Antimicrobial and antibiofilm potential of α-MSH derived cationic and hydrophobic peptides against Escherichia coli: Mechanistic insight through peptide-lipopolysaccharide interactions.

The prevalence of infections caused by various Gram-negative pathogens specifically Escherichia coli continuously poses a significant challenge in health care as well as community settings owing to their ability to form biofilm and escalating tolerance towards available antibiotics. While most treatment regimes are targeted at eliminating the E. coli cells, the pathogenicity factors called endotoxin (lipopolysaccharides), associated with the sepsis initiation and the leading cause of death in intensive care units globally, are often ignored.

Prevalence and molecular characterization of multidrug-resistant coagulase negative staphylococci from urban wastewater in Delhi-NCR, India.

Antimicrobial resistance (AMR) is global health concern escalating rapidly in both clinical settings and environment. The effluent from pharmaceuticals and hospitals may contain diverse antibiotics, exerting selective pressure to develop AMR. To study the aquatic prevalence of drug-resistant staphylococci, sampling was done from river Yamuna (3 sites) and wastewater (7 sites) near pharmaceutical industries in Delhi-NCR, India.

A Review on Colistin Resistance: An Antibiotic of Last Resort.

Antibiotic resistance has emerged as a significant global public health issue, driven by the rapid adaptation of microorganisms to commonly prescribed antibiotics. Colistin, previously regarded as a last-resort antibiotic for treating infections caused by Gram-negative bacteria, is increasingly becoming resistant due to chromosomal mutations and the acquisition of resistance genes carried by plasmids, particularly the genes. The mobile colistin resistance gene (-1) was first discovered in from China in 2016.

Interaction with lipopolysaccharide is key to efficacy of tryptophan- and arginine-rich α-melanocyte-stimulating hormone analogs against Gram-negative bacteria.

In order to search for novel antibacterial therapeutics against Gram-negative bacteria, the antibacterial efficacies and mechanism of action of tryptophan- and arginine-rich α-melanocyte-stimulating hormone analogs were investigated. We performed a killing assay to determine their efficacy; fluorescence, microscopic studies were used to understand their mechanism and peptide-lipopolysaccharide interaction. A checkerboard assay was used to find the effective combination of peptide and antibiotics.

Synergistic Potential of α-Melanocyte Stimulating Hormone Based Analogues with Conventional Antibiotic against Planktonic, Biofilm-Embedded, and Systemic Infection Model of MRSA.

The repotentiation of the existing antibiotics by exploiting the combinatorial potential of antimicrobial peptides (AMPs) with them is a promising approach to address the challenges of slow antibiotic development and rising antimicrobial resistance. In the current study, we explored the ability of lead second generation Ana-peptides viz. Ana-9 and Ana-10, derived from Alpha-Melanocyte Stimulating Hormone (α-MSH), to act synergistically with different classes of conventional antibiotics against methicillin-resistant (MRSA).

Efficacy and Toxicity Studies of Novel α-MSH Analogues with Antibiofilm Action and β-Lactam Resensitization Potential against MRSA.

Methicillin-resistant (MRSA), a biofilm-forming recalcitrant pathogen with a multidrug-resistant profile, poses a pandemic threat to human health and is the leading cause of severe infections in both healthcare and community settings. In this study, toward designing novel α-MSH-based peptides with enhanced activity and stability against MRSA, particularly its stationary phase and biofilm, we explored a design approach to augment the hydrophobicity of an 8-mer C-terminal α-MSH(6-13)-based peptide Ana-5 through the incorporation of a bulky unnatural amino acid. The designed Ana-peptides overcame the limitation of diminished activity in biological media and exhibited enhanced antistaphylococcal activity and cell selectivity.

Mitigating the toxicity of palmitoylated analogue of α-melanocyte stimulating hormone(11-13) by conjugation with gold nanoparticle: characterisation and antibacterial efficacy against methicillin sensitive and resistant Staphylococccus aureus.

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.

Binding of cationic analogues of α-MSH to lipopolysaccharide and disruption of the cytoplasmic membranes caused bactericidal action against Escherichia coli.

In earlier reports, we have shown the antimicrobial activity of a host neuropeptide, alpha-melanocyte stimulating hormone (α-MSH) and its cationic analogues against Staphylococcus aureus. These analogues of α-MSH showed enhanced staphylocidal activity without any significant mammalian cell toxicity. Therefore, here, we explored the antimicrobial activity of α-MSH and its cationic analogues against Escherichia coli.

Enhanced efficacy of a Cu complex of curcumin against Gram-positive and Gram-negative bacteria: Attributes of complex formation.

Curcumin is a tantalizing molecule with multifaceted therapeutic potentials. However, its therapeutic applications are severely hampered because of poor bioavailability, attributed to its instability and aqueous insolubility. In an attempt to overcome this inherent limitation and develop curcumin-based antibacterials, we had earlier synthesized and characterized a metal complex of Cu(II) with curcumin, having the formula [Cu(Curcumin)(OCOCH)(HO)], hereafter referred to as Cu(Cur).

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

Stationary phase , especially methicillin-resistant (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 but little is known about its antimicrobial efficacy against the stationary phase of the bacteria. We investigated the activities of two palmitoylated analogues, Pal-α-MSH(6-13) and Pal-α-MSH(11-13), of the C-terminal fragments of α-MSH against biofilm-producing strains of methicillin-sensitive (MSSA) and MRSA.

