1887

Abstract

is the leading cause of nosocomial infections, particularly in immunocompromised, cancer, burn and cystic fibrosis patients. Development of novel antimicrobials against is therefore of the highest importance. Although the first reports on essential genes date back to the early 2000s, a number of more sensitive genomic approaches have been used recently to better define essential genes in this organism. These analyses highlight the evolution of the definition of an ‘essential’ gene from the traditional to the context-dependent. Essential genes, particularly those indispensable under the clinically relevant conditions, are considered to be promising targets of novel antibiotics against . This review provides an update on the investigation of essential genes. Special focus is on recently identified essential genes and their exploitation for the development of antimicrobials.

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2015-11-01
2019-12-16
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References

  1. Arai H., Kawakami T., Osamura T., Hirai T., Sakai Y., Ishii M.. ( 2014;). Enzymatic characterization and in vivo function of five terminal oxidases in Pseudomonas aeruginosa. J Bacteriol 196: 4206–4215 [CrossRef] [PubMed].
    [Google Scholar]
  2. Benkovic S.J., Baker S.J., Alley M.R., Woo Y.H., Zhang Y.K., Akama T., Mao W., Baboval J., Rajagopalan P.T.. & other authors ( 2005;). Identification of borinic esters as inhibitors of bacterial cell growth and bacterial methyltransferases, CcrM and MenH. J Med Chem 48: 7468–7476 [CrossRef] [PubMed].
    [Google Scholar]
  3. Boutros M., Ahringer J.. ( 2008;). The art and design of genetic screens: RNA interference. Nat Rev Genet 9: 554–566 [CrossRef] [PubMed].
    [Google Scholar]
  4. Chopra I.. ( 2007;). Bacterial RNA polymerase: a promising target for the discovery of new antimicrobial agents. Curr Opin Investig Drugs 8: 600–607 [PubMed].
    [Google Scholar]
  5. Christen B., Abeliuk E., Collier J.M., Kalogeraki V.S., Passarelli B., Coller J.A., Fero M.J., McAdams H.H., Shapiro L.. ( 2011;). The essential genome of a bacterium. Mol Syst Biol 7: 528 [CrossRef] [PubMed].
    [Google Scholar]
  6. Chung H.S., Yao Z., Goehring N.W., Kishony R., Beckwith J., Kahne D.. ( 2009;). Rapid beta-lactam-induced lysis requires successful assembly of the cell division machinery. Proc Natl Acad Sci U S A 106: 21872–21877 [CrossRef] [PubMed].
    [Google Scholar]
  7. Corrigan R.M., Gründling A.. ( 2013;). Cyclic di-AMP: another second messenger enters the fray. Nat Rev Microbiol 11: 513–524 [CrossRef] [PubMed].
    [Google Scholar]
  8. Cramer N., Wiehlmann L., Ciofu O., Tamm S., Høiby N., Tümmler B.. ( 2012;). Molecular epidemiology of chronic Pseudomonas aeruginosa airway infections in cystic fibrosis. PLoS One 7: e50731 [CrossRef] [PubMed].
    [Google Scholar]
  9. de Berardinis V., Vallenet D., Castelli V., Besnard M., Pinet A., Cruaud C., Samair S., Lechaplais C., Gyapay G., other authors. ( 2008;). A complete collection of single-gene deletion mutants of Acinetobacter baylyi ADP1. Mol Syst Biol 4: 174 [CrossRef] [PubMed].
    [Google Scholar]
  10. French C.T., Lao P., Loraine A.E., Matthews B.T., Yu H., Dybvig K.. ( 2008;). Large-scale transposon mutagenesis of Mycoplasma pulmonis. Mol Microbiol 69: 67–76 [CrossRef] [PubMed].
    [Google Scholar]
  11. Gallagher L.A., Shendure J., Manoil C.. ( 2011;). Genome-scale identification of resistance functions in Pseudomonas aeruginosa using Tn-seq. MBio 2: e00315–e00310 [CrossRef] [PubMed].
    [Google Scholar]
  12. Ghosal A., Nielsen P.E.. ( 2012;). Potent antibacterial antisense peptide-peptide nucleic acid conjugates against Pseudomonas aeruginosa. Nucleic Acid Ther 22: 323–334 [PubMed].
