Advertisement

Antibacterial New Target Discovery: Sentinel Examples, Strategies, and Surveying Success

  • Holly A. Sutterlin
  • Juliana C. Malinverni
  • Sang Ho Lee
  • Carl J. Balibar
  • Terry Roemer
Chapter
Part of the Topics in Medicinal Chemistry book series (TMC, volume 25)

Abstract

Antibiotics are the bedrock of modern medicine but their efficacy is rapidly eroding due to the alarming emergence of multi-drug resistant bacteria. To begin to address this crisis, novel antibacterial agents that inhibit bacterial-specific cellular functions essential for growth, viability, and/or pathogenesis are urgently needed. Although the genomics era has contributed greatly to identifying novel antibacterial targets, it has failed to appropriately characterize, prioritize, and ultimately exploit such targets to significantly impact antibiotic discovery. Here we describe a contemporary view of new antibacterial target discovery; one which complements existing genomics strategies with a deeply rooted and fundamental understanding of target biology in the context of genetic networks and environmental conditions to rigorously identify high potential targets, and cognate inhibitors, for consideration as antibacterial leads.

Keywords

Antibiotic Antibiotic resistance Conditional essential Drug target Outer membrane biogenesis Synthetic lethality Wall teichoic acid 

References

  1. 1.
    Piddock L (2012) The crisis of no new antibiotics – what is the way forward? Lancet Infect Dis 12(3):249–253. doi: 10.1016/S1473-3099(11)70316-4CrossRefPubMedGoogle Scholar
  2. 2.
    Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D, Rice LB, Scheld M, Spellberg B, Bartlett J (2009) Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis 48:1–12. doi: 10.1086/595011CrossRefPubMedGoogle Scholar
  3. 3.
    Brown ED, Wright GD (2016) Antibacterial drug discovery in the resistance era. Nature 529(7586):336–343. doi: 10.1038/nature17042CrossRefGoogle Scholar
  4. 4.
    Ventola CL (2015) The antibiotic resistance crisis: part 1: causes and threats. P T 40(4):277–283PubMedPubMedCentralGoogle Scholar
  5. 5.
    Woolhouse M, Ward M, van Bunnik B, Farrar J (2015) Antimicrobial resistance in humans, livestock and the wider environment. Philos Trans R Soc B Biol Sci 370(1670):20140083. doi: 10.1098/rstb.2014.0083CrossRefGoogle Scholar
  6. 6.
    Kinch MS, Patridge E, Plummer M, Hoyer D (2014) An analysis of FDA-approved drugs for infectious disease: antibacterial agents. Drug Discov Today 19(9):1283–1287. doi: 10.1016/j.drudis.2014.07.005CrossRefPubMedGoogle Scholar
  7. 7.
    Walsh C, Wencewicz T (2016) Antibiotics: challenges, mechanisms, opportunities. ASM Press, Washington, DCGoogle Scholar
  8. 8.
    Butler MS, Blaskovich MA, Cooper MA (2015) Antibiotics in the clinical pipeline at the end of 2015. J Antibiot (Tokyo). DOI:  10.1038/ja.2016.72CrossRefPubMedGoogle Scholar
  9. 9.
    Klahn P, Brönstrup M (2016) New structural templates for clinically validated and novel targets in antimicrobial drug research and development. Curr Top Microbiol Immunol. DOI:  10.1007/82_2016_501CrossRefGoogle Scholar
  10. 10.
    Gerdes SY, Scholle MD, Campbell JW, Balázsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D’Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabási AL, Oltvai ZN, Osterman AL (2003) Experimental determination and system level analysis of essential genes in Escherichia coli MG1655. J Bacteriol 185(19):5673–5684. doi: 10.1128/JB.185.19.5673-5684.2003CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006) Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection. Mol Syst Biol 2:2006.0008. doi: 10.1038/msb4100050CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Winzeler EA, Shoemaker DD, Astromoff A, Liang H, Anderson K, Andre B, Bangham R, Benito R, Boeke JD, Bussey H, Chu AM, Connelly C, Davis K, Dietrich F, Dow SW, El Bakkoury M, Foury F, Friend SH, Gentalen E, Giaever G, Hegemann JH, Jones T, Laub M, Liao H, Liebundguth N, Lockhart DJ, Lucau-Danila A, Lussier M, M’Rabet N, Menard P, Mittmann M, Pai C, Rebischung C, Revuelta JL, Riles L, Roberts CJ, Ross-MacDonald P, Scherens B, Snyder M, Sookhai-Mahadeo S, Storms RK, Véronneau S, Voet M, Volckaert G, Ward TR, Wysocki R, Yen GS, Zimmermann K, Philippsen P, Johnston M, Davis RW (1999) Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285(5429):901–906. doi: 10.1126/science.285.5429.901CrossRefPubMedGoogle Scholar
  13. 13.