Biosynthesis of Silver Nanoparticles Using Culture Supernatant of sp. ARY1 and Their Antibacterial Activity.

Purpose: In this study, silver nanoparticles (AgNPs) were biosynthesized using culture supernatant of strain sp. ARY1, characterized and their antibacterial activity was investigated against Gram-negative bacteria and

Methods: The strain sp. ARY1 was isolated from river Yamuna, Delhi and used for biosynthesis of AgNPs via extracellular approach.

Multitargeting Antibacterial Activity of a Synthesized Mn Complex of Curcumin on Gram-Positive and Gram-Negative Bacterial Strains.

Curcumin is an important molecule with a plethora of pharmacological activities and therapeutic potentials. Despite its efficacy, it remained a potential drug candidate owing to hydrolytic instability and poor aqueous solubility. To overcome the limitations related to low solubility, low bioavailability, and the fact that curcumin is never present in solution as a "single unit", its complex was prepared with Mn with the idea that binding to a metal ion might help to resolve these issues.

Prevalence and antibiogram of coagulase negative Staphylococci in bioaerosols from different indoors of a university in India.

Background: Staphylococci species are the major constituents of infectious bioaerosols, particularly methicillin-resistant Staphylococci (MRS) have serious health impacts. Here, the bacterial burden was quantified, especially prevalence of MRS in bioaerosols collected from indoors of Dr. B.

A Zn complex of ornidazole with decreased nitro radical anions that is still highly active on .

A monomeric complex of Zn with ornidazole [Zn(Onz)Cl] decreases formation of the nitro-radical anion (R-NO˙), and this is realized by recording it in an enzyme assay using xanthine oxidase, which is a model nitro-reductase. Although the formation of R-NO˙ is essential for drug action, as it is also associated with neurotoxic side effects, it is imperative to control its generation in order to avoid excess presence. With a decrease in R-NO˙, while the neurotoxic side effects should decrease, it can be expected that a compromise with regard to therapeutic efficacy will be seen since the complex will be less active in the free radical pathway.

Synthesis of novel monocarbonyl curcuminoids, evaluation of their efficacy against MRSA, including ex vivo infection model and their mechanistic studies.

In continuation of our effort to improve the physiological stability and the antibacterial activity of curcuminoids against drug-resistant bacteria, a series of novel monocarbonyl curcuminoids were synthesized and screened for antibacterial activity against S. aureus and E. coli strains.

In Vitro and Ex Vivo Efficacy of Novel Trp-Arg Rich Analogue of α-MSH against .

Antimicrobial peptides (AMPs), an essential component of innate immunity, are very important resources for human therapeutics to counter the current threat of drug resistance. We have previously established that one such AMP, α-melanocyte stimulating hormone (α-MSH), an endogenous neuropeptide, and its derivatives have potent antimicrobial activity against , including methicillin-resistant (MRSA). However, the immense potential of α-MSH for therapeutic development against staphylococcal infections is marred by its reduced efficacy in the presence of standard microbiological culture medium.

Fungal-derived xenobiotic exhibits antibacterial and antibiofilm activity against Staphylococcus aureus.

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.

Novel Miniature Membrane Active Lipopeptidomimetics against Planktonic and Biofilm Embedded Methicillin-Resistant Staphylococcus aureus.

Escalating multidrug resistance and highly evolved virulence mechanisms have aggravated the clinical menace of methicillin-resistant Staphylococcus aureus (MRSA) infections. Towards development of economically viable staphylocidal agents here we report eight structurally novel tryptophan-arginine template based peptidomimetics. Out of the designed molecules, three lipopeptidomimetics (S-6, S-7 and S-8) containing 12-amino dodecanoic acid exhibited cell selectivity and good to potent activity against clinically relevant pathogens MRSA, methicillin-resistant Staphylococcus epidermidis and vancomycin-resistant Enterococcus faecium (MIC: 1.

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

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.

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

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.

A study on the formation of the nitro radical anion by ornidazole and its significant decrease in a structurally characterized binuclear Cu(II)-complex: impact in biology.

An acetate-bridged binuclear Cu((II)) complex of the antiparasitic drug ornidazole was synthesized and characterized by different techniques. Single crystal X-ray diffraction revealed that the complex had a paddle wheel structure. Enzymatic assay experiments performed under anaerobic conditions on ornidazole and its Cu((II))-complex using xanthine oxidase as a model nitro-reductase showed that complex formation is able to cause a significant decrease in the reduction of the nitro group on the imidazole ring.

Lipid composition is an important determinant of antimicrobial activity of alpha-melanocyte stimulating hormone.

We have reported strong antimicrobial activity of cationic neuropeptide α-MSH against Staphylococcus aureus. Clinical S. aureus isolates non-susceptible to the peptide had higher amount of cationic phospholipid.

Alpha-melanocyte stimulating hormone: an emerging anti-inflammatory antimicrobial peptide.

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.

Genetic endowment of proinflammatory cytokine tumor necrosis factor-α (-) 308 G > A polymorphism to Parthenium hysterophorus-induced airborne contact dermatitis in an Indian cohort.

Background: Parthenium dermatitis is a common airborne allergic health problem that induces a cell-mediated hypersensitivity immune response involving activated T lymphocytes, which culminates in injury to the skin. The disease is manifested as itchy erythematous papules and plaques and primarily affects the exposed areas and flexures. This study aimed to identify the role of tumor necrosis factor (TNF)-α (-) 308 G>A polymorphism in the pathogenesis of parthenium dermatitis.