Emergence of Antibiotic Resistance from Multinucleated Bacterial Filaments

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2014 Dec 11

PMID 25492931

Citations 95

Authors

Julia Bos

Qiucen Zhang

Saurabh Vyawahare

Elizabeth Rogers

Susan M Rosenberg

Robert H Austin

Affiliations

Soon will be listed here.

Abstract

Bacteria can rapidly evolve resistance to antibiotics via the SOS response, a state of high-activity DNA repair and mutagenesis. We explore here the first steps of this evolution in the bacterium Escherichia coli. Induction of the SOS response by the genotoxic antibiotic ciprofloxacin changes the E. coli rod shape into multichromosome-containing filaments. We show that at subminimal inhibitory concentrations of ciprofloxacin the bacterial filament divides asymmetrically repeatedly at the tip. Chromosome-containing buds are made that, if resistant, propagate nonfilamenting progeny with enhanced resistance to ciprofloxacin as the parent filament dies. We propose that the multinucleated filament creates an environmental niche where evolution can proceed via generation of improved mutant chromosomes due to the mutagenic SOS response and possible recombination of the new alleles between chromosomes. Our data provide a better understanding of the processes underlying the origin of resistance at the single-cell level and suggest an analogous role to the eukaryotic aneuploidy condition in cancer.

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References

Justice S, Hunstad D, Cegelski L, Hultgren S . Morphological plasticity as a bacterial survival strategy. Nat Rev Microbiol. 2007; 6(2):162-8. DOI: 10.1038/nrmicro1820. View

Selmecki A, Dulmage K, Cowen L, Anderson J, Berman J . Acquisition of aneuploidy provides increased fitness during the evolution of antifungal drug resistance. PLoS Genet. 2009; 5(10):e1000705. PMC: 2760147. DOI: 10.1371/journal.pgen.1000705. View

ZOBELL C, Cobet A . FILAMENT FORMATION BY ESCHERICHIA COLI AT INCREASED HYDROSTATIC PRESSURES. J Bacteriol. 1964; 87:710-9. PMC: 277075. DOI: 10.1128/jb.87.3.710-719.1964. View

Al Mamun A, Lombardo M, Shee C, Lisewski A, Gonzalez C, Lin D . Identity and function of a large gene network underlying mutagenic repair of DNA breaks. Science. 2012; 338(6112):1344-8. PMC: 3782309. DOI: 10.1126/science.1226683. View

Strathern J, Shafer B, McGill C . DNA synthesis errors associated with double-strand-break repair. Genetics. 1995; 140(3):965-72. PMC: 1206680. DOI: 10.1093/genetics/140.3.965. View

ROSENBERG S, Longerich S, Gee P, Harris R . Adaptive mutation by deletions in small mononucleotide repeats. Science. 1994; 265(5170):405-7. DOI: 10.1126/science.8023163. View

Di Noia J, Neuberger M . Molecular mechanisms of antibody somatic hypermutation. Annu Rev Biochem. 2007; 76:1-22. DOI: 10.1146/annurev.biochem.76.061705.090740. View

Rajagopalan H, Nowak M, Vogelstein B, Lengauer C . The significance of unstable chromosomes in colorectal cancer. Nat Rev Cancer. 2003; 3(9):695-701. DOI: 10.1038/nrc1165. View

Roberts S, Sterling J, Thompson C, Harris S, Mav D, Shah R . Clustered mutations in yeast and in human cancers can arise from damaged long single-strand DNA regions. Mol Cell. 2012; 46(4):424-35. PMC: 3361558. DOI: 10.1016/j.molcel.2012.03.030. View

10.

Duesberg P, Stindl R, Hehlmann R . Explaining the high mutation rates of cancer cells to drug and multidrug resistance by chromosome reassortments that are catalyzed by aneuploidy. Proc Natl Acad Sci U S A. 2000; 97(26):14295-300. PMC: 18912. DOI: 10.1073/pnas.97.26.14295. View

11.

Sung H, Yasbin R . Adaptive, or stationary-phase, mutagenesis, a component of bacterial differentiation in Bacillus subtilis. J Bacteriol. 2002; 184(20):5641-53. PMC: 139596. DOI: 10.1128/JB.184.20.5641-5653.2002. View

12.

Cirz R, Chin J, Andes D, de Crecy-Lagard V, Craig W, Romesberg F . Inhibition of mutation and combating the evolution of antibiotic resistance. PLoS Biol. 2005; 3(6):e176. PMC: 1088971. DOI: 10.1371/journal.pbio.0030176. View

13.

Ryan D, Monsey D . Bacterial filamentation and in vivo efficacy: a comparison of several cephalosporins. J Antimicrob Chemother. 1981; 7(1):57-63. DOI: 10.1093/jac/7.1.57. View

14.

Miller C, Thomsen L, Gaggero C, Mosseri R, Ingmer H, Cohen S . SOS response induction by beta-lactams and bacterial defense against antibiotic lethality. Science. 2004; 305(5690):1629-31. DOI: 10.1126/science.1101630. View

15.

Hadany L, Beker T . On the evolutionary advantage of fitness-associated recombination. Genetics. 2004; 165(4):2167-79. PMC: 1462912. DOI: 10.1093/genetics/165.4.2167. View

16.

Parry B, Surovtsev I, Cabeen M, OHern C, Dufresne E, Jacobs-Wagner C . The bacterial cytoplasm has glass-like properties and is fluidized by metabolic activity. Cell. 2013; 156(1-2):183-94. PMC: 3956598. DOI: 10.1016/j.cell.2013.11.028. View

17.

Harris R, Longerich S, ROSENBERG S . Recombination in adaptive mutation. Science. 1994; 264(5156):258-60. DOI: 10.1126/science.8146657. View

18.

Pine L, BOONE C . Comparative cell wall analyses of morphological forms within the genus Actinomyces. J Bacteriol. 1967; 94(4):875-83. PMC: 276748. DOI: 10.1128/jb.94.4.875-883.1967. View

19.

Stackhouse R, Faith N, Kaspar C, Czuprynski C, Lee Wong A . Survival and virulence of Salmonella enterica serovar enteritidis filaments induced by reduced water activity. Appl Environ Microbiol. 2012; 78(7):2213-20. PMC: 3302626. DOI: 10.1128/AEM.06774-11. View

20.

Justice S, Hunstad D, Seed P, Hultgren S . Filamentation by Escherichia coli subverts innate defenses during urinary tract infection. Proc Natl Acad Sci U S A. 2006; 103(52):19884-9. PMC: 1750882. DOI: 10.1073/pnas.0606329104. View