Stress‐activated expression of a Streptomyces pristinaespiralis multidrug resistance gene (ptr) in various Streptomyces spp. and Escherichia coli

Salah-Bey, Khadidja; Blanc, Véronique; Thompson, Charles J.

doi:10.1111/j.1365-2958.1995.mmi_17051001.x

Cited by 32 publications

(24 citation statements)

References 43 publications

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“…This growth arrest precedes antibiotic production (28) and can activate antibiotic biosynthetic genes (31,43), antibiotic resistance genes (50), and stress response stimulons (48), as well as arrest of ribosomal protein synthesis (3). In this work, we demonstrate that this growth arrest corresponds to the transition phase from the first vegetative compartmentalized mycelium to the second multinucleated differentiated mycelium, which is the one which produces antibiotics.…”

Section: Discussionmentioning

confidence: 90%

Mycelium Differentiation and Antibiotic Production in Submerged Cultures ofStreptomyces coelicolor

Manteca

Álvarez

Salazar

et al. 2008

Appl Environ Microbiol

142

162

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Despite the fact that most industrial processes for secondary metabolite production are performed with submerged cultures, a reliable developmental model for Streptomyces under these culture conditions is lacking. With the exception of a few species which sporulate under these conditions, it is assumed that no morphological differentiation processes take place. In this work, we describe new developmental features of Streptomyces coelicolor A3(2) grown in liquid cultures and integrate them into a developmental model analogous to the one previously described for surface cultures. Spores germinate as a compartmentalized mycelium (first mycelium). These young compartmentalized hyphae start to form pellets which grow in a radial pattern. Death processes take place in the center of the pellets, followed by growth arrest. A new multinucleated mycelium with sporadic septa (second mycelium) develops inside the pellets and along the periphery, giving rise to a second growth phase. Undecylprodigiosin and actinorhodin antibiotics are produced by this second mycelium but not by the first one. Cell density dictates how the culture will behave in terms of differentiation processes and antibiotic production. When diluted inocula are used, the growth arrest phase, emergence of a second mycelium, and antibiotic production are delayed. Moreover, pellets are less abundant and have larger diameters than in dense cultures. This work is the first to report on the relationship between differentiation processes and secondary metabolite production in submerged Streptomyces cultures.Streptomyces is a soil bacterium that produces numerous clinically useful antibiotics (1, 54, 66), as well as many molecules that affect eukaryotic systems, such as inducers of eukaryotic cellular differentiation, inducers and inhibitors of apoptosis (59), and protein C kinase inhibitors with antitumor activity (such as staurosporine and others) (48, 57). Moreover, its remarkably complex developmental cycle makes this microorganism an interesting subject for study. The traditional developmental cycle of this bacterium describes two differentiated mycelial structures, a substrate (vegetative) mycelium and an aerial (reproductive) mycelium (10,25,33). In the substrate mycelium, septa are thought to be widely spaced and to define compartments containing several nucleoids (10, 63). After a short growth arrest phase characterized by reduced macromolecular synthesis (25), aerial hyphae develop from simple branching from substrate mycelium (29). Finally, the tips of the aerial mycelium differentiate into hydrophobic spore chains (8). Recently, we have been able to extend what is known about the developmental cycle in surface confluent cultures a great deal. Our main contribution has been to reveal the existence of a very young compartmentalized mycelium that dies following an orderly pattern, leaving alternating live and dead segments in the same hypha (37). Subsequently, the remaining live mycelium grows in successive waves that vary according to the density of the ...

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Section: Discussionmentioning

confidence: 90%

Mycelium Differentiation and Antibiotic Production in Submerged Cultures ofStreptomyces coelicolor

Manteca

Álvarez

Salazar

et al. 2008

Appl Environ Microbiol

142

162

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“…The developmental database recorded changes in a culture radiolabeled at 16 different time points (12,16,20,24,26,28,30,32,36,40,44,48,54,60,66, and 72 h; Fig. 1) (14).…”

