Natural competence

Last updated
Natural competence. 1-Bacterial cell DNA 2-Bacterial cell plasmids 3-Sex pili 4-Plasmid of foreign DNA from a dead cell 5-Bacterial cell restriction enzyme 6-Unwound foreign plasmid 7-DNA ligase I: A plasmid of foreign DNA from a dead cell is intercepted by the sex pili of a naturally competent bacterial cell. II: The foreign plasmid is transduced through the sex pili into the bacterial cell, where it is processed by bacterial cell restriction enzymes. The restriction enzymes break the foreign plasmid into a strand of nucleotides that can be added to the bacterial DNA. III: DNA ligase integrates the foreign nucleotides into the bacterial cell DNA. IV: Recombination is complete and the foreign DNA has integrated into the original bacterial cell's DNA and will continue to be a part of it when the bacterial cell replicates next. Natural Competence Drawing.svg
Natural competence.
1-Bacterial cell DNA
2-Bacterial cell plasmids
3-Sex pili
4-Plasmid of foreign DNA from a dead cell
5-Bacterial cell restriction enzyme
6-Unwound foreign plasmid
7-DNA ligase
I: A plasmid of foreign DNA from a dead cell is intercepted by the sex pili of a naturally competent bacterial cell.
II: The foreign plasmid is transduced through the sex pili into the bacterial cell, where it is processed by bacterial cell restriction enzymes. The restriction enzymes break the foreign plasmid into a strand of nucleotides that can be added to the bacterial DNA.
III: DNA ligase integrates the foreign nucleotides into the bacterial cell DNA.
IV: Recombination is complete and the foreign DNA has integrated into the original bacterial cell's DNA and will continue to be a part of it when the bacterial cell replicates next.

In microbiology, genetics, cell biology, and molecular biology, competence is the ability of a cell to alter its genetics by taking up extracellular ("naked") DNA from its environment in the process called transformation. Competence may be differentiated between natural competence, a genetically specified ability of bacteria which is thought to occur under natural conditions as well as in the laboratory, and induced or artificial competence, which arises when cells in laboratory cultures are treated to make them transiently permeable to DNA. Competence allows for rapid adaptation and DNA repair of the cell. This article primarily deals with natural competence in bacteria, although information about artificial competence is also provided.

Contents

History

Natural competence was discovered by Frederick Griffith in 1928, when he showed that a preparation of killed cells of a pathogenic bacterium contained something that could transform related non-pathogenic cells into the pathogenic type. In 1944 Oswald Avery, Colin MacLeod, and Maclyn McCarty demonstrated that this 'transforming factor' was pure DNA [1] . This was the first compelling evidence that DNA carries the genetic information of the cell.

Since then, natural competence has been studied in a number of different bacteria, particularly Bacillus subtilis , Streptococcus pneumoniae (Griffith's "pneumococcus"), Neisseria gonorrhoeae , Haemophilus influenzae and members of the Acinetobacter genus. Areas of active research include the mechanisms of DNA transport, the regulation of competence in different bacteria, and the evolutionary function of competence.

Mechanisms of DNA uptake

In the laboratory, DNA is provided by the researcher, often as a genetically engineered fragment or plasmid. During uptake, DNA is transported across the cell membrane(s), and the cell wall if one is present. Once the DNA is inside the cell it may be degraded to nucleotides, which are reused for DNA replication and other metabolic functions. Alternatively it may be recombined into the cell's genome by its DNA repair enzymes. If this recombination changes the cell's genotype the cell is said to have been transformed. Artificial competence and transformation are used as research tools in many organisms (see Transformation (genetics) ). [2]

In almost all naturally competent bacteria components of extracellular filaments called type IV pili (a type of fimbria) bind extracellular double stranded DNA. The DNA is then translocated across the membrane (or membranes for gram negative bacteria) through multi-component protein complexes driven by the degradation of one strand of the DNA. Single stranded DNA in the cell is bound by a well-conserved protein, DprA, which loads the DNA onto RecA, which mediates homologous recombination through the classic DNA repair pathway. [3]

