A Trade-off between the Fitness Cost of Functional Integrases and Long-term Stability of Integrons
Horizontal gene transfer (HGT) plays a major role in bacterial microevolution as evident from the rapid emergence and spread of antimicrobial drug resistance. Few studies have however addressed the population dynamics of newly imported genetic elements after HGT. Here, we show that newly acquired class-1 integrons from Salmonella enterica serovar Typhimurium and Acinetobacter baumannii, free of associated transposable elements, strongly reduce host fitness in Acinetobacter baylyi. Insertional inactivation of the integron intI1 restored fitness, demonstrating that the observed fitness costs were due to the presence of an active integrase. The biological cost of harboring class-1 integrons was rapidly reduced during serial transfers due to intI1 frameshift mutations leading to inactivated integrases. We use a mathematical model to explore the conditions where integrons with functional integrases are maintained and conclude that environmental fluctuations and episodic selection is necessary for the maintenance of functional integrases. Taken together, the presented data suggest a trade-off between the ability to capture gene cassettes and long-term stability of integrons and provide an explanation for the frequent observation of inactive integron-integrases in bacterial populations.
Vyšlo v časopise:
A Trade-off between the Fitness Cost of Functional Integrases and Long-term Stability of Integrons. PLoS Pathog 8(11): e32767. doi:10.1371/journal.ppat.1003043
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1003043
Souhrn
Horizontal gene transfer (HGT) plays a major role in bacterial microevolution as evident from the rapid emergence and spread of antimicrobial drug resistance. Few studies have however addressed the population dynamics of newly imported genetic elements after HGT. Here, we show that newly acquired class-1 integrons from Salmonella enterica serovar Typhimurium and Acinetobacter baumannii, free of associated transposable elements, strongly reduce host fitness in Acinetobacter baylyi. Insertional inactivation of the integron intI1 restored fitness, demonstrating that the observed fitness costs were due to the presence of an active integrase. The biological cost of harboring class-1 integrons was rapidly reduced during serial transfers due to intI1 frameshift mutations leading to inactivated integrases. We use a mathematical model to explore the conditions where integrons with functional integrases are maintained and conclude that environmental fluctuations and episodic selection is necessary for the maintenance of functional integrases. Taken together, the presented data suggest a trade-off between the ability to capture gene cassettes and long-term stability of integrons and provide an explanation for the frequent observation of inactive integron-integrases in bacterial populations.
Zdroje
1. ThomasCM, NielsenKM (2005) Mechanisms of, and barriers to, horizontal gene transfer between bacteria. Nature Rev Microbiol 3: 711–721.
2. OchmanH, LawrenceJG, GroismanEA (2000) Lateral gene transfer and the nature of bacterial innovation. Nature 405: 299–304.
3. BergOG, KurlandCG (2002) Evolution of microbial genomes: sequence acquisition and loss. Molecular biology and evolution 19: 2265–2276.
4. BoumaJE, LenskiRE (1988) Evolution of a bacteria/plasmid association. Nature 335: 351–352.
5. DahlbergC, ChaoL (2003) Amelioration of the cost of conjugative plasmid carriage in Eschericha coli K12. Genetics 165: 1641–1649.
6. LindPA, TobinC, BergOG, KurlandCG, AnderssonDI (2010) Compensatory gene amplification restores fitness after inter-species gene replacements. Mol Microbiol 75: 1078–1089.
7. LevinBR, LipsitchM, PerrotV, SchragS, AntiaR, et al. (1997) The population genetics of antibiotic resistance. Clin Infect Dis 24 Suppl 1: S9–16.
8. JohnsenPJ, SimonsenGS, OlsvikO, MidtvedtT, SundsfjordA (2002) Stability, persistence, and evolution of plasmid-encoded VanA glycopeptide resistance in enterococci in the absence of antibiotic selection in vitro and in gnotobiotic mice. Microb Drug Resist 8: 161–170.
9. SandegrenL, LinkeviciusM, LytsyB, MelhusA, AnderssonDI (2012) Transfer of an Escherichia coli ST131 multiresistance cassette has created a Klebsiella pneumoniae-specific plasmid associated with a major nosocomial outbreak. J Antimicrob Chemother 67: 74–83.
10. AnderssonDI, HughesD (2010) Antibiotic resistance and its cost: is it possible to reverse resistance? Nature Rev Microbiol 8: 260–271.
11. JohnsenPJ, TownsendJP, BohnT, SimonsenGS, SundsfjordA, et al. (2009) Factors affecting the reversal of antimicrobial-drug resistance. Lancet Infect Dis 9: 357–364.
12. RayJL, HarmsK, WikmarkOG, StarikovaI, JohnsenPJ, et al. (2009) Sexual isolation in Acinetobacter baylyi is locus-specific and varies 10,000-fold over the genome. Genetics 182: 1165–1181.