    [Google Scholar]
  13. Goemans C., Denoncin K., Collet J.F.. ( 2014;). Folding mechanisms of periplasmic proteins. Biochim Biophys Acta 1843: 1517–1528 [CrossRef] [PubMed].
    [Google Scholar]
  14. Hirokawa Y., Kawano H., Tanaka-Masuda K., Nakamura N., Nakagawa A., Ito M., Mori H., Oshima T., Ogasawara N.. ( 2013;). Genetic manipulations restored the growth fitness of reduced-genome Escherichia coli. J Biosci Bioeng 116: 52–58 [CrossRef] [PubMed].
    [Google Scholar]
  15. Imlay J.A.. ( 2013;). The molecular mechanisms and physiological consequences of oxidative stress: lessons from a model bacterium. Nat Rev Microbiol 11: 443–454 [CrossRef] [PubMed].
    [Google Scholar]
  16. Jacobs M.A., Alwood A., Thaipisuttikul I., Spencer D., Haugen E., Ernst S., Will O., Kaul R., Raymond C., other authors. ( 2003;). Comprehensive transposon mutant library of Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 100: 14339–14344 [CrossRef] [PubMed].
    [Google Scholar]
  17. Ji Y., Zhang B., Van Horn S.F., Warren P., Woodnutt G., Burnham M.K., Rosenberg M.. ( 2001;). Identification of critical staphylococcal genes using conditional phenotypes generated by antisense RNA. Science 293: 2266–2269 [CrossRef] [PubMed].
    [Google Scholar]
  18. Juhas M.. ( 2015a;). [CrossRef] [Epub ahead of print]. On the road to synthetic life: the minimal cell and genome-scale engineering. Crit Rev Biotechnol (Epub ahead of print). [CrossRef] [PubMed]
    [Google Scholar]
  19. Juhas M.. ( 2015b;). Type IV secretion systems and genomic islands-mediated horizontal gene transfer in Pseudomonas and Haemophilus. Microbiol Res 170: 10–17 [CrossRef] [PubMed].
    [Google Scholar]
  20. Juhas M.. ( 2015c;). Horizontal gene transfer in human pathogens. Crit Rev Microbiol 41: 101–108 [CrossRef] [PubMed].
    [Google Scholar]
  21. Juhas M., Wiehlmann L., Huber B., Jordan D., Lauber J., Salunkhe P., Limpert A.S., von Götz F., Steinmetz I., other authors. ( 2004;). Global regulation of quorum sensing and virulence by VqsR in Pseudomonas aeruginosa. Microbiology 150: 831–841 [CrossRef] [PubMed].
    [Google Scholar]
  22. Juhas M., Eberl L., Tümmler B.. ( 2005a;). Quorum sensing: the power of cooperation in the world of Pseudomonas. Environ Microbiol 7: 459–471 [CrossRef] [PubMed].
    [Google Scholar]
  23. Juhas M., Wiehlmann L., Salunkhe P., Lauber J., Buer J., Tümmler B.. ( 2005b;). GeneChip expression analysis of the VqsR regulon of Pseudomonas aeruginosa TB. FEMS Microbiol Lett 242: 287–295 [CrossRef] [PubMed].
    [Google Scholar]
  24. Juhas M., Crook D.W., Dimopoulou I.D., Lunter G., Harding R.M., Ferguson D.J.P., Hood D.W.. ( 2007a;). Novel type IV secretion system involved in propagation of genomic islands. J Bacteriol 189: 761–771 [CrossRef] [PubMed].
    [Google Scholar]
  25. Juhas M., Power P.M., Harding R.M., Ferguson D.J., Dimopoulou I.D., Elamin A.R., Mohd-Zain Z., Hood D.W., Adegbola R., other authors. ( 2007b;). Sequence and functional analyses of Haemophilus spp. genomic islands. Genome Biol 8: R237 [CrossRef] [PubMed].
    [Google Scholar]
  26. Juhas M., Crook D.W., Hood D.W.. ( 2008;). Type IV secretion systems: tools of bacterial horizontal gene transfer and virulence. Cellular Microbiology 10: 2377–2386 [CrossRef] [PubMed].