Section: Methodsmentioning

confidence: 99%

“…Similar growth kinetics have been observed in liquid cultures of various Streptomyces species. The T phase has been associated with the activation of antibiotic biosynthetic genes (16) and regulatory elements needed for antibiotic-induced expression of a multidrug resistance gene (26), a starvation response indicated by the accumulation of ppGpp (16), and decreases in the rates of synthesis of ribosomal proteins (1). When thermal stress was applied to these cultures at different times during growth, the levels of thermal induction attained were closely related to growth stage, supporting the notion that developmental and thermal induction of this stress stimulon has common control elements (25).…”

mentioning

confidence: 99%

Developmental Control of Stress Stimulons in Streptomyces coelicolor Revealed by Statistical Analyses of Global Gene Expression Patterns

Vohradský

Dale

et al. 2000

J Bacteriol

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Stress-induced regulatory networks coordinated with a procaryotic developmental program were revealed by two-dimensional gel analyses of global gene expression. Four developmental stages were identified by their distinctive protein synthesis patterns using principal component analysis. Statistical analyses focused on five stress stimulons (induced by heat, cold, salt, ethanol, or antibiotic shock) and their synthesis during development. Unlike other bacteria, for which various stresses induce expression of similar sets of protein spots, in Streptomyces coelicolor heat, salt, and ethanol stimulons were composed of independent sets of proteins. This suggested independent control by different physiological stress signals and their corresponding regulatory systems. These stress proteins were also under developmental control. Cluster analysis of stress protein synthesis profiles identified 10 different developmental patterns or "synexpression groups." Proteins induced by cold, heat, or salt shock were enriched in three developmental synexpression groups. In addition, certain proteins belonging to the heat and salt shock stimulons were coregulated during development. Thus, stress regulatory systems controlling these stimulons were implicated as integral parts of the developmental program. This correlation suggested that thermal shock and salt shock stress response regulatory systems either allow the cell to adapt to stresses associated with development or directly control the developmental program.

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“…Streptomyces species, in particular, have been the object of considerable attention because these gram-positive bacteria are responsible for the production of the majority of commercially important antibiotics. Uncharacterized regulators designated Pip proteins have been proposed to be involved in the regulation of drug transport genes in a range of Streptomyces species (187,188). Isolation of the Pip protein from the genetically well-defined Streptomyces coelicolor indicated that it was a TetR family repressor that regulates the expression of the MFS antiporter Ptr, which confers resistance to the antibiotic pristinamycin I (34).…”

Section: Drug Transporter Expression In Other Pathogens and Antibiotimentioning

confidence: 99%

Regulation of Bacterial Drug Export Systems

Grkovic

Brown

Skurray

2002

Microbiol Mol Biol Rev

359

339

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The active transport of toxic compounds by membrane-bound efflux proteins is becoming an increasingly frequent mechanism by which cells exhibit resistance to therapeutic drugs. This review examines the regulation of bacterial drug efflux systems, which occurs primarily at the level of transcription. Investigations into these regulatory networks have yielded a substantial volume of information that has either not been forthcoming from or complements that obtained by analysis of the transport proteins themselves. Several local regulatory proteins, including the activator BmrR from Bacillus subtilis and the repressors QacR from Staphylococcus aureus and TetR and EmrR from Escherichia coli, have been shown to mediate increases in the expression of drug efflux genes by directly sensing the presence of the toxic substrates exported by their cognate pump. This ability to bind transporter substrates has permitted detailed structural information to be gathered on protein-antimicrobial agent-ligand interactions. In addition, bacterial multidrug efflux determinants are frequently controlled at a global level and may belong to stress response regulons such as E. coli mar, expression of which is controlled by the MarA and MarR proteins. However, many regulatory systems are ill-adapted for detecting the presence of toxic pump substrates and instead are likely to respond to alternative signals related to unidentified physiological roles of the transporter. Hence, in a number of important pathogens, regulatory mutations that result in drug transporter overexpression and concomitant elevated antimicrobial resistance are often observed

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Stress‐activated expression of a Streptomyces pristinaespiralis multidrug resistance gene (ptr) in various Streptomyces spp. and Escherichia coli

Cited by 32 publications

References 43 publications

Mycelium Differentiation and Antibiotic Production in Submerged Cultures ofStreptomyces coelicolor

Mycelium Differentiation and Antibiotic Production in Submerged Cultures ofStreptomyces coelicolor

Developmental Control of Stress Stimulons in Streptomyces coelicolor Revealed by Statistical Analyses of Global Gene Expression Patterns

Regulation of Bacterial Drug Export Systems

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