    Giaever G, Chu AM, Ni L, Connelly C, Riles L, Véronneau S, Dow S, Lucau-Danila A, Anderson K, André B, Arkin AP, Astromoff A, El-Bakkoury M, Bangham R, Benito R, Brachat S, Campanaro S, Curtiss M, Davis K, Deutschbauer A, Entian KD, Flaherty P, Foury F, Garfinkel DJ, Gerstein M, Gotte D, Güldener U, Hegemann JH, Hempel S, Herman Z, Jaramillo DF, Kelly DE, Kelly SL, Kötter P, LaBonte D, Lamb DC, Lan N, Liang H, Liao H, Liu L, Luo C, Lussier M, Mao R, Menard P, Ooi SL, Revuelta JL, Roberts CJ, Rose M, Ross-Macdonald P, Scherens B, Schimmack G, Shafer B, Shoemaker DD, Sookhai-Mahadeo S, Storms RK, Strathern JN, Valle G, Voet M, Volckaert G, Wang CY, Ward TR, Wilhelmy J, Winzeler EA, Yang Y, Yen G, Youngman E, Yu K, Bussey H, Boeke JD, Snyder M, Philippsen P, Davis RW, Johnston M (2002) Functional profiling of the Saccharomyces cerevisiae genome. Nature 418(6896):387–391. doi: 10.1038/nature00935CrossRefPubMedGoogle Scholar
  14. 14.
    Roemer T, Jiang B, Davison J, Ketela T, Veillette K, Breton A, Tandia F, Linteau A, Sillaots S, Marta C, Martel N, Veronneau S, Lemieux S, Kauffman S, Becker J, Storms R, Boone C, Bussey H (2003) Large-scale essential gene identification in Candida albicans and applications to antifungal drug discovery. Mol Microbiol 50(1):167–181. doi: 10.1046/j.1365-2958.2003.03697.xCrossRefPubMedGoogle Scholar
  15. 15.
    Payne DJ, Gwynn MN, Holmes DJ, Pompliano DL (2007) Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat Rev Drug Discov 6(1):29–40. doi: 10.1038/nrd2201CrossRefGoogle Scholar
  16. 16.
    Tommasi R, Brown DG, Walkup GK, Manchester JI, Miller AA (2015) ESKAPEing the labyrinth of antibacterial discovery. Nat Rev Drug Discov 14(8):529–542. doi: 10.1038/nrd4572CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Lewis K (2012) Antibiotics: recover the lost art of drug discovery. Nature 485(7399):439–440. doi: 10.1038/485439aCrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Baltz RH (2006) Marcel Faber roundtable: is our antibiotic pipeline unproductive because of starvation, constipation or lack of inspiration? J Ind Microbiol Biotechnol 33(7):507–513. doi: 10.1007/s10295-005-0077-9CrossRefPubMedGoogle Scholar
  19. 19.
    O’Shea R, Moser HE (2008) Physicochemical properties of antibacterial compounds: implications for drug discovery. J Med Chem 51(10):2871–2878. doi: 10.1021/jm700967eCrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Brown DG, May-Dracka TL, Gagnon MM, Tommasi R (2014) Trends and exceptions of physical properties on antibacterial activity for Gram-positive and Gram-negative pathogens. J Med Chem 57(23):10144–10161. doi: 10.1021/jm501552xCrossRefGoogle Scholar
  21. 21.
    Projan SJ (2008) Whither antibacterial drug discovery? Drug Discov Today 13(7–8):279–280. doi: 10.1016/j.drudis.2008.03.010CrossRefPubMedGoogle Scholar
  22. 22.
