Saheli Mitra’s Post

#Serrawettin #W2_FL10 (derived from #Serratia_marcescens), has potential antibiotic activity against #Staphylococcus_aureus. NOTES: - W2-FL10 exhibited potent activity against the Gram-positive bacteria S. aureus, #Enterococcus_faecalis, #Enterococcus_faecium, #Listeria_monocytogenes, and #Bacillus_subtilis, with minimum inhibitory concentration (MIC) values ranging from 6.3 to 31.3 μg/mL - No activity was observed against #Gram_negative bacteria. - W2-FL10 interacted with key cell membrane components, such as lipid phosphatidyl glycerol and #lipoteichoic_acid of S. aureus. - Upon membrane interaction, W2-FL10 dissipated membrane potential within 12 min and increased S. aureus membrane permeability within 28–40 min, albeit at slower rates and higher concentrations than the lytic peptide #melittin.

🎉 Excited to share our latest research publication! 🎉 Our study explores the innovative use of salicylaldehyde derivatives and coumarin with a formyl group at the C8 position in the three-component Passerini reaction. We discovered that the reaction conditions significantly impact the products, leading to either α-hydroxy amides or α-acyloxy amides with high efficiency. Key findings: - Synthesized peptidomimetics show strong antimicrobial activity against a range of nosocomial pathogens, outperforming common antibiotics. - The presence of CF3 or methyl groups in the coumarin scaffold enhances inhibitory activity. - Cytotoxicity tests reveal these compounds are less harmful to mammalian cells than standard antibiotics. Our research opens new avenues for developing effective and safe antimicrobial agents, crucial for combating hospital-acquired infections. Check out the full publication. #Research #Antimicrobial #Peptidomimetics #Chemistry #Healthcare #Innovation ---

Experts at King's College London have made an exciting breakthrough in cyclic peptides that could open the door for developing new antibiotics to combat antimicrobial resistance (AMR). Scientists have developed a new method for rapidly making cyclic peptides – an essential type of antibiotic molecule. The innovative process takes just minutes instead of hours and even days, which it traditionally takes, significantly speeding up antibiotic development. #AMR #InfectionControl #CyclicPeptides #AntimicrobialResistance #Antibiotics https://bit.ly/3yWDaDB

#Mechanisms of Antibiotics 🦠🧫 1. Inhibition of cell wall synthesis: Certain antibiotics, such as penicillins, cephalosporins, and vancomycin, interfere with the synthesis of bacterial cell walls. They target enzymes involved in cell wall synthesis, leading to weakened cell walls, cell lysis, and bacterial death. 2. Inhibition of protein synthesis: Antibiotics like macrolides, tetracyclines, and aminoglycosides target bacterial ribosomes, the cellular structures responsible for protein synthesis. By binding to ribosomal subunits or interfering with protein elongation, these antibiotics prevent bacteria from producing essential proteins, ultimately leading to bacterial death. 3. Inhibition of nucleic acid synthesis: Some antibiotics, including quinolones and fluoroquinolones, inhibit the synthesis of bacterial DNA or RNA. By interfering with enzymes involved in DNA replication, transcription, or repair, these antibiotics disrupt bacterial nucleic acid synthesis and inhibit bacterial growth. 4. Disruption of

An exciting development...antibiotics with dual modes of action... Macrolones target bacterial ribosomes and DNA gyrase and can evade resistance mechanisms. Abstract Growing resistance toward ribosome-targeting macrolide antibiotics has limited their clinical utility and urged the search for superior compounds. Macrolones are synthetic macrolide derivatives with a quinolone side chain, structurally similar to DNA topoisomerase-targeting fluoroquinolones. While macrolones show enhanced activity, their modes of action have remained unknown. Here, we present the first structures of ribosome-bound macrolones, showing that the macrolide part occupies the macrolide-binding site in the ribosomal exit tunnel, whereas the quinolone moiety establishes new interactions with the tunnel. Macrolones efficiently inhibit both the ribosome and DNA topoisomerase in vitro. However, in the cell, they target either the ribosome or DNA gyrase or concurrently both of them. In contrast to macrolide or fluoroquinolone antibiotics alone, dual-targeting macrolones are less prone to select resistant bacteria carrying target-site mutations or to activate inducible macrolide resistance genes. Furthermore, because some macrolones engage Erm-modified ribosomes, they retain activity even against strains with constitutive erm resistance genes. https://lnkd.in/ebS_3bsw