Regulation of competence

In laboratory cultures, natural competence is usually tightly regulated and often triggered by nutritional shortages or adverse conditions. However the specific inducing signals and regulatory machinery are much more variable than the uptake machinery, and little is known about the regulation of competence in the natural environments of these bacteria. [4] Transcription factors have been discovered which regulate competence; an example is sxy (also known as tfoX) which has been found to be regulated in turn by a 5' non-coding RNA element. [5] In bacteria capable of forming spores, conditions inducing sporulation often overlap with those inducing competence. Thus cultures or colonies containing sporulating cells often also contain competent cells. Recent research by Süel et al. has identified an excitable core module of genes which can explain entry into and exit from competence when cellular noise is taken into account. [6]

Most competent bacteria are thought to take up all DNA molecules with roughly equal efficiencies, but bacteria in the families Neisseriaceae and Pasteurellaceae preferentially take up DNA fragments containing short DNA sequences, termed DNA uptake sequence (DUS) in Neisseriaceae and uptake signal sequence (USS) in Pasteurellaceae, that are very frequent in their own genomes. Neisserial genomes contain thousands of copies of the preferred sequence GCCGTCTGAA, and Pasteurellacean genomes contain either AAGTGCGGT or ACAAGCGGT. [2] [7]

Evolutionary functions and consequences of competence

Most proposals made for the primary evolutionary function of natural competence as a part of natural bacterial transformation fall into three categories: (1) the selective advantage of genetic diversity; (2) DNA uptake as a source of nucleotides (DNA as “food”); and (3) the selective advantage of a new strand of DNA to promote homologous recombinational repair of damaged DNA (DNA repair). A secondary suggestion has also been made, noting the occasional advantage of horizontal gene transfer.

Hypothesis of genetic diversity

Arguments to support genetic diversity as the primary evolutionary function of sex (including bacterial transformation) are given by Barton and Charlesworth [8] and by Otto and Gerstein. [9] However, the theoretical difficulties associated with the evolution of sex suggest that sex for genetic diversity is problematic. Specifically with respect to bacterial transformation, competence requires the high cost of a global protein synthesis switch, with, for example, more than 16 genes that are switched on only during competence of Streptococcus pneumoniae. [10] However, since bacteria tend to grow in clones, the DNA available for transformation would generally have the same genotype as that of the recipient cells. Thus, there is always a high cost in protein expression without, in general, an increase in diversity. Other differences between competence and sex have been considered in models of the evolution of genes causing competence; these models found that competence's postulated recombinational benefits were even more elusive than those of sex. [11]

Hypothesis of DNA as food

The second hypothesis, DNA as food, relies on the fact that cells that take up DNA inevitably acquire the nucleotides the DNA consists of, and, because nucleotides are needed for DNA and RNA synthesis and are expensive to synthesize, these may make a significant contribution to the cell's energy budget. [12] Some naturally competent bacteria also secrete nucleases into their surroundings, and all bacteria can take up the free nucleotides these nucleases generate from environmental DNA. [13] The energetics of DNA uptake are not understood in any system, so it is difficult to compare the efficiency of nuclease secretion to that of DNA uptake and internal degradation. In principle the cost of nuclease production and the uncertainty of nucleotide recovery must be balanced against the energy needed to synthesize the uptake machinery and to pull DNA in. Other important factors are the likelihoods that nucleases and competent cells will encounter DNA molecules, the relative inefficiencies of nucleotide uptake from the environment and from the periplasm (where one strand is degraded by competent cells), and the advantage of producing ready-to-use nucleotide monophosphates from the other strand in the cytoplasm. Another complicating factor is the self-bias of the DNA uptake systems of species in the family Pasteurellaceae and the genus Neisseria, which could reflect either selection for recombination or for mechanistically efficient uptake. [14] [15]