    Srinivas N, Jetter P, Ueberbacher BJ, Werneburg M, Zerbe K, Steinmann J, Van der Meijden B, Bernardini F, Lederer A, Dias RL, Misson PE, Henze H, Zumbrunn J, Gombert FO, Obrecht D, Hunziker P, Schauer S, Ziegler U, Käch A, Eberl L, Riedel K, DeMarco SJ, Robinson JA (2010) Peptidomimetic antibiotics target outer-membrane biogenesis in Pseudomonas aeruginosa. Science 327(5968):1010–1013. doi: 10.1126/science.1182749CrossRefPubMedGoogle Scholar
  23. 23.
    Hagan CL, Wzorek JS, Kahne D (2015) Inhibition of the β-barrel assembly machine by a peptide that binds BamD. Proc Natl Acad Sci U S A 112(7):2011–2016. doi: 10.1073/pnas.1415955112CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Richter SG, Elli D, Kim HK, Hendrickx AP, Sorg JA, Schneewind O, Missiakas D (2013) Small molecule inhibitor of lipoteichoic acid synthesis is an antibiotic for Gram-positive bacteria. Proc Natl Acad Sci U S A 110(9):3531–3536. doi: 10.1073/pnas.1217337110CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Nayar AS, Dougherty TJ, Ferguson KE, Granger BA, McWilliams L, Stacey C, Leach LJ, Narita S, Tokuda H, Miller AA, Brown DG, McLeod SM (2015) Novel antibacterial targets and compounds revealed by a high-throughput cell wall reporter assay. J Bacteriol 197(10):1726–1734. doi: 10.1128/JB.02552-14CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    McLeod SM, Fleming PR, MacCormack K, McLaughlin RE, Whiteaker JD, Narita S, Mori M, Tokuda H, Miller AA (2015) Small-molecule inhibitors of gram-negative lipoprotein trafficking discovered by phenotypic screening. J Bacteriol 197(6):1075–1082. doi: 10.1128/JB.02352-14CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Campbell J, Singh AK, Santa Maria Jr JP, Kim Y, Brown S, Swoboda JG, Mylonakis E, Wilkinson BJ, Walker S (2011) Synthetic lethal compound combinations reveal a fundamental connection between wall teichoic acid and peptidoglycan biosyntheses in Staphylococcus aureus. ACS Chem Biol 6(1):106–116. doi: 10.1021/cb100269fCrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Mann PA, Müller A, Xiao L, Pereira PM, Yang C, Ho Lee S, Wang H, Trzeciak J, Schneeweis J, Dos Santos MM, Murgolo N, She X, Gill C, Balibar CJ, Labroli M, Su J, Flattery A, Sherborne B, Maier R, Tan CM, Black T, Onder K, Kargman S, Monsma Jr FJ, Pinho MG, Schneider T, Roemer T (2013) Murgocil is a highly bioactive staphylococcal-specific inhibitor of the peptidoglycan glycosyltransferase enzyme MurG. ACS Chem Biol 8(11):2442–2451. doi: 10.1021/cb400487fCrossRefGoogle Scholar
  29. 29.
    Huber J, Donald RG, Lee SH, Jarantow LW, Salvatore MJ, Meng X, Painter R, Onishi RH, Occi J, Dorso K, Young K, Park YW, Skwish S, Szymonifka MJ, Waddell TS, Miesel L, Phillips JW, Roemer T (2009) Chemical genetic identification of peptidoglycan inhibitors potentiating carbapenem activity against methicillin-resistant Staphylococcus aureus. Chem Biol 16(8):837–848. doi: 10.1016/j.chembiol.2009.05.012CrossRefPubMedGoogle Scholar
  30. 30.
    Mott JE, Shaw BA, Smith JF, Bonin PD, Romero DL, Marotti KR, Miller AA (2008) Resistance mapping and mode of action of a novel class of antibacterial anthranilic acids: evidence for disruption of cell wall biosynthesis. J Antimicrob Chemother 62(4):720–729. doi: 10.1093/jac/dkn261CrossRefPubMedGoogle Scholar
  31. 31.
