Genome plasticity is governed by double strand break DNA repair in Streptomyces

Hoff, Grégory; Bertrand, Claire; Piotrowski, Emilie; Thibessard, Annabelle; Leblond, Pierre

doi:10.1038/s41598-018-23622-w

Cited by 67 publications

(73 citation statements)

References 50 publications

(58 reference statements)

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“…Actinobacterial genomes readily undergo rearrangements, whereby more than 1 Mb of genomic DNA can be lost [18, 21, 29]. Here, we provide evidence that protoplast formation and regeneration in K. viridifaciens can lead to profound genomic rearrangements in the chromosome as well as loss of (large parts of) the megaplasmid KVP1.…”

Section: Discussionmentioning

confidence: 79%

“…The frequency of aberrant phenotypes after protoplast regeneration is higher than the phenotypic heterogeneity obtained after outgrowth of spores, which typically is in the order of 1% [18, 21, 29, 33, 36, 37]. An explanation for the high frequency of aberrant mutants in colonies arising after protoplasting may relate to the activation of transposable elements contained in the terminal regions of the chromosome and/or the KVP1 plasmid.…”

Section: Discussionmentioning

confidence: 99%

“…The chromosomal ends are genetically unstable, and readily undergo large (up to 2 Mb) DNA rearrangements. Such rearrangements can lead to circularization of the chromosome, exchange of chromosomal arms or the formation of hybrid chromosomes due to recombination between the linear plasmids and the chromosome [18]. This wide range of genomic rearrangements is believed to be caused by transposition or homologous recombination, occurring actively within the chromosome or between the chromosome and linear plasmids [19].…”

Section: Introductionmentioning

confidence: 99%

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Genome rearrangements and megaplasmid loss in the filamentous bacteriumKitasatospora viridifaciensare associated with protoplast formation and regeneration

Ramijan

Zhang

Wezel

et al. 2019

Preprint

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20Filamentous Actinobacteria are multicellular bacteria with linear replicons. Kitasatospora 21 viridifaciens DSM 40239 contains a linear 7.8 Mb chromosome and an autonomously 22 replicating plasmid KVP1 of 1.7 Mb. Here we show that lysozyme-induced protoplast 23 formation of the multinucleated mycelium of K. viridifaciens drives morphological diversity. 24Characterization and sequencing of an individual revertant colony that had lost the ability to 25 differentiate revealed that the strain had not only lost most of KVP1 but also carried lesions 26 in the right arm of the chromosome. Strikingly, the lesion sites were preceded by insertion 27 sequence elements, suggesting that the rearrangements may have been caused by 28 replicative transposition and homologous recombination between both replicons. These 29 data indicate that protoplast formation is a stressful process that can lead to profound 30 genetic changes. 31 34 metabolites are mostly used as weapons that provide protection against other 35 microorganisms and phages in the environment [1][2][3]. This is particularly useful for 36 filamentous organisms, given that they generally lack the ability to make flagella for escaping 37 dangerous situations. In addition, these bacteria are able to generate resistant spores that 38 can invade new environments after their dispersal. Germination of spores leads to the 39 formation of 1-2 germ tubes, which grow by tip extension, thereby establishing filamentous 40 cells called hyphae. Branching of hyphae leads to the formation of a multinucleated 41 vegetative mycelium, which forages and acquires nutrients by decomposing polymeric 42 substances. Stressful conditions (such as nutrient depletion) induce program cell death 43 (PCD) of the mycelium, which in turn triggers morphological and chemical differentiation [4].44 This developmental transition leads to the formation of specialized hyphae that grow into the 45 air, and the onset of production of a suite of bioactive compounds [5]. Eventually, the aerial 46 hyphae metamorphose into chains of grey-pigmented spores. Mutants that are unable to 47 establish an aerial mycelium are called bald (bld), while those that are not capable to form 48 spores are called white (whi) after their whitish color [6, 7]. 49Genome mining has been instrumental for the revival of drug discovery [8, 9]. Many 50 of the biosynthetic gene clusters that specify bioactive natural products are contained on 51 giant linear plasmids [10-13]. Although linear replicons are rare in many bacterial taxa, they 52 are common in Actinobacteria [14, 15]. In fact, Streptomyces chromosomes (between 8 and 53 10 Mb in size) are also linear and typically comprise a "core region" containing the essential 54 genes, and two variable "arms" with lengths ranging from 1.5 Mb to 2.3 Mb [16]. Like linear 55 plasmids, the linear chromosomes are capped by terminal proteins bound to the 5' end of 56 the DNA [17]. The chromosomal ends are genetically unstable, and readily undergo large 57 (up to 2 Mb) DNA rearrangements. Such...

