based therapeutics with optimal efficacy.
The alpha-melanocyte stimulating hormone (α-MSH) is a neuropeptide belonging to the melanocortin family. It is well known for its anti-inflammatory and antipyretic effects and shares several characteristics with antimicrobial peptides (AMPs). There have been some recent reports about the direct antimicrobial activity of α-MSH against various microbes belonging to both fungal and bacterial pathogens. Similar to α-MSH's anti-inflammatory properties, its C-terminal residues also exhibit antimicrobial activity parallel to that of the entire peptide. This review is focused on the current findings regarding the direct antimicrobial potential and immunomodulatory mechanism of α-MSH and its C-terminal fragments, with particular emphasis on the prospects of α-MSH based peptides as a strong anti-infective agent.
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 (<10%). Nevertheless, the combination of α-MSH with RF and OX showed an enhanced killing by ∼45% and ∼70%, respectively, perhaps due to the membrane disrupting properties of α-MSH. The synergistic activity of α-MSH with antibiotics is encouraging, and promises to restore the lost potency of discarded antibiotics.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.