Madhuri Singh

Bio: Madhuri Singh is an academic researcher from Jawaharlal Nehru University. The author has contributed to research in topics: Staphylococcus aureus & Antimicrobial peptides. The author has an hindex of 7, co-authored 10 publications receiving 451 citations.

Bactericidal activity of curcumin I is associated with damaging of bacterial membrane.

Abstract: 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: An Emerging Anti-Inflammatory Antimicrobial Peptide

Abstract: 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.

C-terminal amino acids of alpha-melanocyte stimulating hormone are requisite for its antibacterial activity against Staphylococcus aureus

Abstract: Alpha-melanocyte-stimulating hormone (α-MSH) is an endogenous neuropeptide that is known for its anti-inflammatory and antipyretic activities. We recently demonstrated that α-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 α-MSH, i.e., α-MSH(6-13), α-MSH(11-13), and α-MSH(1-5), and compared them with that of the entire peptide. Our results showed that peptides containing the C-terminal region of α-MSH, namely, α-MSH(6-13) and α-MSH(11-13), efficiently killed >90% of both methicillin-sensitive and -resistant Staphylococcus aureus cells in the micromolar range and ∼50% of these cells in the nanomolar range; their efficiency was comparable to that of the entire α-MSH, whereas the peptide containing the N-terminal region, α-MSH(1-5), was found to be ineffective against S. aureus. The antimicrobial activity of α-MSH and its C-terminal fragments was not affected by the presence of NaCl or even divalent cations such as Ca2+ and Mg2+. Similar to the case for the parent peptide, α-MSH(6-13) and α-MSH(11-13) also depolarized and permeabilized Staphylococcus cells (∼70 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 α-MSH-based peptides. Thus, our observations indicate that C-terminal fragments of α-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 α-MSH-based therapeutics with optimal efficacy.

Differential Adaptive Responses of Staphylococcus aureus to In Vitro Selection with Different Antimicrobial Peptides

Abstract: We subjected Staphylococcus aureus ATCC 29213 to serial passage in the presence of subinhibitory concentrations of magainin 2 and gramicidin D for several hundred generations. We obtained S. aureus strains with induced resistance to magainin 2 (strain 55MG) and gramicidin D (strain 55GR) that showed different phenotypic changes in membrane properties. Both exhibited a change in membrane phospholipid content and an increase in membrane rigidity, while an alteration in net charge compared to that of the control occurred only in the case of 55MG.

Resolution of inflammation: a new therapeutic frontier.

Abstract: Dysregulated inflammation is a central pathological process in diverse disease states. Traditionally, therapeutic approaches have sought to modulate the pro- or anti-inflammatory limbs of inflammation, with mixed success. However, insight into the pathways by which inflammation is resolved has highlighted novel opportunities to pharmacologically manipulate these processes - a strategy that might represent a complementary (and perhaps even superior) therapeutic approach. This Review discusses the state of the art in the biology of resolution of inflammation, highlighting the opportunities and challenges for translational research in this field.

Bactericidal activity of curcumin I is associated with damaging of bacterial membrane.

Abstract: 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.

Antibiotic development challenges: the various mechanisms of action of antimicrobial peptides and of bacterial resistance

Abstract: Antimicrobial peptides (AMPs) are natural antibiotics produced by various organisms such as mammals, arthropods, plants, and bacteria. In addition to antimicrobial activity, AMPs can induce chemokine production, accelerate angiogenesis, and wound healing and modulate apoptosis in multicellular organisms. Originally, their antimicrobial mechanism of action was thought to consist solely of an increase in pathogen cell membrane permeability, but it has already been shown that several AMPs do not modulate membrane permeability in the minimal lethal concentration. Instead, they exert their effects by inhibiting processes such as protein and cell wall synthesis, as well as enzyme activity, among others. Although resistance to these molecules is uncommon several pathogens developed different strategies to overcome AMPs killing such as surface modification, expression of efflux pumps, and secretion of proteases among others. This review describes the various mechanisms of action of AMPs and how pathogens evolve resistance to them.

Review on plant antimicrobials: a mechanistic viewpoint

Abstract: Microbial resistance to classical antibiotics and its rapid progression have raised serious concern in the treatment of infectious diseases. Recently, many studies have been directed towards finding promising solutions to overcome these problems. Phytochemicals have exerted potential antibacterial activities against sensitive and resistant pathogens via different mechanisms of action. In this review, we have summarized the main antibiotic resistance mechanisms of bacteria and also discussed how phytochemicals belonging to different chemical classes could reverse the antibiotic resistance. Next to containing direct antimicrobial activities, some of them have exerted in vitro synergistic effects when being combined with conventional antibiotics. Considering these facts, it could be stated that phytochemicals represent a valuable source of bioactive compounds with potent antimicrobial activities.

Antimicrobial peptides and wound healing: biological and therapeutic considerations

Abstract: Repair of tissue wounds is a fundamental process to re-establish tissue integrity and regular function. Importantly, infection is a major factor that hinders wound healing. Multicellular organisms have evolved an arsenal of host-defense molecules, including antimicrobial peptides (AMPs), aimed at controlling microbial proliferation and at modulating the host's immune response to a variety of biological or physical insults. In this brief review, we provide the evidence for a role of AMPs as endogenous mediators of wound healing and their promising therapeutic potential for the treatment of non-life-threatening skin and other epithelial injuries.