    [Google Scholar]
  27. Juhas M., van der Meer J.R., Gaillard M., Harding R.M., Hood D.W., Crook D.W.. ( 2009;). Genomic islands: tools of bacterial horizontal gene transfer and evolution. FEMS Microbiol Rev 33: 376–393 [CrossRef] [PubMed].
    [Google Scholar]
  28. Juhas M., Eberl L., Glass J.I.. ( 2011;). Essence of life: essential genes of minimal genomes. Trends Cell Biol 21: 562–568 [CrossRef] [PubMed].
    [Google Scholar]
  29. Juhas M., Eberl L., Church G.M.. ( 2012a;). Essential genes as antimicrobial targets and cornerstones of synthetic biology. Trends Biotechnol 30: 601–607 [CrossRef] [PubMed].
    [Google Scholar]
  30. Juhas M., Stark M., von Mering C., Lumjiaktase P., Crook D.W., Valvano M.A., Eberl L.. ( 2012b;). High confidence prediction of essential genes in Burkholderia cenocepacia. PLoS One 7: e40064 [CrossRef] [PubMed].
    [Google Scholar]
  31. Juhas M., Dimopoulou I., Robinson E., Elamin A., Harding R., Hood D., Crook D.. ( 2013;). Identification of another module involved in the horizontal transfer of the Haemophilus genomic island ICEHin1056. Plasmid 70: 277–283 [CrossRef] [PubMed].
    [Google Scholar]
  32. Juhas M., Reuß D.R., Zhu B., Commichau F.M.. ( 2014;). Bacillus subtilis and Escherichia coli essential genes and minimal cell factories after one decade of genome engineering. Microbiology 160: 2341–2351 [CrossRef] [PubMed].
    [Google Scholar]
  33. Lamers R.P., Cavallari J.F., Burrows L.L.. ( 2013;). The efflux inhibitor phenylalanine-arginine beta-naphthylamide (PAβN) permeabilizes the outer membrane of Gram-negative bacteria. PLoS One 8: e60666 [CrossRef] [PubMed].
    [Google Scholar]
  34. Langridge G.C., Phan M.D., Turner D.J., Perkins T.T., Parts L., Haase J., Charles I., Maskell D.J., Peters S.E., other authors. ( 2009;). Simultaneous assay of every Salmonella Typhi gene using one million transposon mutants. Genome Res 19: 2308–2316 [CrossRef] [PubMed].
    [Google Scholar]
  35. Lee S., Hinz A., Bauerle E., Angermeyer A., Juhaszova K., Kaneko Y., Singh P.K., Manoil C.. ( 2009;). Targeting a bacterial stress response to enhance antibiotic action. Proc Natl Acad Sci U S A 106: 14570–14575 [CrossRef] [PubMed].
    [Google Scholar]
  36. Lee S.A., Gallagher L.A., Thongdee M., Staudinger B.J., Lippman S., Singh P.K., Manoil C.. ( 2015;). General and condition-specific essential functions of Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 112: 5189–5194 [CrossRef] [PubMed].
    [Google Scholar]
  37. Liberati N.T., Urbach J.M., Miyata S., Lee D.G., Drenkard E., Wu G., Villanueva J., Wei T., Ausubel F.M.. ( 2006;). An ordered, nonredundant library of Pseudomonas aeruginosa strain PA14 transposon insertion mutants. Proc Natl Acad Sci U S A 103: 2833–2838 [CrossRef] [PubMed].
    [Google Scholar]
  38. Lister P.D., Wolter D.J., Hanson N.D.. ( 2009;). Antibacterial-resistant Pseudomonas aeruginosa: clinical impact and complex regulation of chromosomally encoded resistance mechanisms. Clin Microbiol Rev 22: 582–610 [CrossRef] [PubMed].
    [Google Scholar]
  39. Luo H., Lin Y., Gao F., Zhang C.T., Zhang R.. ( 2014;). DEG 10, an update of the database of essential genes that includes both protein-coding genes and noncoding genomic elements. Nucleic Acids Res D1: D574–D580 [CrossRef] [PubMed].
    [Google Scholar]
  40. Marcusson L.L., Frimodt-Møller N., Hughes D.. ( 2009;). Interplay in the selection of fluoroquinolone resistance and bacterial fitness. PLoS Pathog 5: e1000541 [CrossRef] [PubMed].