    Bouley R, Kumarasiri M, Peng Z, Otero LH, Song W, Suckow MA, Schroeder VA, Wolter WR, Lastochkin E, Antunes NT, Pi H, Vakulenko S, Hermoso JA, Chang M, Mobashery S (2015) Discovery of antibiotic (E)-3-(3-Carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one. J Am Chem Soc 137(5):1738–1741. doi: 10.1021/jacs.5b00056CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Lee SH, Wang H, Labroli M, Koseoglu S, Zuck P, Mayhood T, Gill C, Mann P, Sher X, Ha S, Yang SW, Mandal M, Yang C, Liang L, Tan Z, Tawa P, Hou Y, Kuvelkar R, DeVito K, Wen X, Xiao J, Batchlett M, Balibar CJ, Liu J, Xiao J, Murgolo N, Garlisi CG, Sheth PR, Flattery A, Su J, Tan C, Roemer T (2016) TarO-specific inhibitors of wall teichoic acid biosynthesis restore β-lactam efficacy against methicillin-resistant staphylococci. Sci Transl Med 8(329):329ra32. DOI:  10.1126/scitranslmed.aad7364.CrossRefPubMedGoogle Scholar
  33. 33.
    Swoboda JG, Meredith TC, Campbell J, Brown S, Suzuki T, Bollenbach T, Malhowski AJ, Kishony R, Gilmore MS, Walker S (2009) Discovery of a small molecule that blocks wall teichoic acid biosynthesis in Staphylococcus aureus. ACS Chem Biol 4(10):875–883. doi: 10.1021/cb900151kCrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Wang H, Gill CJ, Lee SH, Mann P, Zuck P, Meredith TC, Murgolo N, She X, Kales S, Liang L, Liu J, Wu J, Santa Maria J, Su J, Pan J, Hailey J, Mcguinness D, Tan CM, Flattery A, Walker S, Black T, Roemer T (2013) Discovery of wall teichoic acid inhibitors as potential anti-MRSA β-lactam combination agents. Chem Biol 20(2):272–284. doi: 10.1016/j.chembiol.2012.11.013CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Ling LL, Schneider T, Peoples AJ, Spoering AL, Engels I, Conlon BP, Mueller A, Schäberle TF, Hughes DE, Epstein S, Jones M, Lazarides L, Steadman VA, Cohen DR, Felix CR, Fetterman KA, Millett WP, Nitti AG, Zullo AM, Chen C, Lewis K (2015) A new antibiotic kills pathogens without detectable resistance. Nature 517(7535):455–459. doi: 10.1038/nature14098CrossRefPubMedGoogle Scholar
  36. 36.
    Lehar SM, Pillow T, Xu M, Staben L, Kajihara KK, Vandlen R, DePalatis L, Raab H, Hazenbos WL, Morisaki JH, Kim J, Park S, Darwish M, Lee BC, Hernandez H, Loyet KM, Lupardus P, Fong R, Yan D, Chalouni C, Luis E, Khalfin Y, Plise E, Cheong J, Lyssikatos JP, Strandh M, Koefoed K, Andersen PS, Flygare JA, Wah Tan M, Brown EJ, Mariathasan S (2015) Novel antibody-antibiotic conjugate eliminates intracellular S. aureus. Nature 527(7578):323–328. doi: 10.1038/nature16057CrossRefPubMedGoogle Scholar
  37. 37.
    Tokunaga M, Loranger JM, Wu HC (1983) Isolation and characterization of an Escherichia coli clone overproducing prolipoprotein signal peptidase. J Biol Chem 258(20):12102–12105PubMedGoogle Scholar
  38. 38.
    Dev IK, Harvey RJ, Ray PH (1985) Inhibition of prolipoprotein signal peptidase by globomycin. J Biol Chem 260(10):5891–5894PubMedGoogle Scholar
  39. 39.
