Amin Marashi’s Post

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

#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

Exciting news in the fight against antibiotic resistance! Our team has explored antimicrobial peptides (AMPs) as an alternative to antibiotics and the results are promising. Our key findings reveal that LE-53 (12-mer) outperformed LE-55 (16-mer) against bacteria, while sparing eukaryotic cells. We also discovered that LE-53's effectiveness is due to increased hydrophobicity, and that secondary structure is not the sole factor. Our research also uncovered a significant link between LE-53's upper hydrocarbon location in G(-) and G(+) LMMs and its efficacy. Neutron Reflectometry (NR) confirmed the AMP locations determined using XDS, while Solution small-angle X-ray scattering (SAXS) demonstrated LE-53's ability to induce vesicle fusion in bacterial LMMs without affecting eukaryotic LMMs. These findings offer a promising strategy to combat antibiotic-resistant strains while preserving human cell integrity. Our research paves the way for innovative approaches in the fight against antibiotic resistance. Let's connect and discuss how AMPs can revolutionize healthcare! #AntibioticResistance #ResearchInnovation https://lnkd.in/ehfujwiA

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

LL-37 is a peptide that is derived from human cathelicidin (hCAP18). Cathelicidin peptides are a family of naturally occurring antimicrobial peptides found in the immune system of various organisms, including humans. These peptides play a crucial role in the body's defense against infections. LL-37 is a short cationic peptide chain composed of 37 amino acids that can interact with negatively charged components of microbial membranes such as lipopolysaccharides. Upon binding, LL-37 disrupts the microbial membrane integrity, leading to cell lysis and cell death. It has been extensively studied not only for its antimicrobial properties but also for its ability to modulate the immune response. To purchase, please visit our online shop: https://lnkd.in/eWUhrnEi. For any custom peptides, you can also contact our experts at info@altabioscience.com. #peptide #peptidesynthesis #antimicrobial #microbiology #lifesciences

Ciprofloxacin (CPX) is one of the most employed antibiotics in clinics to date. However, the rise of drug-resistant bacteria is dramatically impairing its efficacy, especially against life-threatening pathogens, such as Pseudomonas aeruginosa. This Gram-negative bacterium is an opportunistic pathogen, often infecting immuno-compromised patients with severe or fatal outcomes. The evidence of the possibility of exploiting Carbonic Anhydrase (CA, EC: 4.2.1.1) enzymes as pharmacological targets along with their role in P. aeruginosa virulence inspired the derivatization of CPX with peculiar CA-inhibiting chemotypes. Thus, a large library of CPX derivatives was synthesized and tested on a panel of bacterial CAs and human isoenzymes I and II. Selected derivatives were evaluated for antibacterial activity, revealing bactericidal and antibiofilm properties for some compounds. Importantly, promising preliminary absorption, distribution, metabolism, and excretion (ADME) properties in vitro were found and no cytotoxicity was detected for some representative compounds when tested in Galleria mellonella larvae.

The feature of deleting the fear of transfusion reaction is coming. Read the abstract of a paper I came across recently. Title: Akkermansia muciniphila exoglycosidases target extended blood group antigens to generate ABO-universal blood. Abstract: “Matching donor and recipient blood groups based on red blood cell (RBC) surface ABO glycans and antibodies in plasma is crucial to avoid potentially fatal reactions during transfusions. Enzymatic conversion of RBC glycans to the universal group O is an attractive solution to simplify blood logistics and prevent ABO-mismatched transfusions. The gut symbiont Akkermansia muciniphila can degrade mucin O-glycans including ABO epitopes. Here we biochemically evaluated 23 Akkermansia glycosyl hydrolases and identified exoglycosidase combinations which efficiently transformed both A and B antigens and four of their carbohydrate extensions. Enzymatic removal of canonical and extended ABO antigens on RBCs significantly improved compatibility with group O plasmas, compared to conversion of A or B antigens alone. Finally, structural analyses of two B-converting enzymes identified a previously unknown putative carbohydrate-binding module. This study demonstrates the potential utility of mucin-degrading gut bacteria as valuable sources of enzymes for production of universal blood for transfusions”. #Transfusionmedicine, #PublicHealth, #Transfusionreaction. Read:

Interesting synthetic two target antibiotic potential. It is a combination of macrolide and quinoline functional groups called macrolone. Could this synthetic antibiotic be the solution to multidrug resistant bacteria? I am skeptical of this claim. As past activities have shown, bacteria are extremely resourceful and make plenty of mutations. This will probably help in the short- to mid-term, but I have a feeling there will eventually be bacterial resistance to these. #publichealth #labmedicine #clinmicro #microbiology #multidrugresistance #mdr #antibiotics #macrolone https://lnkd.in/gKp7JG5g

Antibiotics are powerful weapons against bacterial infections, but have you ever wondered how they work? Here's a simple breakdown of their modes of action: 1. Inhibition of Cell Wall Synthesis: Some antibiotics, like penicillins and cephalosporins, disrupt the bacterial cell wall, causing it to burst. 2. Inhibition of Protein Synthesis: Antibiotics like tetracyclines and macrolides block the bacterial ribosomes, stopping them from making essential proteins. 3. Inhibition of DNA/RNA Synthesis: Quinolones and rifampin target bacterial enzymes involved in DNA or RNA replication, halting bacterial reproduction. 4. Disruption of Cell Membrane: Antibiotics like polymyxins damage the bacterial cell membrane, leading to leakage and cell death. 5. Inhibition of Metabolic Pathways: Sulfonamides and trimethoprim interfere with vital bacterial metabolic processes, such as folic acid synthesis. Understanding how antibiotics work helps us appreciate their importance and the need to use them responsibly to combat antibiotic resistance. #Antibiotics #Pharmacology #Healthcare #InfectionControl #AntimicrobialResistance #Microbiology #PharmaScience #ModeOfAction #HealthAwareness #ResponsibleUse

Antimicrobial peptides Mechanisms of action of AMPs The ability of AMPs to kill bacteria usually depends upon their ability to interact with bacterial membranes or cell walls. Generally, AMPs exhibit a net positive charge and a high ratio of hydrophobic amino acids, allowing them to selectively bind to negatively charged bacterial membranes. Binding of AMPs to the bacterial membrane leads to non-enzymatic disruption. Selectivity for specific species is due to differences in the membrane composition of different microbes and cell types. Defensins and cathelicidins comprise the major families of membrane-disrupting peptides in vertebrates. The electrostatic interaction between defensin’s cationic residue clusters and negatively charged phospholipid groups can form pores in the bacterial membrane that destroy membrane integrity, promoting lysis of the targeted microbes . Like defensins, most cathelicidins also kill bacteria by membrane disruption. The human cathelicidin peptide LL37 is cationic, α-helical and binds to membranes through electrostatic interactions, followed by peptide insertion and membrane disruption. Some AMPs also disrupt bacterial membranes through enzymatic digestion. For example, lysozyme hydrolyses the beta-glycosidic linkage between N-acetylmuramic acid and N-acetyl glucosamine in the peptidoglycan of bacterial cell walls, and phospholipase A2 (PLA2) secreted from human platelets kills bacteria by hydrolyzing bacterial membrane phospholipids. Nonetheless, some peptides have been described as being able to cross the lipid bilayer without causing any damage, but kill bacteria by inhibiting intracellular functions, such as blocking enzyme activity or inhibiting protein and nucleic acid synthesis. In addition to direct antimicrobial activities, some AMPs are also able to inhibit biofilm formation and disrupt existing biofilms.