834 research outputs found
Antibiotics: the molecular marvels of modern medicine
Inaugural speech delivered by Prof.dr. Nathaniel I. Martin at the acceptance of professor Biological Chemistry at the Faculty of Sciences at Leiden University on September 13. 2019.Microbial Biotechnolog
Synergy by perturbing the gram-negative outer membrane: opening the door for gram-positive specific antibiotics
New approaches to target antibacterial agents toward Gram -negative bacteria are key, given the rise of antibiotic resistance. Since the discovery of polymyxin B nonapeptide as a potent Gram-negative outer membrane (OM)-permeabilizing synergist in the early 1980s, a vast amount of literature on such synergists has been published. This Review addresses a range of peptide-based and small organic compounds that disrupt the OM to elicit a synergistic effect with antibiotics that are otherwise inactive toward Gram -negative bacteria, with synergy defined as a fractional inhibitory concentration index (FICI) of <0.5. Another requirement for the inclusion of the synergists here covered is their potentiation of a specific set of clinically used antibiotics: erythromycin, rifampicin, novobiocin, or vancomycin. In addition, we have focused on those synergists with reported activity against Gram-negative members of the ESKAPE family of pathogens namely, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and/or Acinetobacter baumannii. In cases where the FICI values were not directly reported in the primary literature but could be calculated from the published data, we have done so, allowing for more direct comparison of potency with other synergists. We also address the hemolytic activity of the various OM-disrupting synergists reported in the literature, an effect that is often downplayed but is of key importance in assessing the selectivity of such compounds for Gram-negative bacteria.Microbial Biotechnolog
Thiol-Containing Metallo-Ξ²-Lactamase Inhibitors Resensitize Resistant Gram-Negative Bacteria to Meropenem
Microbial Biotechnolog
A convenient chemoenzymatic preparation of chimeric macrocyclic peptide antibiotics with potent activity against gram-negative pathogens
Microbial Biotechnolog
The contribution of achiral residues in the laspartomycin family of calcium-dependent lipopeptide antibiotics
The growing threat of antibacterial resistance is a global concern. The so-called calcium-dependent lipopeptide antibiotics (CDAs) have emerged as a promising source of new antibiotic agents that are rich in structural and mechanistic diversity. Over forty unique CDAs have been identified to date and share a number of common features. Recent efforts in our group have provided new mechanistic and structural insights into the laspartomycin family of CDAs. We here describe investigations aimed at probing the role of the three glycine residues found in the laspartomycin peptide macrocycle. In doing so laspartomycin analogues containing the achiral 2-aminoisobutyric acid (AIB) as well as L- or D-alanine in place of glycine were prepared and their antibacterial activities evaluated.Microbial Biotechnolog