    Xiao Y, Gerth K, Müller R, Wall D (2012) Myxobacterium-produced antibiotic TA (myxovirescin) inhibits type II signal peptidase. Antimicrob Agents Chemother 56(4):2014–2021. doi: 10.1128/AAC.06148-11CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Vogeley L, El Arnaout T, Bailey J, Stansfeld PJ, Boland C, Caffrey M (2016) Structural basis of lipoprotein signal peptidase II action and inhibition by the antibiotic globomycin. Science 351(6275):876–880. doi: 10.1126/science.aad3747CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    de Jonge BL, Walkup GK, Lahiri SD, Huynh H, Neckermann G, Utley L, Nash TJ, Brock J, San Martin M, Kutschke A, Johnstone M, Laganas V, Hajec L, Gu RF, Ni H, Chen B, Hutchings K, Holt E, McKinney D, Gao N, Livchak S, Thresher J (2013) Discovery of inhibitors of 4′-phosphopantetheine adenylyltransferase (PPAT) to validate PPAT as a target for antibacterial therapy. Antimicrob Agents Chemother 57(12):6005–6015. DOI:  10.1128/AAC.01661-13CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Conlon BP, Nakayasu ES, Fleck LE, LaFleur MD, Isabella VM, Coleman K, Leonard SN, Smith RD, Adkins JN, Lewis K (2013) Activated ClpP kills persisters and eradicates a chronic biofilm infection. Nature 503(7476):365–370. doi: 10.1038/nature12790CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Brötz-Oesterhelt H, Beyer D, Kroll HP, Endermann R, Ladel C, Schroeder W, Hinzen B, Raddatz S, Paulsen H, Henninger K, Bandow JE, Sahl HG, Labischinski H (2005) Dysregulation of bacterial proteolytic machinery by a new class of antibiotics. Nat Med 11(10):1082–1087. doi: 10.1038/nm1306CrossRefPubMedGoogle Scholar
  44. 44.
    Tomašić T, Šink R, Zidar N, Fic A, Contreras-Martel C, Dessen A, Patin D, Blanot D, Müller-Premru M, Gobec S, Zega A, Kikelj D, Peterlin Mašič L (2012) Dual inhibitor of MurD and MurE ligases from Escherichia coli and Staphylococcus aureus. ACS Med Chem Lett 3(8):626–630. doi: 10.1021/ml300047hCrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Pasquina L, Santa Maria Jr JP, McKay Wood B, Moussa SH, Matano LM, Santiago M, Martin SE, Lee W, Meredith TC, Walker S (2016) A synthetic lethal approach for compound and target identification in Staphylococcus aureus. Nat Chem Biol 12(1):40–45. doi: 10.1038/nchembio.1967CrossRefPubMedGoogle Scholar
  46. 46.
    Haydon DJ, Stokes NR, Ure R, Galbraith G, Bennett JM, Brown DR, Baker PJ, Barynin VV, Rice DW, Sedelnikova SE, Heal JR, Sheridan JM, Aiwale ST, Chauhan PK, Srivastava A, Taneja A, Collins I, Errington J, Czaplewski LG (2008) An inhibitor of FtsZ with potent and selective anti-staphylococcal activity. Science 321(5896):1673–1675. doi: 10.1126/science.1159961CrossRefGoogle Scholar
  47. 47.
    Tan CM, Therien AG, Lu J, Lee SH, Caron A, Gill CJ, Lebeau-Jacob C, Benton-Perdomo L, Elsen N, Wu J, Deschamps K, Petcu M, Wong S, Daigneault E, Kramer S, Liang L, Maxwell E, Claveau D, Vaillencourt J, Skorey K, Tam J, Wang H, Meredith TC, Sillaots S, Wang-Jarantow L, Reid JC, Parthasarathy G, Sharma S, Baryshnikova A, Lumb KJ, Soisson SM, Roemer T (2012) Restoring methicillin-resistant Staphylococcus aureus susceptibility to β-lactam antibiotics. Sci Transl Med 4(126):126ra35. doi: 10.1126/scitranslmed.3003592CrossRefPubMedGoogle Scholar
  48. 48.
    Mann PA, Müller A, Wolff KA, Fischmann T, Wang H, Reed P, Hou Y, Li W, Müller CE, Xiao J, Murgolo N, Sher X, Mayhood T, Sheth PR, Mirza A, Labroli M, Xiao L, McCoy M, Gill CJ, Pinho MG, Schneider T, Roemer T (2016) Chemical genetic analysis and functional characterization of staphylococcal wall teichoic acid 2-epimerases reveals unconventional antibiotic drug targets. PLoS Pathog 12(5):e1005585. doi: 10.1371/journal.ppat.1005585CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Zhu W, Zhang Y, Sinko W, Hensler ME, Olson J, Molohon KJ, Lindert S, Cao R, Li K, Wang K, Wang Y, Liu YL, Sankovsky A, de Oliveira CA, Mitchell DA, Nizet V, McCammon JA, Oldfield E (2013) Antibacterial drug leads targeting isoprenoid biosynthesis. Proc Natl Acad Sci U S A 110(1):123–128. doi: 10.1073/pnas.1219899110CrossRefPubMedGoogle Scholar
  50. 50.