    [Google Scholar]
  41. McCutcheon J.P., Moran N.A.. ( 2010;). Functional convergence in reduced genomes of bacterial symbionts spanning 200 My of evolution. Genome Biol Evol 2: 708–718 [PubMed].
    [Google Scholar]
  42. Mehne F.M., Gunka K., Eilers H., Herzberg C., Kaever V., Stülke J.. ( 2013;). Cyclic di-AMP homeostasis in Bacillus subtilis: both lack and high level accumulation of the nucleotide are detrimental for cell growth. J Biol Chem 288: 2004–2017 [CrossRef] [PubMed].
    [Google Scholar]
  43. Meng J., Kanzaki G., Meas D., Lam C.K., Crummer H., Tain J., Xu H.H.. ( 2012;). A genome-wide inducible phenotypic screen identifies antisense RNA constructs silencing Escherichia coli essential genes. FEMS Microbiol Lett 329: 45–53 [CrossRef] [PubMed].
    [Google Scholar]
  44. Moule M.G., Hemsley C.M., Seet Q., Guerra-Assunção J.A., Lim J., Sarkar-Tyson M., Clark T.G., Tan P.B., Titball R.W., other authors. ( 2014;). Genome-wide saturation mutagenesis of Burkholderia pseudomallei K96243 predicts essential genes and novel targets for antimicrobial development. MBio 5: e00926–e00913 [CrossRef] [PubMed].
    [Google Scholar]
  45. Moya A., Gil R., Latorre A., Peretó J., Pilar Garcillán-Barcia M., de la Cruz F.. ( 2009;). Toward minimal bacterial cells: evolution vs. design. FEMS Microbiol Rev 33: 225–235 [CrossRef] [PubMed].
    [Google Scholar]
  46. Nakashima R., Sakurai K., Yamasaki S., Hayashi K., Nagata C., Hoshino K., Onodera Y., Nishino K., Yamaguchi A.. ( 2013;). Structural basis for the inhibition of bacterial multidrug exporters. Nature 500: 102–106 [CrossRef] [PubMed].
    [Google Scholar]
  47. Nikaido H., Pagès J.M.. ( 2012;). Broad-specificity efflux pumps and their role in multidrug resistance of Gram-negative bacteria. FEMS Microbiol Rev 36: 340–363 [CrossRef] [PubMed].
    [Google Scholar]
  48. Opperman T.J., Nguyen S.T.. ( 2015;). Recent advances toward a molecular mechanism of efflux pump inhibition. Front Microbiol 6: 421 [CrossRef] [PubMed].
    [Google Scholar]
  49. Penterman J., Nguyen D., Anderson E., Staudinger B.J., Greenberg E.P., Lam J.S., Singh P.K.. ( 2014a;). Rapid evolution of culture-impaired bacteria during adaptation to biofilm growth. Cell Reports 6: 293–300 [CrossRef] [PubMed].
    [Google Scholar]
  50. Penterman J., Singh P.K., Walker G.C.. ( 2014b;). Biological cost of pyocin production during the SOS response in Pseudomonas aeruginosa. J Bacteriol 196: 3351–3359 [CrossRef] [PubMed].
    [Google Scholar]
  51. Pósfai G., Plunkett G. III, Fehér T., Frisch D., Keil G.M., Umenhoffer K., Kolisnychenko V., Stahl B., Sharma S.S., other authors. ( 2006;). Emergent properties of reduced-genome Escherichia coli. Science 312: 1044–1046 [CrossRef] [PubMed].
    [Google Scholar]
  52. Rock F.L., Mao W., Yaremchuk A., Tukalo M., Crépin T., Zhou H., Zhang Y.K., Hernandez V., Akama T., other authors. ( 2007;). An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site. Science 316, 1759-1761.
    [Google Scholar]
  53. Romero P., Karp P.. ( 2003;). PseudoCyc, a pathway-genome database for Pseudomonas aeruginosa. J Mol Microbiol Biotechnol 5: 230–239 [CrossRef] [PubMed].
    [Google Scholar]
  54. Rusmini R., Vecchietti D., Macchi R., Vidal-Aroca F., Bertoni G.. ( 2014;). A shotgun antisense approach to the identification of novel essential genes in Pseudomonas aeruginosa. BMC Microbiol 14: 24 [CrossRef] [PubMed].
