Pharmacokinetic and pharmacodynamic evaluation of the atypical tetracyclines chelocardin and amidochelocardin in murine infection models.

There is a strong need to find novel treatment options against urinary tract infections associated with antimicrobial resistance. This study evaluates two atypical tetracyclines, namely chelocardin (CHD) and amidochelocardin (CDCHD), with respect to their pharmacokinetics and pharmacodynamics. We show CHD and CDCHD are cleared at high concentrations in mouse urine.

Amidochelocardin Overcomes Resistance Mechanisms Exerted on Tetracyclines and Natural Chelocardin.

The reassessment of known but neglected natural compounds is a vital strategy for providing novel lead structures urgently needed to overcome antimicrobial resistance. Scaffolds with resistance-breaking properties represent the most promising candidates for a successful translation into future therapeutics. Our study focuses on chelocardin, a member of the atypical tetracyclines, and its bioengineered derivative amidochelocardin, both showing broad-spectrum antibacterial activity within the ESKAPE (, and species) panel.

Semisynthesis and biological evaluation of amidochelocardin derivatives as broad-spectrum antibiotics.

To address the global challenge of emerging antimicrobial resistance, the hitherto most successful strategy to new antibiotics has been the optimization of validated natural products; most of these efforts rely on semisynthesis. Herein, we report the semisynthetic modification of amidochelocardin, an atypical tetracycline obtained via genetic engineering of the chelocardin producer strain. We report modifications at C4, C7, C10 and C11 by the application of methylation, acylation, electrophilic substitution, and oxidative C-C coupling reactions.

Engineering Atypical Tetracycline Formation in Amycolatopsis sulphurea for the Production of Modified Chelocardin Antibiotics.

To combat the increasing spread of antimicrobial resistance and the shortage of novel anti-infectives, one strategy for the development of new antibiotics is to optimize known chemical scaffolds. Here, we focus on the biosynthetic engineering of Amycolatopsis sulphurea for derivatization of the atypical tetracycline chelocardin and its potent broad-spectrum derivative 2-carboxamido-2-deacetyl-chelocardin. Heterologous biosynthetic genes were introduced into this chelocardin producer to modify functional groups and generate new derivatives.

A polyphasic approach leads to seven new species of the cellulose-decomposing genus Sorangium, Sorangium ambruticinum sp. nov., Sorangium arenae sp. nov., Sorangium bulgaricum sp. nov., Sorangium dawidii sp. nov., Sorangium kenyense sp. nov., Sorangium orientale sp. nov. and Sorangium reichenbachii sp. nov.

Seventy-three strains of Sorangium have been isolated from soil samples collected from all over the world. The strains were characterized using a polyphasic approach and phenotypic, genotypic and chemotype analyses clarified their taxonomic relationships. 16S rRNA, xynB1, groEL1, matrix-assisted laser desorption/ioniziation time-of-flight mass spectrometry and API-ZYM analyses were conducted.

Genome-wide mutant profiling predicts the mechanism of a Lipid II binding antibiotic.

Identifying targets of antibacterial compounds remains a challenging step in the development of antibiotics. We have developed a two-pronged functional genomics approach to predict mechanism of action that uses mutant fitness data from antibiotic-treated transposon libraries containing both upregulation and inactivation mutants. We treated a Staphylococcus aureus transposon library containing 690,000 unique insertions with 32 antibiotics.

Racemicystis persica sp. nov., a myxobacterium from soil.

A novel myxobacterium, strain MSr11462T, was isolated in 2015 from a soil sample collected form Kish Island beach, Persian Gulf, Iran. It displayed general myxobacterial features like Gram-negative staining, rod-shaped vegetative cells, gliding on solid surfaces, microbial lytic activity, fruiting-body-like aggregates and myxospore-like structures. The strain was mesophilic, aerobic and showed a chemoheterotrophic mode of nutrition.