    Farha MA, Czarny TL, Myers CL, Worrall LJ, French S, Conrady DG, Wang Y, Oldfield E, Strynadka NC, Brown ED (2015) Antagonism screen for inhibitors of bacterial cell wall biogenesis uncovers an inhibitor of undecaprenyl diphosphate synthase. Proc Natl Acad Sci U S A 112(35):11048–11053. doi: 10.1073/pnas.1511751112CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Czarny TL, Brown ED (2016) A small-molecule screening platform for the discovery of inhibitors of undecaprenyl diphosphate synthase. ACS Infect Dis 2(7):489–499. doi: 10.1021/acsinfecdis.6b00044CrossRefGoogle Scholar
  52. 52.
    Howe JA, Wang H, Fischmann TO, Balibar CJ, Xiao L, Galgoci AM, Malinverni JC, Mayhood T, Villafania A, Nahvi A, Murgolo N, Barbieri CM, Mann PA, Carr D, Xia E, Zuck P, Riley D, Painter RE, Walker SS, Sherborne B, de Jesus R, Pan W, Plotkin MA, Wu J, Rindgen D, Cummings J, Garlisi CG, Zhang R, Sheth PR, Gill CJ, Tang H, Roemer T (2015) Selective small-molecule inhibition of an RNA structural element. Nature 526(7575):672–677. doi: 10.1038/nature15542CrossRefPubMedGoogle Scholar
  53. 53.
    Howe JA, Xiao L, Fischmann TO, Wang H, Tang H, Villafania A, Zhang R, Barbieri CM, Roemer T (2016) Atomic resolution mechanistic studies of ribocil: a highly selective unnatural ligand mimic of the E. coli FMN riboswitch. RNA Biol 13(10):946–954. doi: 10.1080/15476286.2016.1216304CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Roemer T, Boone C (2013) Systems-level antimicrobial drug and drug synergy discovery. Nat Chem Biol 9(4):222–231. doi: 10.1038/nchembio.1205CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Hillenmeyer ME, Fung E, WildenhainJ PSE, Hoon S, Lee W, Proctor M, St Onge RP, Tyers M, Koller D, Altman RB, Davis RW, Nislow C, Giaever G (2008) The chemical genomic portrait of yeast: uncovering a phenotype for all genes. Science 320(5874):362–365. doi: 10.1126/science.1150021CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Zlitni S, Ferruccio LF, Brown ED (2013) Metabolic suppression identifies new antibacterial inhibitors under nutrient limitation. Nat Chem Biol 9(12):796–804. doi: 10.1038/nchembio.1361CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Yao J, Rock CO (2015) How bacterial pathogens eat host lipids: implications for the development of fatty acid synthesis therapeutics. J Biol Chem 290(10):5940–5946. doi: 10.1074/jbc.R114.636241CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Gründling A, Schneewind O (2007) Synthesis of glycerol phosphate lipoteichoic acid in Staphylococcus aureus. Proc Natl Acad Sci U S A 104(20):8478–8483. doi: 10.1073/pnas.0701821104CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Oku Y, Kurokawa K, Matsuo M, Yamada S, Lee BL, Sekimizu K (2009) Pleiotropic roles of polyglycerolphosphate synthase of lipoteichoic acid in growth of Staphylococcus aureus cells. J Bacteriol 191(1):141–151. doi: 10.1128/JB.01221-08CrossRefPubMedGoogle Scholar
  60. 60.
    Beckmann I, Subbaiah TV, Stocker BAD (1964) Rough mutants of Salmonella typhimurium. II. Serological and chemical investigations. Nature 201:1299–1301CrossRefGoogle Scholar
  61. 61.