Hypothesis of repair of DNA damage

In bacteria, the problem of DNA damage is most pronounced during periods of stress, particularly oxidative stress, that occur during crowding or starvation conditions. Under such conditions there is often only a single chromosome present. The finding that some bacteria induce competence under such stress conditions, supports the third hypothesis, that transformation exists to permit DNA repair. In experimental tests, bacterial cells exposed to agents damaging their DNA, and then undergoing transformation, survived better than cells exposed to DNA damage that did not undergo transformation (Hoelzer and Michod, 1991). [16] In addition, competence to undergo transformation is often inducible by known DNA damaging agents (reviewed by Michod et al., 2008 and Bernstein et al., 2012). [17] [18] Thus, a strong short-term selective advantage for natural competence and transformation would be its ability to promote homologous recombinational DNA repair under conditions of stress. Such stress conditions might be incurred during bacterial infection of a susceptible host. Consistent with this idea, Li et al. [19] reported that, among different highly transformable S. pneumoniae isolates, nasal colonization fitness and virulence (lung infectivity) depends on an intact competence system.

A counter argument was made based on the 1993 report of Redfield who found that single-stranded and double-stranded damage to chromosomal DNA did not induce or enhance competence or transformation in B. subtilis or H. influenzae, suggesting that selection for repair has played little or no role in the evolution of competence in these species [20]

However more recent evidence indicates that competence for transformation is, indeed, specifically induced by DNA damaging conditions. For instance, Claverys et al. in 2006 [21] showed that the DNA damaging agents mitomycin C (a DNA cross-linking agent) and fluoroquinolone (a topoisomerase inhibitor that causes double-strand breaks) induce transformation in Streptococcus pneumoniae. In addition, Engelmoer and Rozen [22] in 2011 demonstrated that in S. pneumoniae transformation protects against the bactericidal effect of mitomycin C. Induction of competence further protected against the antibiotics kanomycin and streptomycin. [21] [22] Although these aminoglycoside antibiotics were previously regarded as non-DNA damaging, recent studies in 2012 of Foti et al. [23] showed that a substantial portion of their bactericidal activity results from release of the hydroxyl radical and induction of DNA damages, including double-strand breaks.

Dorer et al., [24] in 2010, showed that ciprofloxacin, which interacts with DNA gyrase and causes production of double-strand breaks, induces expression of competence genes in Helicobacter pylori, leading to increased transformation. In 2011 studies of Legionella pneumophila, Charpentier et al. [25] tested 64 toxic molecules to determine which ones induce competence. Only six of these molecules, all DNA damaging agents, strongly induced competence. These molecules were norfloxacin, ofloxacin and nalidixic acid (inhibitors of DNA gyrase that produce double strand breaks [26] ), mitomycin C (which produces inter-strand cross-links), bicyclomycin (causes single- and double-strand breaks [27] ), and hydroxyurea (causes oxidation of DNA bases [28] ). Charpentier et al. [25] also showed that UV irradiation induces competence in L. pneumophila and further suggested that competence for transformation evolved as a response to DNA damage.

Horizontal gene transfer

A long-term advantage may occasionally be conferred by occasional instances of horizontal gene transfer also called lateral gene transfer, (which might result from non-homologous recombination after competence is induced), that could provide for antibiotic resistance or other advantages.

Regardless of the nature of selection for competence, the composite nature of bacterial genomes provides abundant evidence that the horizontal gene transfer caused by competence contributes to the genetic diversity that makes evolution possible.

See also

Related Research Articles

<span class="mw-page-title-main">Bacterial conjugation</span> Method of bacterial gene transfer

Bacterial conjugation is the transfer of genetic material between bacterial cells by direct cell-to-cell contact or by a bridge-like connection between two cells. This takes place through a pilus. It is a parasexual mode of reproduction in bacteria.

<span class="mw-page-title-main">Chromosomal crossover</span> Cellular process

Chromosomal crossover, or crossing over, is the exchange of genetic material during sexual reproduction between two homologous chromosomes' non-sister chromatids that results in recombinant chromosomes. It is one of the final phases of genetic recombination, which occurs in the pachytene stage of prophase I of meiosis during a process called synapsis. Synapsis begins before the synaptonemal complex develops and is not completed until near the end of prophase I. Crossover usually occurs when matching regions on matching chromosomes break and then reconnect to the other chromosome.