13. EnneVI, DelsolAA, DavisGR, HaywardSL, RoeJM, et al. (2005) Assessment of the fitness impacts on Escherichia coli of acquisition of antibiotic resistance genes encoded by different types of genetic element. J Antimicrob Chemother 56: 544–551.
14. ElenaSF, LenskiRE (1997) Test of synergistic interactions among deleterious mutations in bacteria. Nature 390: 395–398.
15. FoucaultML, DepardieuF, CourvalinP, Grillot-CourvalinC (2010) Inducible expression eliminates the fitness cost of vancomycin resistance in enterococci. Proc Nat Acad Sci USA 107: 16964–16969.
16. BoucherY, LabbateM, KoenigJE, StokesHW (2007) Integrons: mobilizable platforms that promote genetic diversity in bacteria. Trends Microbiol 15: 301–309.
17. JoveT, Da ReS, DenisF, MazelD, PloyMC (2010) Inverse correlation between promoter strength and excision activity in class 1 integrons. PLoS Genetics 6: e1000793.
18. WeiQ, JiangX, LiM, ChenX, LiG, et al. (2011) Transcription of integron-harboured gene cassette impacts integration efficiency in class 1 integron. Mol Microbiol 80: 1326–1336.
19. GuerinE, JoveT, TabesseA, MazelD, PloyMC (2011) High-level gene cassette transcription prevents integrase expression in class 1 integrons. J Bacteriol 193: 5675–5682.
20. MazelD (2006) Integrons: agents of bacterial evolution. Nature Rev Microbiol 4: 608–620.
21. CornagliaG, GiamarellouH, RossoliniGM (2011) Metallo-beta-lactamases: a last frontier for beta-lactams? Lancet Infect Dis 11: 381–393.
22. BetteridgeT, PartridgeSR, IredellJR, StokesHW (2011) Genetic context and structural diversity of class 1 integrons from human commensal bacteria in a hospital intensive care unit. Antimicrob Agents Chemother 55: 3939–3943.
23. LiebertCA, HallRM, SummersAO (1999) Transposon Tn21, flagship of the floating genome. Microbiology and molecular biology reviews: MMBR 63: 507–522.
24. StokesHW, HallRM (1989) A novel family of potentially mobile DNA elements encoding site-specific gene-integration functions: integrons. Mol Microbiol 3: 1669–1683.
25. Leverstein-van HallMA, BoxAT, BlokHE, PaauwA, FluitAC, et al. (2002) Evidence of extensive interspecies transfer of integron-mediated antimicrobial resistance genes among multidrug-resistant Enterobacteriaceae in a clinical setting. J Infect Dis 186: 49–56.
26. RosewarneCP, PettigroveV, StokesHW, ParsonsYM (2010) Class 1 integrons in benthic bacterial communities: abundance, association with Tn402-like transposition modules and evidence for coselection with heavy-metal resistance. FEMS Microbiol Ecol 72: 35–46.
27. CambrayG, GueroutAM, MazelD (2010) Integrons. Ann Rev Genetics 44: 141–166.
28. NemergutDR, RobesonMS, KyselaRF, MartinAP, SchmidtSK, et al. (2008) Insights and inferences about integron evolution from genomic data. BMC Genomics 9: 261.
29. GuerinE, CambrayG, Sanchez-AlberolaN, CampoyS, ErillI, et al. (2009) The SOS response controls integron recombination. Science 324: 1034.
30. GillingsMR, HolleyMP, StokesHW, HolmesAJ (2005) Integrons in Xanthomonas: a source of species genome diversity. Proc Nat Acad Sci USA 102: 4419–4424.
31. JohnsenPJ, DubnauD, LevinBR (2009) Episodic selection and the maintenance of competence and natural transformation in Bacillus subtilis. Genetics 181: 1521–1533.
32. BarbeV, VallenetD, FonknechtenN, KreimeyerA, OztasS, et al. (2004) Unique features revealed by the genome sequence of Acinetobacter sp. ADP1, a versatile and naturally transformation competent bacterium. Nucleic Acids Res 32: 5766–5779.
33. BjorkmanJ, NagaevI, BergOG, HughesD, AnderssonDI (2000) Effects of environment on compensatory mutations to ameliorate costs of antibiotic resistance. Science 287: 1479–1482.
34. Maisnier-PatinS, BergOG, LiljasL, AnderssonDI (2002) Compensatory adaptation to the deleterious effect of antibiotic resistance in Salmonella typhimurium. Mol Microbiol 46: 355–366.
35. RozenDE, McGeeL, LevinBR, KlugmanKP (2007) Fitness costs of fluoroquinolone resistance in Streptococcus pneumoniae. Antimicrob Agents Chemother 51: 412–416.
36. ReynoldsMG (2000) Compensatory evolution in rifampin-resistant Escherichia coli. Genetics 156: 1471–1481.
37. CambrayG, Sanchez-AlberolaN, CampoyS, GuerinE, Da ReS, et al. (2011) Prevalence of SOS-mediated control of integron integrase expression as an adaptive trait of chromosomal and mobile integrons. Mob DNA 2: 6.
