Antimicrobial Activity of Ceftazidime-Avibactam, Ceftolozane-Tazobactam, Cefiderocol, and Novel Darobactin Analogs against Multidrug-Resistant Pseudomonas aeruginosa Isolates from Pediatric and Adolescent Cystic Fibrosis Patients.

The emergence and spread of antimicrobial resistance (AMR) in Gram-negative pathogens, such as carbapenem-resistant Pseudomonas aeruginosa, pose an increasing threat to health care. Patients with immunodeficiencies or chronic pulmonary disease, like cystic fibrosis (CF), are particularly vulnerable to Pseudomonas infections and depend heavily on antibiotic therapy. To broaden limited treatment options, this study evaluated the potency of the recently licensed drugs ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), and cefiderocol (FDC) as well as two novel preclinical antibiotics, darobactins B (DAR B) and B9 (DAR B9), against clinical P.

Production of Antimicrobial Compounds by Homologous and Heterologous Expression.

Natural product discovery campaigns aim to identify compounds with the desired bioactivity, for example, metabolites with antibiotic activity. The major driver of many projects is still the finding of bioactive extracts, which will be followed up to isolate the activity-causing agent as pure compound. However, nowadays also additional strategies can be used to increase the probability of success.

Genome-Mining-Guided Discovery and Characterization of the PKS-NRPS-Hybrid Polyoxyperuin Produced by a Marine-Derived Streptomycete.

The azinothricin family comprises several cyclic hexadepsipeptides with diverse pharmacological bioactivities, including antimicrobial, antitumoral, and apoptosis induction. In this work, using a genome mining approach, a biosynthetic gene cluster encoding an azinothricin-like compound was identified from the sp. s120 genome sequence ( BGC).

Optimization of heterologous Darobactin A expression and identification of the minimal biosynthetic gene cluster.

Darobactin A (DAR) is a ribosomally synthesized and post-translationally modified peptide (RiPP) antibiotic, which was initially identified from bacteria belonging to the genus Photorhabdus. In addition, the corresponding biosynthetic gene cluster (BGC) was identified and subsequently detected in several bacteria genera. DAR represents a highly promising lead structure for the development of novel antibacterial therapeutic agents.

characterization of 3-chloro-4-hydroxybenzoic acid building block formation in ambigol biosynthesis.

The cyanobacterium Fischerella ambigua is a natural producer of polychlorinated aromatic compounds, the ambigols A-E. The biosynthetic gene cluster (BGC) of these highly halogenated triphenyls has been recently identified by heterologous expression. It consists of 10 genes named ab1-10.