<span class="mw-page-title-main">Genetic recombination</span> Production of offspring with combinations of traits that differ from those found in either parent

Genetic recombination is the exchange of genetic material between different organisms which leads to production of offspring with combinations of traits that differ from those found in either parent. In eukaryotes, genetic recombination during meiosis can lead to a novel set of genetic information that can be further passed on from parents to offspring. Most recombination occurs naturally and can be classified into two types: (1) interchromosomal recombination, occurring through independent assortment of alleles whose loci are on different but homologous chromosomes ; & (2) intrachromosomal recombination, occurring through crossing over.

<span class="mw-page-title-main">Horizontal gene transfer</span> Type of nonhereditary genetic change

Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between organisms other than by the ("vertical") transmission of DNA from parent to offspring (reproduction). HGT is an important factor in the evolution of many organisms. HGT is influencing scientific understanding of higher order evolution while more significantly shifting perspectives on bacterial evolution.

<span class="mw-page-title-main">Molecular genetics</span> Scientific study of genes at the molecular level

Molecular genetics is a branch of biology that addresses how differences in the structures or expression of DNA molecules manifests as variation among organisms. Molecular genetics often applies an "investigative approach" to determine the structure and/or function of genes in an organism's genome using genetic screens. 

<i>Streptococcus pneumoniae</i> Species of bacterium

Streptococcus pneumoniae, or pneumococcus, is a Gram-positive, spherical bacteria, alpha-hemolytic member of the genus Streptococcus. They are usually found in pairs (diplococci) and do not form spores and are non motile. As a significant human pathogenic bacterium S. pneumoniae was recognized as a major cause of pneumonia in the late 19th century, and is the subject of many humoral immunity studies.

<span class="mw-page-title-main">Transformation (genetics)</span> Genetic alteration of a cell by uptake of genetic material from the environment

In molecular biology and genetics, transformation is the genetic alteration of a cell resulting from the direct uptake and incorporation of exogenous genetic material from its surroundings through the cell membrane(s). For transformation to take place, the recipient bacterium must be in a state of competence, which might occur in nature as a time-limited response to environmental conditions such as starvation and cell density, and may also be induced in a laboratory.

<span class="mw-page-title-main">Evolution of sexual reproduction</span> How sexually reproducing multicellular organisms could have evolved from a common ancestor species

Sexual reproduction is an adaptive feature which is common to almost all multicellular organisms and various unicellular organisms. Currently, the adaptive advantage of sexual reproduction is widely regarded as a major unsolved problem in biology. As discussed below, one prominent theory is that sex evolved as an efficient mechanism for producing variation, and this had the advantage of enabling organisms to adapt to changing environments. Another prominent theory, also discussed below, is that a primary advantage of outcrossing sex is the masking of the expression of deleterious mutations. Additional theories concerning the adaptive advantage of sex are also discussed below. Sex does, however, come with a cost. In reproducing asexually, no time nor energy needs to be expended in choosing a mate and, if the environment has not changed, then there may be little reason for variation, as the organism may already be well-adapted. However, very few environments have not changed over the millions of years that reproduction has existed. Hence it is easy to imagine that being able to adapt to changing environment imparts a benefit. Sex also halves the amount of offspring a given population is able to produce. Sex, however, has evolved as the most prolific means of species branching into the tree of life. Diversification into the phylogenetic tree happens much more rapidly via sexual reproduction than it does by way of asexual reproduction.

<i>Bacillus subtilis</i> Catalase-positive bacterium

Bacillus subtilis, known also as the hay bacillus or grass bacillus, is a Gram-positive, catalase-positive bacterium, found in soil and the gastrointestinal tract of ruminants, humans and marine sponges. As a member of the genus Bacillus, B. subtilis is rod-shaped, and can form a tough, protective endospore, allowing it to tolerate extreme environmental conditions. B. subtilis has historically been classified as an obligate aerobe, though evidence exists that it is a facultative anaerobe. B. subtilis is considered the best studied Gram-positive bacterium and a model organism to study bacterial chromosome replication and cell differentiation. It is one of the bacterial champions in secreted enzyme production and used on an industrial scale by biotechnology companies.

