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.


Article metrics loading...

Loading full text...

Full text loading...



  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 aeruginosaJ Bacteriol 19642064215 [View Article][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 MenHJ Med Chem 4874687476 [View Article][PubMed]. [Google Scholar]
  3. Boutros M., Ahringer J. (2008). The art and design of genetic screens: RNA interferenceNat Rev Genet 9554566 [View Article][PubMed]. [Google Scholar]
  4. Chopra I. (2007). Bacterial RNA polymerase: a promising target for the discovery of new antimicrobial agentsCurr Opin Investig Drugs 8600607[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 bacteriumMol Syst Biol 7528 [View Article][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 machineryProc Natl Acad Sci U S A 1062187221877 [View Article][PubMed]. [Google Scholar]
  7. Corrigan R.M., Gründling A. (2013). Cyclic di-AMP: another second messenger enters the frayNat Rev Microbiol 11513524 [View Article][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 fibrosisPLoS One 7e50731 [View Article][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 ADP1Mol Syst Biol 4174 [View Article][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 pulmonisMol Microbiol 696776 [View Article][PubMed]. [Google Scholar]
  11. Gallagher L.A., Shendure J., Manoil C. (2011). Genome-scale identification of resistance functions in Pseudomonas aeruginosa using Tn-seqMBio 2e00315e00310 [View Article][PubMed]. [Google Scholar]
  12. Ghosal A., Nielsen P.E. (2012). Potent antibacterial antisense peptide-peptide nucleic acid conjugates against Pseudomonas aeruginosaNucleic Acid Ther 22323334[PubMed]. [Google Scholar]
  13. Goemans C., Denoncin K., Collet J.F. (2014). Folding mechanisms of periplasmic proteinsBiochim Biophys Acta 184315171528 [View Article][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 coliJ Biosci Bioeng 1165258 [View Article][PubMed]. [Google Scholar]
  15. Imlay J.A. (2013). The molecular mechanisms and physiological consequences of oxidative stress: lessons from a model bacteriumNat Rev Microbiol 11443454 [View Article][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 aeruginosaProc Natl Acad Sci U S A 1001433914344 [View Article][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 RNAScience 29322662269 [View Article][PubMed]. [Google Scholar]
  18. Juhas M. (2015a). [View Article][Epub ahead of print]. On the road to synthetic life: the minimal cell and genome-scale engineeringCrit Rev Biotechnol(Epub ahead of print). [View Article][PubMed] [Google Scholar]
  19. Juhas M. (2015b). Type IV secretion systems and genomic islands-mediated horizontal gene transfer in Pseudomonas and HaemophilusMicrobiol Res 1701017 [View Article][PubMed]. [Google Scholar]
  20. Juhas M. (2015c). Horizontal gene transfer in human pathogensCrit Rev Microbiol 41101108 [View Article][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 aeruginosaMicrobiology 150831841 [View Article][PubMed]. [Google Scholar]
  22. Juhas M., Eberl L., Tümmler B. (2005a). Quorum sensing: the power of cooperation in the world of PseudomonasEnviron Microbiol 7459471 [View Article][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 TBFEMS Microbiol Lett 242287295 [View Article][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 islandsJ Bacteriol 189761771 [View Article][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 islandsGenome Biol 8R237 [View Article][PubMed]. [Google Scholar]
  26. Juhas M., Crook D.W., Hood D.W. (2008). Type IV secretion systems: tools of bacterial horizontal gene transfer and virulenceCellular Microbiology 1023772386 [View Article][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 evolutionFEMS Microbiol Rev 33376393 [View Article][PubMed]. [Google Scholar]
  28. Juhas M., Eberl L., Glass J.I. (2011). Essence of life: essential genes of minimal genomesTrends Cell Biol 21562568 [View Article][PubMed]. [Google Scholar]
  29. Juhas M., Eberl L., Church G.M. (2012a). Essential genes as antimicrobial targets and cornerstones of synthetic biologyTrends Biotechnol 30601607 [View Article][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 cenocepaciaPLoS One 7e40064 [View Article][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 ICEHin1056Plasmid 70277283 [View Article][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 engineeringMicrobiology 16023412351 [View Article][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 bacteriaPLoS One 8e60666 [View Article][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 mutantsGenome Res 1923082316 [View Article][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 actionProc Natl Acad Sci U S A 1061457014575 [View Article][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 aeruginosaProc Natl Acad Sci U S A 11251895194 [View Article][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 mutantsProc Natl Acad Sci U S A 10328332838 [View Article][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 mechanismsClin Microbiol Rev 22582610 [View Article][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 elementsNucleic Acids Res D1D574D580 [View Article][PubMed]. [Google Scholar]
  40. Marcusson L.L., Frimodt-Møller N., Hughes D. (2009). Interplay in the selection of fluoroquinolone resistance and bacterial fitnessPLoS Pathog 5e1000541 [View Article][PubMed]. [Google Scholar]
  41. McCutcheon J.P., Moran N.A. (2010). Functional convergence in reduced genomes of bacterial symbionts spanning 200 My of evolutionGenome Biol Evol 2708718[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 growthJ Biol Chem 28820042017 [View Article][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 genesFEMS Microbiol Lett 3294553 [View Article][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 developmentMBio 5e00926e00913 [View Article][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. designFEMS Microbiol Rev 33225235 [View Article][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 exportersNature 500102106 [View Article][PubMed]. [Google Scholar]
  47. Nikaido H., Pagès J.M. (2012). Broad-specificity efflux pumps and their role in multidrug resistance of Gram-negative bacteriaFEMS Microbiol Rev 36340363 [View Article][PubMed]. [Google Scholar]
  48. Opperman T.J., Nguyen S.T. (2015). Recent advances toward a molecular mechanism of efflux pump inhibitionFront Microbiol 6421 [View Article][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 growthCell Reports 6293300 [View Article][PubMed]. [Google Scholar]
  50. Penterman J., Singh P.K., Walker G.C. (2014b). Biological cost of pyocin production during the SOS response in Pseudomonas aeruginosaJ Bacteriol 19633513359 [View Article][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 coliScience 31210441046 [View Article][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 siteScience 316, 1759-1761. [Google Scholar]
  53. Romero P., Karp P. (2003). PseudoCyc, a pathway-genome database for Pseudomonas aeruginosaJ Mol Microbiol Biotechnol 5230239 [View Article][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 aeruginosaBMC Microbiol 1424 [View Article][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 inhibitorsAntimicrob Agents Chemother 5868706878 [View Article][PubMed]. [Google Scholar]
  56. Sheppard K., Akochy P.M., Söll D. (2008). Assays for transfer RNA-dependent amino acid biosynthesisMethods 44139145 [View Article][PubMed]. [Google Scholar]
  57. Sigurdsson G., Fleming R.M., Heinken A., Thiele I. (2012). A systems biology approach to drug targets in Pseudomonas aeruginosa biofilmPLoS One 7e34337 [View Article][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 librariesPLoS Pathog 9e1003582 [View Article][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 aeruginosaScience 32710101013 [View Article][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 modelNucleic Acids Res 41687699 [View Article][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 sputumProc Natl Acad Sci U S A 11241104115 [View Article][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 mediaMBio 3e00113e00112 [View Article][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 antibioticsChemBioChem 1317671775 [View Article][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 formationJ Bacteriol 195213219 [View Article][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 aeruginosaMBio 5e01010e01013 [View Article][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 genomesNucleic Acids Res 39D596D600 [View Article][PubMed]. [Google Scholar]

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error