    Nelson BW, Roantree RJ (1967) Analyses of lipopolysaccharides extracted from penicillin-resistant, serum-sensitive Salmonella mutants. J Gen Microbiol 48(2):179–188. doi: 10.1099/00221287-48-2-179CrossRefPubMedGoogle Scholar
  62. 62.
    Joiner KA, Schmetz MA, Sanders ME, Murray TG, Hammer CH, Dourmashkin R, Frank MM (1985) Multimeric complement component C9 is necessary for killing of Escherichia coli J5 by terminal attack complex C5b-9. Proc Natl Acad Sci U S A 82(14):4808–4812CrossRefGoogle Scholar
  63. 63.
    Schiller NL (1988) Characterization of the susceptibility of Pseudomonas aeruginosa to complement-mediated killing: role of antibodies to the rough lipopolysaccharide on serum-sensitive strains. Infect Immun 56(3):632–639PubMedPubMedCentralGoogle Scholar
  64. 64.
    Schiller NL, Joiner KA (1986) Interaction of complement with serum-sensitive and serum-resistant strains of Pseudomonas aeruginosa. Infect Immun 54(3):689–694PubMedPubMedCentralGoogle Scholar
  65. 65.
    Greenfield LK, Whitfield C (2012) Synthesis of lipopolysaccharide O-antigens by ABC transporter-dependent pathways. Carbohydr Res 356:12–24. doi: 10.1016/j.carres.2012.02.027CrossRefPubMedGoogle Scholar
  66. 66.
    Phan MD, Peters KM, Sarkar S, Lukowski SW, Allsopp LP, Gomes Moriel D, Achard ME, Totsika M, Marshall VM, Upton M, Beatson SA, Schembri MA (2013) The serum resistome of a globally disseminated multidrug resistant uropathogenic Escherichia coli clone. PLoS Genet 9(10):e1003834. doi: 10.1371/journal.pgen.1003834CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Sarkar S, Ulett GC, Totsika M, Phan MD, Schembri MA (2014) Role of capsule and O-antigen in the virulence of uropathogenic Escherichia coli. PLoS One 9(4):e94786. doi: 10.1371/journal.pone.0094786CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Dixon SJ, Costanzo M, Baryshnikova A, Andrews B, Boone C (2009) Systematic mapping of genetic interaction networks. Annu Rev Genet 43:601–625. doi: 10.1146/annurev.genet.39.073003.114751CrossRefPubMedGoogle Scholar
  69. 69.
    Tong AH, Evangelista M, Parsons AB, Xu H, Bader GD, Pagé N, Robinson M, Raghibizadeh S, Hogue CW, Bussey H, Andrews B, Tyers M, Boone C (2001) Systematic genetic analysis with ordered arrays of yeast deletion mutants. Science 294(5550):2364–2368. doi: 10.1126/science.1065810CrossRefPubMedGoogle Scholar
  70. 70.
    Costanzo M, Baryshnikova A, Bellay J, Kim Y, Spear ED, Sevier CS, Ding H, Koh JL, Toufighi K, Mostafavi S, Prinz J, St Onge RP, VanderSluis B, Makhnevych T, Vizeacoumar FJ, Alizadeh S, Bahr S, Brost RL, Chen Y, Cokol M, Deshpande R, Li Z, Lin ZY, Liang W, Marback M, Paw J, San Luis BJ, Shuteriqi E, Tong AH, van Dyk N, Wallace IM, Whitney JA, Weirauch MT, Zhong G, Zhu H, Houry WA, Brudno M, Ragibizadeh S, Papp B, Pál C, Roth FP, Giaever G, Nislow C, Troyanskaya OG, Bussey H, Bader GD, Gingras AC, Morris QD, Kim PM, Kaiser CA, Myers CL, Andrews BJ, Boone C (2010) The genetic landscape of the cell. Science 327(5964):425–431. doi: 10.1126/science.1180823CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Paradis-Bleau C, Markovski M, Uehara T, Lupoli TJ, Walker S, Kahne DE, Bernhardt TG (2010) Lipoprotein cofactors located in the outer membrane activate bacterial cell wall polymerases. Cell 143(7):1110–1120. doi: 10.1016/j.cell.2010.11.037CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Babu M, Díaz-Mejía JJ, Vlasblom J, Gagarinova A, Phanse S, Graham C, Yousif F, Ding H, Xiong X, Nazarians-Armavil A, Alamgir M, Ali M, Pogoutse O, Pe’er A, Arnold R, Michaut M, Parkinson J, Golshani A, Whitfield C, Wodak SJ, Moreno-Hagelsieb G, Greenblatt JF, Emili A (2011) Genetic interaction maps in Escherichia coli reveal functional crosstalk among cell envelope biogenesis pathways. PLoS Genet 7(11):e1002377. doi: 10.1371/journal.pgen.1002377CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Typas A, Nichols RJ, Siegele DA, Shales M, Collins SR, Lim B, Braberg H, Yamamoto N, Takeuchi R, Wanner BL, Mori H, Weissman JS, Krogan NJ, Gross CA (2008) High-throughput, quantitative analyses of genetic interactions in E. coli. Nat Methods 5(9):781–787CrossRefGoogle Scholar
  74. 74.
