A putative mechanism underlying secondary metabolite overproduction by Streptomyces strains with a 23S rRNA mutation conferring erythromycin resistance

Hoshino, Kanata; Imai, Yu; Mukai, Keiichiro; Hamauzu, Ryoko; Ochi, Kozo; Hosaka, Takeshi

doi:10.1007/s00253-019-10288-1

Cited by 10 publications

(4 citation statements)

References 45 publications

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“…This discrepancy suggests local adaptation of the cluster C species to unique selection pressures in different regions, including differences in agriculture, industry, lifestyle, and also antibiotic and other drug policy (higher consumption of SXT and macrolides in Czech Republic compared to Spain) 67 , 68 . Spontaneous mutations conferring ERY-resistance under selection pressure have already been demonstrated in the model actinomycetes S. coelicolor and S. lividans 69 and are associated with point mutations in rrnA -23S rRNA and rrnC -23S rRNA 70 . Since SXT resistance determinants are located on mobile elements such as small plasmids and gene cassettes 71 , horizontal gene transfer under appropriate conditions is a possibility, although it has not yet been documented for Streptomyces .…”

Section: Discussionmentioning

confidence: 83%

Evaluation and comparison of antibiotic susceptibility profiles of Streptomyces spp. from clinical specimens revealed common and region-dependent resistance patterns

Kotrbová

Lara-Rodriguez

Corretto

et al. 2022

Sci Rep

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Notwithstanding the fact that streptomycetes are overlooked in clinical laboratories, studies describing their occurrence in disease and potential pathogenicity are emerging. Information on their species diversity in clinical specimens, aetiology and appropriate therapeutic treatment is scarce. We identified and evaluated the antibiotic susceptibility profile of 84 Streptomyces clinical isolates from the Czech Republic. In the absence of appropriate disk diffusion (DD) breakpoints for antibiotic susceptibility testing (AST) of Streptomyces spp., we determined DD breakpoints by correlation with the broth microdilution method and by the distribution of zone diameters among isolates. Correlation accuracy was high for 9 antibiotics, leading to the establishment of the most valid DD breakpoints for Streptomyces antibiotic susceptibility evaluation so far. Clinical strains belonged to 17 different phylotypes dominated by a cluster of strains sharing the same percentage of 16S rRNA gene sequence identity with more than one species (S. albidoflavus group, S. hydrogenans, S. resistomycificus, S. griseochromogenes; 70% of isolates). AST results showed that Streptomyces exhibited intrinsic resistance to penicillin, general susceptibility to amikacin, gentamycin, vancomycin and linezolid, and high percentage of susceptibility to tetracyclines and clarithromycin. For the remaining antibiotics, AST showed inter- and intra-species variations when compared to available literature (erythromycin, trimethoprim-sulfamethoxazole), indicating a region-dependent rather than species-specific patterns.

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Section: Discussionmentioning

confidence: 83%

Evaluation and comparison of antibiotic susceptibility profiles of Streptomyces spp. from clinical specimens revealed common and region-dependent resistance patterns

Kotrbová

Lara-Rodriguez

Corretto

et al. 2022

Sci Rep

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“…The molecular basis of the increased resistance of KO-1305 and KO-1307 to erythromycin remains unknown. These strains have no mutations known to cause erythromycin resistance [ 31 , 32 ]. Likewise, we did not reveal mutation(s) common to both strains, which would underlie their resistance phenotype.…”

Section: Discussionmentioning

confidence: 99%

Properties of Multidrug-Resistant Mutants Derived from Heterologous Expression Chassis Strain Streptomyces albidoflavus J1074

et al. 2023

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Streptomyces albidoflavus J1074 is a popular platform to discover novel natural products via the expression of heterologous biosynthetic gene clusters (BGCs). There is keen interest in improving the ability of this platform to overexpress BGCs and, consequently, enable the purification of specialized metabolites. Mutations within gene rpoB for the β-subunit of RNA polymerase are known to increase rifampicin resistance and augment the metabolic capabilities of streptomycetes. Yet, the effects of rpoB mutations on J1074 remained unstudied, and we decided to address this issue. A target collection of strains that we studied carried spontaneous rpoB mutations introduced in the background of the other drug resistance mutations. The antibiotic resistance spectra, growth, and specialized metabolism of the resulting mutants were interrogated using a set of microbiological and analytical approaches. We isolated 14 different rpoB mutants showing various degrees of rifampicin resistance; one of them (S433W) was isolated for the first time in actinomycetes. The rpoB mutations had a major effect on antibiotic production by J1074, as evident from bioassays and LC-MS data. Our data support the idea that rpoB mutations are useful tools to enhance the ability of J1074 to produce specialized metabolites.

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“…Most ribosomal antibiotics target rRNA, so mutations in rRNA change the conformation of drug binding regions or directly make the key bases lose their interactions with drugs, thereby conferring high resistance to antibiotics 3 . For example, A23302T mutation of the 23S rRNA gene of Streptomyces coelicolor or A2281G mutation of the 23S rRNA gene of Actinomycetes leads to the resistance to erythromycin 52 . In addition to rRNA, mutations in ribosomal proteins cause antibiotic resistance, although these proteins may not directly bind to the drugs.…”

Section: Challenges and Advances In Ribosomal Antibiotics And Bacterial Ribosomesmentioning

confidence: 99%

Ribosome‐targeting antibacterial agents: Advances, challenges, and opportunities

Zhang

Bai

et al. 2021

Medicinal Research Reviews

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Ribosomes, which synthesize proteins, are critical organelles for the survival and growth of bacteria. About 60% of approved antibiotics discovered so far combat pathogenic bacteria by targeting ribosomes. However, several issues, such as drug resistance and toxicity, have impeded the clinical use of ribosome‐targeting antibiotics. Moreover, the complexity of the bacteria ribosome structure has retarded the discovery of new ribosome‐targeting agents that are considered as the key to the drug‐resistance and toxicity. To deal with these challenges, efforts such as medicinal chemistry optimization, combination treatment, and new drug delivery system have been developed. But not enough, the development of structural biology and new screening methods bring powerful tools, such as cryo‐electron microscopy technology, advanced computer‐aided drug design, and cell‐free in vitro transcription/translation systems, for the discovery of novel ribosome‐targeting antibiotics. Thus, in this paper, we overview the research on different aspects of bacterial ribosomes, especially focus on discussing the challenges in the discovery of ribosome‐targeting antibacterial drugs and advances made to address issues such as drug‐resistance and selectivity, which, we believe, provide perspectives for the discovery of novel antibiotics.

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A putative mechanism underlying secondary metabolite overproduction by Streptomyces strains with a 23S rRNA mutation conferring erythromycin resistance

Cited by 10 publications

References 45 publications

Evaluation and comparison of antibiotic susceptibility profiles of Streptomyces spp. from clinical specimens revealed common and region-dependent resistance patterns

Evaluation and comparison of antibiotic susceptibility profiles of Streptomyces spp. from clinical specimens revealed common and region-dependent resistance patterns

Properties of Multidrug-Resistant Mutants Derived from Heterologous Expression Chassis Strain Streptomyces albidoflavus J1074

Ribosome‐targeting antibacterial agents: Advances, challenges, and opportunities

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