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15 pages, 5659 KiB

Open AccessArticle

A New Albomycin-Producing Strain of Streptomyces globisporus subsp. globisporus May Provide Protection for Ants Messor structor

by Yuliya V. Zakalyukina, Nikolay A. Pavlov, Dmitrii A. Lukianov, Valeria I. Marina, Olga A. Belozerova, Vadim N. Tashlitsky, Elena B. Guglya, Ilya A. Osterman and Mikhail V. Biryukov

Insects 2022, 13(11), 1042; https://doi.org/10.3390/insects13111042 - 11 Nov 2022

Cited by 8 | Viewed by 2760

Abstract

There are several well-studied examples of protective symbiosis between insect host and symbiotic actinobacteria, producing antimicrobial metabolites to inhibit host pathogens. These mutualistic relationships are best described for some wasps and leaf-cutting ants, while a huge variety of insect species still remain poorly explored. For the first time, we isolated actinobacteria from the harvester ant Messor structor and evaluated the isolates’ potential as antimicrobial producers. All isolates could be divided into two morphotypes of single and mycelial cells. We found that the most common mycelial morphotype was observed among soldiers and least common among larvae in the studied laboratory colony. The representative of this morphotype was identified as Streptomyces globisporus subsp. globisporus 4-3 by a polyphasic approach. It was established using a E. coli JW5503 pDualRep2 system that crude broths of mycelial isolates inhibited protein synthesis in reporter strains, but it did not disrupt the in vitro synthesis of proteins in cell-free extracts. An active compound was extracted, purified and identified as albomycin δ2. The pronounced ability of albomycin to inhibit the growth of entomopathogens suggests that Streptomyces globisporus subsp. globisporus may be involved in defensive symbiosis with the Messor structor ant against infections. Full article

(This article belongs to the Special Issue Insect Microbiome and Immunity)

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12 pages, 2215 KiB

Open AccessReview

Biosynthesis and Chemical Synthesis of Albomycin Nucleoside Antibiotics

by Meiyan Wang, Yuxin Zhang, Lanxin Lv, Dekun Kong and Guoqing Niu

Antibiotics 2022, 11(4), 438; https://doi.org/10.3390/antibiotics11040438 - 24 Mar 2022

Cited by 13 | Viewed by 4267

Abstract

The widespread emergence of antibiotic-resistant bacteria highlights the urgent need for new antimicrobial agents. Albomycins are a group of naturally occurring sideromycins with a thionucleoside antibiotic conjugated to a ferrichrome-type siderophore. The siderophore moiety serves as a vehicle to deliver albomycins into bacterial cells via a “Trojan horse” strategy. Albomycins function as specific inhibitors of seryl-tRNA synthetases and exhibit potent antimicrobial activities against both Gram-negative and Gram-positive bacteria, including many clinical pathogens. These distinctive features make albomycins promising drug candidates for the treatment of various bacterial infections, especially those caused by multidrug-resistant pathogens. We herein summarize findings on the discovery and structure elucidation, mechanism of action, biosynthesis and immunity, and chemical synthesis of albomcyins, with special focus on recent advances in the biosynthesis and chemical synthesis over the past decade (2012–2022). A thorough understanding of the biosynthetic pathway provides the basis for pathway engineering and combinatorial biosynthesis to create new albomycin analogues. Chemical synthesis of natural congeners and their synthetic analogues will be useful for systematic structure–activity relationship (SAR) studies, and thereby assist the design of novel albomycin-derived antimicrobial agents. Full article

(This article belongs to the Special Issue Challenges and Opportunities in Antibiotic Biosynthesis and Development)

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34 pages, 9519 KiB

Open AccessReview

Aminoacyl-tRNA Synthetases as Valuable Targets for Antimicrobial Drug Discovery

by Luping Pang, Stephen D. Weeks and Arthur Van Aerschot

Int. J. Mol. Sci. 2021, 22(4), 1750; https://doi.org/10.3390/ijms22041750 - 10 Feb 2021

Cited by 58 | Viewed by 13689

Abstract

Aminoacyl-tRNA synthetases (aaRSs) catalyze the esterification of tRNA with a cognate amino acid and are essential enzymes in all three kingdoms of life. Due to their important role in the translation of the genetic code, aaRSs have been recognized as suitable targets for the development of small molecule anti-infectives. In this review, following a concise discussion of aaRS catalytic and proof-reading activities, the various inhibitory mechanisms of reported natural and synthetic aaRS inhibitors are discussed. Using the expanding repository of ligand-bound X-ray crystal structures, we classified these compounds based on their binding sites, focusing on their ability to compete with the association of one, or more of the canonical aaRS substrates. In parallel, we examined the determinants of species-selectivity and discuss potential resistance mechanisms of some of the inhibitor classes. Combined, this structural perspective highlights the opportunities for further exploration of the aaRS enzyme family as antimicrobial targets. Full article

(This article belongs to the Special Issue Enzymes as Targets for Drug Development II)

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