<i>Mycobacterium smegmatis</i> Species of bacterium

Mycobacterium smegmatis is an acid-fast bacterial species in the phylum Actinomycetota and the genus Mycobacterium. It is 3.0 to 5.0 µm long with a bacillus shape and can be stained by Ziehl–Neelsen method and the auramine-rhodamine fluorescent method. It was first reported in November 1884 by Lustgarten, who found a bacillus with the staining appearance of tubercle bacilli in syphilitic chancres. Subsequent to this, Alvarez and Tavel found organisms similar to that described by Lustgarten also in normal genital secretions (smegma). This organism was later named M. smegmatis.

<span class="mw-page-title-main">RecA</span> DNA repair protein

RecA is a 38 kilodalton protein essential for the repair and maintenance of DNA. A RecA structural and functional homolog has been found in every species in which one has been seriously sought and serves as an archetype for this class of homologous DNA repair proteins. The homologous protein is called RAD51 in eukaryotes and RadA in archaea.

<span class="mw-page-title-main">Homologous recombination</span> Genetic recombination between identical or highly similar strands of genetic material

Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids.

Recombinases are genetic recombination enzymes.

Microbial genetics is a subject area within microbiology and genetic engineering. Microbial genetics studies microorganisms for different purposes. The microorganisms that are observed are bacteria, and archaea. Some fungi and protozoa are also subjects used to study in this field. The studies of microorganisms involve studies of genotype and expression system. Genotypes are the inherited compositions of an organism. Genetic Engineering is a field of work and study within microbial genetics. The usage of recombinant DNA technology is a process of this work. The process involves creating recombinant DNA molecules through manipulating a DNA sequence. That DNA created is then in contact with a host organism. Cloning is also an example of genetic engineering.

Calcium chloride (CaCl2) transformation is a laboratory technique in prokaryotic (bacterial) cell biology. The addition of calcium chloride to a cell suspension promotes the binding of plasmid DNA to lipopolysaccharides (LPS). Positively charged calcium ions attract both the negatively charged DNA backbone and the negatively charged groups in the LPS inner core. The plasmid DNA can then pass into the cell upon heat shock, where chilled cells (+4 degrees Celsius) are heated to a higher temperature (+42 degrees Celsius) for a short time.

<span class="mw-page-title-main">Sexual reproduction</span> Reproduction process that creates a new organism by combining the genetic material of two organisms

Sexual reproduction is a type of reproduction that involves a complex life cycle in which a gamete with a single set of chromosomes combines with another gamete to produce a zygote that develops into an organism composed of cells with two sets of chromosomes (diploid). This is typical in animals, though the number of chromosome sets and how that number changes in sexual reproduction varies, especially among plants, fungi, and other eukaryotes.

The origin and function of meiosis are currently not well understood scientifically, and would provide fundamental insight into the evolution of sexual reproduction in eukaryotes. There is no current consensus among biologists on the questions of how sex in eukaryotes arose in evolution, what basic function sexual reproduction serves, and why it is maintained, given the basic two-fold cost of sex. It is clear that it evolved over 1.2 billion years ago, and that almost all species which are descendants of the original sexually reproducing species are still sexual reproducers, including plants, fungi, and animals.

<span class="mw-page-title-main">Genetic engineering techniques</span> Methods used to change the DNA of organisms

Genetic engineering techniques allow the modification of animal and plant genomes. Techniques have been devised to insert, delete, and modify DNA at multiple levels, ranging from a specific base pair in a specific gene to entire genes. There are a number of steps that are followed before a genetically modified organism (GMO) is created. Genetic engineers must first choose what gene they wish to insert, modify, or delete. The gene must then be isolated and incorporated, along with other genetic elements, into a suitable vector. This vector is then used to insert the gene into the host genome, creating a transgenic or edited organism.

Bacterial recombination is a type of genetic recombination in bacteria characterized by DNA transfer from one organism called donor to another organism as recipient. This process occurs in three main ways:

<span class="mw-page-title-main">Competence factor</span>

The ability of a cell to successfully incorporate exogenous DNA, or competency, is determined by competence factors. These factors consist of certain cell surface proteins and transcription factors that induce the uptake of DNA.