    [Google Scholar]
  55. Schuster S., Kohler S., Buck A., Dambacher C., König A., Bohnert J.A., Kern W.V.. ( 2014;). Random mutagenesis of the multidrug transporter AcrB from Escherichia coli for identification of putative target residues of efflux pump inhibitors. Antimicrob Agents Chemother 58: 6870–6878 [CrossRef] [PubMed].
    [Google Scholar]
  56. Sheppard K., Akochy P.M., Söll D.. ( 2008;). Assays for transfer RNA-dependent amino acid biosynthesis. Methods 44: 139–145 [CrossRef] [PubMed].
    [Google Scholar]
  57. Sigurdsson G., Fleming R.M., Heinken A., Thiele I.. ( 2012;). A systems biology approach to drug targets in Pseudomonas aeruginosa biofilm. PLoS One 7: e34337 [CrossRef] [PubMed].
    [Google Scholar]
  58. Skurnik D., Roux D., Aschard H., Cattoir V., Yoder-Himes D., Lory S., Pier G.B.. ( 2013;). A comprehensive analysis of in vitro and in vivo genetic fitness of Pseudomonas aeruginosa using high-throughput sequencing of transposon libraries. PLoS Pathog 9: e1003582 [CrossRef] [PubMed].
    [Google Scholar]
  59. Srinivas N., Jetter P., Ueberbacher B.J., Werneburg M., Zerbe K., Steinmann J., Van der Meijden B., Bernardini F., Lederer A., other authors. ( 2010;). Peptidomimetic antibiotics target outer-membrane biogenesis in Pseudomonas aeruginosa. Science 327: 1010–1013 [CrossRef] [PubMed].
    [Google Scholar]
  60. Tanaka K., Henry C.S., Zinner J.F., Jolivet E., Cohoon M.P., Xia F., Bidnenko V., Ehrlich S.D., Stevens R.L., Noirot P.. ( 2013;). Building the repertoire of dispensable chromosome regions in Bacillus subtilis entails major refinement of cognate large-scale metabolic model. Nucleic Acids Res 41: 687–699 [CrossRef] [PubMed].
    [Google Scholar]
  61. Turner K.H., Wessel A.K., Palmer G.C., Murray J.L., Whiteley M.. ( 2015;). Essential genome of Pseudomonas aeruginosa in cystic fibrosis sputum. Proc Natl Acad Sci U S A 112: 4110–4115 [CrossRef] [PubMed].
    [Google Scholar]
  62. Umland T.C., Schultz L.W., MacDonald U., Beanan J.M., Olson R., Russo T.A.. ( 2012;). In vivo-validated essential genes identified in Acinetobacter baumannii by using human ascites overlap poorly with essential genes detected on laboratory media. MBio 3: e00113–e00112 [CrossRef] [PubMed].
    [Google Scholar]
  63. Werneburg M., Zerbe K., Juhas M., Bigler L., Stalder U., Kaech A., Ziegler U., Obrecht D., Eberl L., Robinson J.A.. ( 2012;). Inhibition of lipopolysaccharide transport to the outer membrane in Pseudomonas aeruginosa by peptidomimetic antibiotics. ChemBioChem 13: 1767–1775 [CrossRef] [PubMed].
    [Google Scholar]
  64. Wessel A.K., Liew J., Kwon T., Marcotte E.M., Whiteley M.. ( 2013;). Role of Pseudomonas aeruginosa peptidoglycan-associated outer membrane proteins in vesicle formation. J Bacteriol 195: 213–219 [CrossRef] [PubMed].
    [Google Scholar]
  65. Wiens J.R., Vasil A.I., Schurr M.J., Vasil M.L.. ( 2014;). Iron-regulated expression of alginate production, mucoid phenotype, and biofilm formation by Pseudomonas aeruginosa. MBio 5: e01010–e01013 [CrossRef] [PubMed].
    [Google Scholar]
  66. Winsor G.L., Lam D.K., Fleming L., Lo R., Whiteside M.D., Yu N.Y., Hancock R.E., Brinkman F.S.. ( 2011;). Pseudomonas Genome Database: improved comparative analysis and population genomics capability for Pseudomonas genomes. Nucleic Acids Res 39: D596–D600 [CrossRef] [PubMed].
    [Google Scholar]
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