Nicotinamide N-Methyl Transferase (NNMT): an emerging therapeutic target
Microbial Biotechnolog
Recent advances in the development of semisynthetic glycopeptide antibiotics: 2014β2022
The accelerated appearance of drug-resistant bacteria poses an ever-growing threat to modern medicine's capacity to fight infectious diseases. Gram-positive species such as methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae continue to contribute significantly to the global burden of antimicrobial resistance. For decades, the treatment of serious Gram-positive infections relied upon the glycopeptide family of antibiotics, typified by vancomycin, as a last line of defense. With the emergence of vancomycin resistance, the semisynthetic glycopeptides telavancin, dalbavancin, and oritavancin were developed. The clinical use of these compounds is somewhat limited due to toxicity concerns and their unusual pharmacokinetics, highlighting the importance of developing next-generation semisynthetic glycopeptides with enhanced antibacterial activities and improved safety profiles. This Review provides an updated overview of recent advancements made in the development of novel semisynthetic glycopeptides, spanning the period from 2014 to today. A wide range of approaches are covered, encompassing innovative strategies that have delivered semisynthetic glycopeptides with potent activities against Gram-positive bacteria, including drug-resistant strains. We also address recent efforts aimed at developing targeted therapies and advances made in extending the activity of the glycopeptides toward Gram-negative organisms.Microbial Biotechnolog
Polymyxin stereochemistry and its role in antibacterial activity and outer membrane disruption
Microbial Biotechnolog
ΠΠ°ΡΡΠΎΠ½Π°Π»ΡΠ½Ρ ΡΠ΅Π½Π΄Π΅Π½ΡΡΡ ΡΠΎΠ·Π²ΠΈΡΠΊΡ ΡΠ½ΡΠ²Π΅ΡΡΠΈΡΠ΅ΡΡΡΠΊΠΎΡ ΠΎΡΠ²ΡΡΠΈ
Π ΡΡΡΠ°ΡΠ½ΠΎΠΌΡ Π΄ΠΈΠ½Π°ΠΌΡΡΠ½ΠΎ Π·ΠΌΡΠ½ΡΠ²Π°Π½ΠΎΠΌΡ ΡΠ²ΡΡΡ ΡΠ½ΡΠ²Π΅ΡΡΠΈΡΠ΅Ρ - ΡΠ΅ ΠΏΠ΅ΡΡ Π·Π° Π²ΡΠ΅ Π²ΠΈΡΠΈΠΉ Π½Π°Π²ΡΠ°Π»ΡΠ½ΠΈΠΉ Π·Π°ΠΊΠ»Π°Π΄, ΡΠΊΠΈΠΉ Ρ ΡΠ½Π΄ΠΈΠΊΠ°ΡΠΎΡΠΎΠΌ ΡΠΈΠ²ΡΠ»ΡΠ·Π°ΡΡΠΉΠ½ΠΎΡΡΡ ΡΠ΅Π³ΡΠΎΠ½Ρ ΡΠ° Π΄Π΅ΡΠΆΠ°Π²ΠΈ. ΠΡΠΎΡΠ΅ Ρ Π½Π°ΡΡ Π΄Π½Ρ ΠΊΠ»Π°ΡΠΈΡΠ½Ρ ΡΠ½ΡΠ²Π΅ΡΡΠΈΡΠ΅ΡΠΈ ΠΏΠΎΡΡΠ°Π»ΠΈ ΠΏΠ΅ΡΠ΅Π΄ ΡΠ΅ΡΠΉΠΎΠ·Π½ΠΈΠΌΠΈ Π²ΠΈΠΊΠ»ΠΈΠΊΠ°ΠΌΠΈ ΡΠ°ΡΡ.Π ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΠΌ Π΄ΠΈΠ½Π°ΠΌΠΈΡΠ΅ΡΠΊΠΈ ΠΈΠ·ΠΌΠ΅Π½ΡΡΡΠ΅ΠΌΡΡ ΠΌΠΈΡΠ΅ ΡΠ½ΠΈΠ²Π΅ΡΡΠΈΡΠ΅Ρ - ΡΡΠΎ ΠΏΡΠ΅ΠΆΠ΄Π΅ Π²ΡΠ΅Π³ΠΎ Π²ΡΡΡΠ΅Π΅ ΡΡΠ΅Π±Π½ΠΎΠ΅ Π·Π°Π²Π΅Π΄Π΅Π½ΠΈΠ΅, ΠΊΠΎΡΠΎΡΠΎΠ΅ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΈΠ½Π΄ΠΈΠΊΠ°ΡΠΎΡΠΎΠΌ ΡΠΈΠ²ΠΈΠ»ΠΈΠ·Π°ΡΠΈΠΎΠ½Π½ΠΎΡΡΠΈ ΡΠ΅Π³ΠΈΠΎΠ½Π° ΠΈ Π³ΠΎΡΡΠ΄Π°ΡΡΡΠ²Π°. ΠΠ΄Π½Π°ΠΊΠΎ Π² Π½Π°ΡΠΈ Π΄Π½ΠΈ ΠΊΠ»Π°ΡΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠ½ΠΈΠ²Π΅ΡΡΠΈΡΠ΅ΡΡ Π²ΡΡΠ°Π»ΠΈ ΠΏΠ΅ΡΠ΅Π΄ ΡΠ΅ΡΡΠ΅Π·Π½ΡΠΌΠΈ Π²ΡΠ·ΠΎΠ²Π°ΠΌΠΈ Π²ΡΠ΅ΠΌΠ΅Π½ΠΈ
A ban on BAM: an update on inhibitors of the Ξ²-barrel assembly machinery
Microbial Biotechnolog
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