38. HareJ, BradleyJ, LinCL, ElamT (2011) Diverse DNA damage responses in Acinetobacter include the capacity for DNA damage-induced mutagenesis in the opportunistic pathogens Acinetobacter baumannii and Acinetobacter ursingii. Microbiology 158(Pt 3) 601–11.
39. RobinsonA, BrzoskaAJ, TurnerKM, WithersR, HarryEJ, et al. (2010) Essential biological processes of an emerging pathogen: DNA replication, transcription, and cell division in Acinetobacter spp. Microbiology and molecular biology reviews: MMBR 74: 273–297.
40. RecchiaGD, StokesHW, HallRM (1994) Characterisation of specific and secondary recombination sites recognised by the integron DNA integrase. Nucleic Acids Res 22: 2071–2078.
41. DuboisV, DebreyerC, LitvakS, QuentinC, ParissiV (2007) A new in vitro strand transfer assay for monitoring bacterial class 1 integron recombinase IntI1 activity. PloS One 2: e1315.
42. DuboisV, DebreyerC, QuentinC, ParissiV (2009) In vitro recombination catalyzed by bacterial class 1 integron integrase IntI1 involves cooperative binding and specific oligomeric intermediates. PloS One 4: e5228.
43. JuniE (1974) Simple genetic transformation assay for rapid diagnosis of Moraxella osloensis. Appl Microbiol 27: 16–24.
44. KicksteinE, HarmsK, WackernagelW (2007) Deletions of recBCD or recD influence genetic transformation differently and are lethal together with a recJ deletion in Acinetobacter baylyi. Microbiology 153: 2259–2270.
45. DedonderR (1966) Levansucrose from Bacillus subtilis. Methods Enzymol 8: 500–505.
46. HarmsK, de VriesJ, WackernagelW (2007) A double kill gene cassette for the positive selection of transforming non-selective DNA segments in Acinetobacter baylyi BD413. J Microbiol Met 69: 107–115.
47. LenskiRE, RoseMR, SimpsonSC, TadlerSC (1991) Long-term experimental evolution in Escherichia coli. 1. Adaptation and divergence during 2,000 generations. Am Nat 138: 1315–1341.
48. HarmsK, SchonV, KicksteinE, WackernagelW (2007) The RecJ DNase strongly suppresses genomic integration of short but not long foreign DNA fragments by homology-facilitated illegitimate recombination during transformation of Acinetobacter baylyi. Mol Microbiol 64: 691–702.
49. RegoesRR, WiuffC, ZappalaRM, GarnerKN, BaqueroF, et al. (2004) Pharmacodynamic functions: a multiparameter approach to the design of antibiotic treatment regimens. Antimicrob Agents Chemother 48: 3670–3676.
50. LevinBR, UdekwuKI (2010) Population dynamics of antibiotic treatment: a mathematical model and hypotheses for time-kill and continuous-culture experiments. Antimicrob Agents Chemother 54: 3414–3426.
51. UdekwuKI, ParrishN, AnkomahP, BaqueroF, LevinBR (2009) Functional relationship between bacterial cell density and the efficacy of antibiotics. J Antimicrob Chemother 63: 745–757.
52. StewartFM, LevinBR (1973) Resource partitioning and the outcome of interspecific competition: a model and some general considerations. Amer Nat 107: 171–198.
53. R Development Core Team (2011) R: A language and environment for statistical computing. 2.14.1 ed. Vienna, Austria: R Foundation for Statistical Computing.
54. SoetaertK, PetzoldtT, SetzerRW (2010) Solving differential equations in R: Package deSolve. J Stat Software 33: 1–25.
55. DominguesS, HarmsK, FrickeFW, JohnsenPJ, da SilvaGJ, et al. (2012) Natural transformation facilitates transfer of transposons, integrons and gene cassettes between bacterial species. PLoS Pathogens 8: e1002837.
56. KarahN, HaldorsenB, HermansenNO, TvetenY, RagnhildstveitE, et al. (2011) Emergence of OXA-carbapenemase- and 16S rRNA methylase-producing international clones of Acinetobacter baumannii in Norway. J Med Microbiol 60: 515–521.
57. CornejoOE, RozenDE, MayRM, LevinBR (2009) Oscillations in continuous culture populations of Streptococcus pneumoniae: population dynamics and the evolution of clonal suicide. Proc R Soc B 276: 999–1008.
58. BacherJM, MetzgarD, de Crecy-LagardV (2006) Rapid evolution of diminished transformability in Acinetobacter baylyi. J Bacteriol 188: 8534–8542.
59. StokesHW, O'GormanDB, RecchiaGD, ParsekhianM, HallRM (1997) Structure and function of 59-base element recombination sites associated with mobile gene cassettes. Mol Microbiol 26: 731–745.
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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