🎯 #callforreading A new publication is now available on Targets MDPI! 🤩 Title: "SK-03-92 Treatment Causes Release of a Lethal Factor Protein That Kills Staphylococcus aureus Cells" 🔗 Link: https://lnkd.in/dwsrtU6Q 🤼 Authors: William R. Schwan, Madison Moore, Allison Zank, Sophia Cannarella, Kyle Gebhardt and John F. May University of Wisconsin-La Crosse #drugdiscovery #Streptococcus #bacterial #antibacterialdrug #SK0392treatment 📜 Abstract: Staphylococcus aureus is a leading cause of skin and bloodstream infections in humans. Antibiotic resistant strains of S. aureus continue to be a problem in treating patients that are infected, so treatment options are needed. A drug discovery project identified SK-03-92 as a novel anti-staphylococcal drug, but the SK-03-92 mechanism of action is unknown. We hypothesized that a lethal factor was being released by the bacteria that killed siblings. Methods: In this study, filtration through molecular weight cut-off filters as well as boiling, trypsin treatment, and proteinase K treatment were used to ascertain what the lethal factor was released by SK-03-92 treated S. aureus cells. Results: Filtration through molecular weight cut-off filters demonstrated the lethal factor released by SK-03-92 treated S. aureus cells had a molecular cut-off between 10,000 Da and 30,000 Da that killed fresh S. aureus cells but was not released by untreated cells. Through proteinase K digestion, trypsin digestion, and boiling experiments, the lethal factor was shown to be a protein. Further experiments are needed to identify what proteins released following SK-03-92 treatment cause the death of S. aureus cells. Conclusions: The data show that SK-03-92 treatment causes S. aureus to release a lethal factor protein that kills S. aureus cells, suggesting a new mechanism of action for an antibacterial drug.

🚀Mining human microbiomes reveals an untapped source of peptide antibiotics Drug-resistant bacteria are advancing faster than traditional antibiotic discovery can keep up. In a recent study, 444,054 previously reported putative small protein families from 1,773 human metagenomes were computationally screened for antimicrobial properties, leading to the identification of 323 candidates encoded in small open reading frames (smORFs). To validate these computational predictions, 78 peptides were synthesized and screened for antimicrobial activity in vitro, with an impressive 70.5% showing antimicrobial effects. These newly identified compounds, termed smORF-encoded peptides (SEPs), stand out from previously known antimicrobial peptides by targeting bacterial membranes, synergizing with each other, and even modulating gut commensals—suggesting a dual role in both reconfiguring microbiome communities and combating pathogens. The most promising candidates demonstrated anti-infective properties in both murine skin abscess and deep thigh infection models. Particularly noteworthy is prevotellin-2 from Prevotella copri, which exhibited activity on par with the widely used antibiotic polymyxin B. This discovery underscores the vast potential of hundreds of antimicrobial agents within the human microbiome, paving the way for future clinical applications. https://lnkd.in/g_ys7thv #microbiome #antibiotics

Daptomycin (DAP), a cyclic lipopeptide antibiotic, is crucial for addressing multidrug-resistant Staphylococcus aureus, such as MRSA. However, resistance to DAP is increasingly observed, driven by various mechanisms. Combining phages with antibiotics offers promise due to their low side effects and potential synergy. This research examined the link between DAP resistance and sensitivity to phage Sb-1 in 14 MRSA strains, including isogenic and serially passaged pairs with DAP. As DAP resistance developed, the efficiency of plating (EOP) and plaque sizes grew markedly. Phage-antibiotic combinations demonstrated less antagonism in DAP-resistant mutants than susceptible strains, with 71.4% antagonism in susceptible strains, but only 14.3% in resistant ones. Electron microscopy showed thicker cell walls in DAP-susceptible strains treated with DAP alone. These results suggest increased sensitivity to phage Sb-1 with DAP resistance. #AntibioticResistance #PhageTherapy

🌟 Unveiling Bakuchiol: A Game Changer in the Fight Against Antimicrobial Resistance! 🌟 In a world grappling with the growing threat of antimicrobial resistance, researchers are turning to innovative solutions. A recent study highlights bakuchiol, a compound from Psoralea corylifolia, showcasing its remarkable antimicrobial properties against multi-drug resistant strains of Staphylococcus aureus. 🔍 Key Findings: - Bakuchiol exhibits strong bactericidal activity with a minimum inhibitory concentration (MIC) of just 2 µg/mL! - It inhibits critical bacterial processes, offering a novel approach to combat infections where traditional antibiotics fall short. - With low toxicity and high selectivity, bakuchiol is poised for safe therapeutic use in clinical settings. This breakthrough could revolutionize our approach to treating resistant infections and pave the way for new therapeutic options. 💡 Let's advocate for the development and integration of bakuchiol into treatment regimens! 👉 Click on the embedded link to learn more about this promising research! #AntimicrobialResistance #Bakuchiol #HealthTechnologyAssessment #HealthcareResearch #PharmaceuticalInnovation #Publications #StaphylococcusAureus #MarketAccess #MarketAccessToday

Previous studies identified lysine- and tryptophan-rich sequences within various cationic antimicrobial peptides. https://lnkd.in/gzwAs5jh