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1.
J Microbiol ; 59(12): 1083-1091, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34865197

RESUMO

CatR, a peroxide-sensing transcriptional repressor of Fur family, can de-repress the transcription of the catA gene encoding catalase upon peroxide stress in Streptomyces coelicolor. Since CatR-regulated genes other than catA and its own gene catR have not been identified in detail, the understanding of the role of CatR regulon is very limited. In this study, we performed transcriptomic analysis to identify genes influenced by both ΔcatR mutation and hydrogen peroxide treatment. Through ChIP-qPCR and other analyses, a new consensus sequence was found in CatR-responsive promoter region of catR gene and catA operon for direct regulation. In addition, vtlA (SCO2027) and SCO4983 were identified as new members of the CatR regulon. Expression levels of iron uptake genes were reduced by hydrogen peroxide and a DmdR1 binding sequence was identified in promoters of these genes. The increase in free iron by hydrogen peroxide was thought to suppress the iron import system by DmdR1. A putative exporter protein VtlA regulated by CatR appeared to reduce intracellular iron to prevent oxidative stress. The name vtlA (VIT1-like transporter) was proposed for iron homeostasis related gene SCO2027.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Ligação a DNA/metabolismo , Peróxido de Hidrogênio/farmacologia , Ferro/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Streptomyces coelicolor/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Bactérias/genética , Catalase/genética , Catalase/metabolismo , Proteínas de Ligação a DNA/genética , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Genes Bacterianos , Homeostase , Peróxido de Hidrogênio/metabolismo , Óperon , Estresse Oxidativo , Regiões Promotoras Genéticas , Regulon , Streptomyces coelicolor/genética , Fatores de Transcrição/genética , Transcrição Gênica
2.
mBio ; 11(2)2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32291305

RESUMO

Bacteria that encounter antibiotics can efficiently change their physiology to develop resistance. This intrinsic antibiotic resistance is mediated by multiple pathways, including a regulatory system(s) that activates specific genes. In some Streptomyces and Mycobacterium spp., the WblC/WhiB7 transcription factor is required for intrinsic resistance to translation-targeting antibiotics. Wide conservation of WblC/WhiB7 within Actinobacteria indicates a critical role of WblC/WhiB7 in developing resistance to such antibiotics. Here, we identified 312 WblC target genes in Streptomyces coelicolor, a model antibiotic-producing bacterium, using a combined analysis of RNA sequencing and chromatin immunoprecipitation sequencing. Interestingly, WblC controls many genes involved in translation, in addition to previously identified antibiotic resistance genes. Moreover, WblC promotes translation rate during antibiotic stress by altering the ribosome-associated protein composition. Our genome-wide analyses highlight a previously unappreciated antibiotic resistance mechanism that modifies ribosome composition and maintains the translation rate in the presence of sub-MIC levels of antibiotics.IMPORTANCE The emergence of antibiotic-resistant bacteria is one of the top threats in human health. Therefore, we need to understand how bacteria acquire resistance to antibiotics and continue growth even in the presence of antibiotics. Streptomyces coelicolor, an antibiotic-producing soil bacterium, intrinsically develops resistance to translation-targeting antibiotics. Intrinsic resistance is controlled by the WblC/WhiB7 transcription factor that is highly conserved within Actinobacteria, including Mycobacterium tuberculosis Here, identification of the WblC/WhiB7 regulon revealed that WblC/WhiB7 controls ribosome maintenance genes and promotes translation in the presence of antibiotics by altering the composition of ribosome-associated proteins. Also, the WblC-mediated ribosomal alteration is indeed required for resistance to translation-targeting antibiotics. This suggests that inactivation of the WblC/WhiB7 regulon could be a potential target to treat antibiotic-resistant mycobacteria.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Biossíntese de Proteínas/efeitos dos fármacos , Ribossomos/genética , Streptomyces coelicolor/efeitos dos fármacos , Streptomyces coelicolor/genética , Fatores de Transcrição/genética , Farmacorresistência Bacteriana Múltipla , Regulação Bacteriana da Expressão Gênica , Testes de Sensibilidade Microbiana , Regulon , Ribossomos/química
3.
J Microbiol Biotechnol ; 25(10): 1599-605, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26032364

RESUMO

The development of rapid and efficient genome sequencing methods has enabled us to study the evolutionary background of bacterial genetic information. Here, we present comparative genomic analysis of 17 Streptomyces species, for which the genome has been completely sequenced, using the pan-genome approach. The analysis revealed that 34,592 ortholog clusters constituted the pan-genome of these Streptomyces species, including 2,018 in the core genome, 11,743 in the dispensable genome, and 20,831 in the unique genome. The core genome was converged to a smaller number of genes than reported previously, with 3,096 gene families. Functional enrichment analysis showed that genes involved in transcription were most abundant in the Streptomyces pan-genome. Finally, we investigated core genes for the sigma factors, mycothiol biosynthesis pathway, and secondary metabolism pathways; our data showed that many genes involved in stress response and morphological differentiation were commonly expressed in Streptomyces species. Elucidation of the core genome offers a basis for understanding the functional evolution of Streptomyces species and provides insights into target selection for the construction of industrial strains.


Assuntos
Variação Genética , Genoma Bacteriano , Streptomyces/classificação , Streptomyces/genética , Biologia Computacional , Genes Bacterianos , Genômica
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