References

  1. ↑ Avery OT, Macleod CM, McCarty M (1944). "Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types". J. Exp. Med. 79 (2): 137–58. doi:10.1084/jem.79.2.137. PMC   2135445 . PMID   19871359.
  2. 1 2 Chen I, Dubnau D (2004). "DNA uptake during bacterial transformation". Nat. Rev. Microbiol. 2 (3): 241–9. doi:10.1038/nrmicro844. PMID   15083159. S2CID   205499369.
  3. ↑ Johnston C, Martin B, Fichant G, Polard P, Claverys J (2014). "Bacterial transformation: distribution, shared mechanisms and divergent control". Nat. Rev. Microbiol. 12 (3): 181–96. doi:10.1038/nrmicro3199. PMID   24509783. S2CID   23559881.
  4. ↑ Solomon JM, Grossman AD (1996). "Who's competent and when: regulation of natural genetic competence in bacteria". Trends Genet. 12 (4): 150–5. doi:10.1016/0168-9525(96)10014-7. PMID   8901420.
  5. ↑ Redfield RJ (September 1991). "sxy-1, a Haemophilus influenzae mutation causing greatly enhanced spontaneous competence". J. Bacteriol. 173 (18): 5612–8. doi:10.1128/jb.173.18.5612-5618.1991. PMC   208288 . PMID   1653215.
  6. ↑ Süel GM, Garcia-Ojalvo J, Liberman LM, Elowitz MB (2006). "An excitable gene regulatory circuit induces transient cellular differentiation" (PDF). Nature. 440 (7083): 545–50. Bibcode:2006Natur.440..545S. doi:10.1038/nature04588. PMID   16554821. S2CID   4327745.
  7. ↑ Findlay, WA; Redfield, RJ (2009). "Coevolution of DNA uptake sequences and bacterial proteomes". Genome Biology and Evolution. 1: 45–55. doi:10.1093/gbe/evp005. PMC   2817400 . PMID   20333176.
  8. ↑ Barton NH, Charlesworth B (1998). "Why sex and recombination?". Science. 281 (5385): 1986–1990. doi:10.1126/science.281.5385.1986. PMID   9748151.
  9. ↑ Otto SP, Gerstein AC (Aug 2006). "Why have sex? The population genetics of sex and recombination". Biochem Soc Trans. 34 (Pt 4): 519–522. doi:10.1042/BST0340519. PMID   16856849.
  10. ↑ Peterson S, Cline RT, Tettelin H, Sharov V, Morrison DA (Nov 2000). "Gene expression analysis of the Streptococcus pneumoniae competence regulons by use of DNA microarrays". J. Bacteriol. 182 (21): 6192–6202. doi:10.1128/JB.182.21.6192-6202.2000. PMC   94756 . PMID   11029442.
  11. ↑ Redfield R (1988). "Is sex with dead cells ever better than no sex at all?". Genetics. 119 (1): 213–21. doi:10.1093/genetics/119.1.213. PMC   1203342 . PMID   3396864.
  12. ↑ Redfield RJ (2001). "Do bacteria have sex?". Nat. Rev. Genet. 2 (8): 634–9. doi:10.1038/35084593. PMID   11483988. S2CID   5465846.
  13. ↑ Dubnau D (1999). "DNA uptake in bacteria". Annu Rev Microbiol. 53 (1): 217–44. doi:10.1146/annurev.micro.53.1.217. PMID   10547691.
  14. ↑ Maughan H (2010). "Bacterial DNA uptake sequences can accumulate by molecular drive alone". Genetics. 186 (2): 613–27. doi:10.1534/genetics.110.119438. PMC   2954483 . PMID   20628039.
  15. ↑ Redfield R, Schrag M, Dead A (1997). "The evolution of bacterial transformation: sex with poor relations". Genetics. 146 (1): 27–38. doi:10.1093/genetics/146.1.27. PMC   1207942 . PMID   9135998.
  16. ↑ Hoelzer MA, Michod RE (1991). "DNA repair and the evolution of transformation in Bacillus subtilis. III. Sex with damaged DNA". Genetics. 128 (2): 215–23. doi:10.1093/genetics/128.2.215. PMC   1204460 . PMID   1906416.