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genome rearrangements and megaplasmid loss in the filamentous bacteriumKitasatospora viridifaciensare associated with protoplast formation and regeneration

Ramijan

Zhang

Wezel

et al. 2019

Preprint

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“…♦ in M. tuberculosis denotes accessory actors involved in NHEJ, based on studies of their homologs in M. smegmatis coding for different LigD with mutated domain (see text). In S. ambofaciens , accessory actors involved in response to DNA damage are highlighted by an asterisk (Hoff et al , ; ). For the sake of clarity, only one dimer of Ku is shown at DNA ends and the ability of Ku to thread inward the DNA molecule has not been represented.…”

Section: Multiple Components Nhej Pathwaysmentioning

confidence: 99%

Bacterial NHEJ: a never ending story

Bertrand

Thibessard

Bruand

et al. 2019

Molecular Microbiology

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Double-strand breaks (DSBs) are the most detrimental DNA damage encountered by bacterial cells. DBSs can be repaired by homologous recombination thanks to the availability of an intact DNA template or by Non-Homologous End Joining (NHEJ) when no intact template is available. Bacterial NHEJ is performed by sets of proteins of growing complexity from Bacillus subtilis and Mycobacterium tuberculosis to Streptomyces and Sinorhizobium meliloti . Here, we discuss the contribution of these models to the understanding of the bacterial NHEJ repair mechanism as well as the involvement of NHEJ partners in other DNA repair pathways. The importance of NHEJ and of its complexity is discussed in the perspective of regulation through the biological cycle of the bacteria and in response to environmental stimuli. Finally, we consider the role of NHEJ in genome evolution, notably in horizontal gene transfer. Tel. +33 (0)3 72 74 51 43; Fax: +33 (0)3 83 68 44 99 # co-corresponding authors.

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“…However, the Streptomyces chromosome is very unstable and undergoes very large deletions spontaneously at rates higher than 0.1% of spores. This genetic instability affects different production of secondary metabolites, such as pigments and antibiotics [29,30].…”

Section: Fig 1 Time Course Of the Glycerol Concentration (Cgly) Andmentioning

confidence: 99%

Exploring the Optimization of UV Mutants of Streptomyces clavuligerus for Clavulanic Acid Production

Cruz-Hernández¹,

Vasconcelos²,

Teodoro³

et al. 2019

MRJI

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Streptomyces clavuligerus, initially described as a Cephamycin C producer, has been currently utilized to produce clavulanic acid (CA) which shows low antibiotic activity, being, however, a strong β-lactamase inhibitor, enzymes responsible for bacterial resistance to β-lactam antibiotics. Genetic improvement by physical and chemical agents is mandatory since, due to its genetic instability, industrial strains lose production capability making necessary a steady and frequent strain improvement and a screening procedure. The objective of this work was to obtain an increase in CA production in submerged cultures by utilizing mutants obtained by UV radiation of Original Research Articlewith this mutant, although a lower specific growth rate had been observed.

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Genome plasticity is governed by double strand break DNA repair in Streptomyces

Cited by 67 publications

References 50 publications

Genome rearrangements and megaplasmid loss in the filamentous bacteriumKitasatospora viridifaciensare associated with protoplast formation and regeneration

Genome rearrangements and megaplasmid loss in the filamentous bacteriumKitasatospora viridifaciensare associated with protoplast formation and regeneration

Bacterial NHEJ: a never ending story

Exploring the Optimization of UV Mutants of Streptomyces clavuligerus for Clavulanic Acid Production

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