  17. ↑ Michod RE, Bernstein H, Nedelcu AM (2008). "Adaptive value of sex in microbial pathogens". Infect Genet Evol. 8 (3): 267–85. doi:10.1016/j.meegid.2008.01.002. PMID   18295550. http://www.hummingbirds.arizona.edu/Faculty/Michod/Downloads/IGE%20review%20sex.pdf
  18. ↑ Bernstein, Harris; Carol Bernstein; Richard E. Michod (2012). "Chapter 1 - DNA Repair as the Primary Adaptive Function of Sex in Bacteria and Eukaryotes". DNA Repair: New Research. NOVA Publishers. pp. 1–50. ISBN   978-1-62100-756-2. Archived from the original on 2013-10-29. Retrieved 2012-04-13. https://www.novapublishers.com/catalog/product_info.php?products_id=31918
  19. ↑ Li G, Liang Z, Wang X, Yang Y, Shao Z, Li M, Ma Y, Qu F, Morrison DA, Zhang JR (2016). "Addiction of Hypertransformable Pneumococcal Isolates to Natural Transformation for In Vivo Fitness and Virulence". Infect. Immun. 84 (6): 1887–901. doi:10.1128/IAI.00097-16. PMC   4907133 . PMID   27068094.
  20. ↑ Redfield R (1993). "Evolution of natural transformation: testing the DNA repair hypothesis in Bacillus subtilis and Haemophilus influenzae". Genetics. 133 (4): 755–61. doi:10.1093/genetics/133.4.755. PMC   1205397 . PMID   8462839.
  21. 1 2 Claverys, JP; Prudhomme, M; Martin, B (2006). "Induction of competence regulons as a general response to stress in gram-positive bacteria". Annu Rev Microbiol. 60 (1): 451–475. doi:10.1146/annurev.micro.60.080805.142139. PMID   16771651.
  22. 1 2 Engelmoer, D J; Rozen, D E (2011). "Competence increases survival during stress in Streptococcus pneumoniae". Evolution. 65 (12): 3475–3485. doi: 10.1111/j.1558-5646.2011.01402.x . PMID   22133219.
  23. ↑ Foti, JJ; Devadoss, B; Winkler, JA; Collins, JJ; Walker, GC (2012). "Oxidation of the guanine nucleotide pool underlies cell death by bactericidal antibiotics". Science. 336 (6079): 315–319. Bibcode:2012Sci...336..315F. doi:10.1126/science.1219192. PMC   3357493 . PMID   22517853.
  24. ↑ Dorer, MS; Fero, J; Salama, NR (2010). "DNA damage triggers genetic exchange in Helicobacter pylori". PLOS Pathog. 6 (7): e1001026. doi: 10.1371/journal.ppat.1001026 . PMC   2912397 . PMID   20686662.
  25. 1 2 Charpentier, X; Kay, E; Schneider, D; Shuman, HA (2011). "Antibiotics and UV radiation induce competence for natural transformation in Legionella pneumophila". J Bacteriol. 193 (5): 1114–1121. doi:10.1128/JB.01146-10. PMC   3067580 . PMID   21169481.
  26. ↑ Albertini, S; Chételat, A A; Miller, B; Muster, W; Pujadas, E; Strobel, R; Gocke, E (1995). "Genotoxicity of 17 gyrase- and four mammalian topoisomerase II-poisons in prokaryotic and eukaryotic test systems". Mutagenesis. 10 (4): 343–351. doi:10.1093/mutage/10.4.343. PMID   7476271.
  27. ↑ Washburn, R S; Gottesman, M E (2011). "Transcription termination maintains chromosome integrity". Proc Natl Acad Sci U S A. 108 (2): 792–7. Bibcode:2011PNAS..108..792W. doi: 10.1073/pnas.1009564108 . PMC   3021005 . PMID   21183718.
  28. ↑ Sakano, K; Oikawa, S; Hasegawa, K; Kawanishi, S (2001). "Hydroxyurea induces site-specific DNA damage via formation of hydrogen peroxide and nitric oxide". Jpn J Cancer Res. 92 (11): 1166–1174. doi:10.1111/j.1349-7006.2001.tb02136.x. PMC   5926660 . PMID   11714440.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.