    Peters JM, Colavin A, Shi H, Czarny TL, Larson MH, Wong S, Hawkins JS, Lu CH, Koo BM, Marta E, Shiver AL, Whitehead EH, Weissman JS, Brown ED, Qi LS, Huang KC, Gross CA (2016) A comprehensive, CRISPR-based functional analysis of essential genes in bacteria. Cell 165(6):1493–1506. doi: 10.1016/j.cell.2016.05.003CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Roemer T, Schneider T, Pinho MG (2013) Auxiliary factors: a chink in the armor of MRSA resistance to β-lactam antibiotics. Curr Opin Microbiol 16(5):538–548. doi: 10.1016/j.mib.2013.06.012CrossRefPubMedGoogle Scholar
  76. 76.
    Lee SH, Jarantow-Wang L, Sillaots S, Cheng H, Meredith TC, Thompson J, Roemer T (2011) Antagonism of chemical genetic interaction networks resensitize MRSA to β-lactam antibiotics. Chem Biol 18(11):1379–1389. doi: 10.1016/j.chembiol.2011.08.015CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Forsyth RA, Haselbeck RJ, Ohlsen KL, Yamamoto RT, Xu H, Trawick JD, Wall D, Wang L, Brown-Driver V, Froelich JM, C KG, King P, McCarthy M, Malone C, Misiner B, Robbins D, Tan Z, Zhu Zy ZY, Carr G, Mosca DA, Zamudio C, Foulkes JG, Zyskind JW (2002) A genome-wide strategy for the identification of essential genes in Staphylococcus aureus. Mol Microbiol 43(6):1387–1400. doi: 10.1046/j.1365-2958.2002.02832.xCrossRefPubMedGoogle Scholar
  78. 78.
    Xu HH, Trawick JD, Haselbeck RJ, Forsyth RA, Yamamoto RT, Archer R, Patterson J, Allen M, Froelich JM, Taylor I, Nakaji D, Maile R, Kedar GC, Pilcher M, Brown-Driver V, McCarthy M, Files A, Robbins D, King P, Sillaots S, Malone C, Zamudio CS, Roemer T, Wang L, Youngman PJ, Wall D (2010) Staphylococcus aureus TargetArray: comprehensive differential essential gene expression as a mechanistic tool to profile antibacterials. Antimicrob Agents Chemother 54(9):3659–3670. doi: 10.1128/AAC.00308-10CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Münch D, Roemer T, Lee SH, Engeser M, Sahl HG, Schneider T (2012) Identification and in vitro analysis of the GatD/MurT enzyme-complex catalyzing lipid II amidation in Staphylococcus aureus. PLoS Pathog 8(1):e1002509. doi: 10.1371/journal.ppat.1002509CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Drawz SM, Bonomo RA (2010) Three decades of β-lactamase inhibitors. Clin Microbiol Rev 23(1):160–201. doi: 10.1128/CMR.00037-09CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    D’Elia MA, Pereira MP, Chung YS, Zhao W, Chau A, Kenney TJ, Sulavik MC, Black TA, Brown ED (2006) Lesions in teichoic acid biosynthesis in Staphylococcus aureus lead to a lethal gain of function in the otherwise dispensable pathway. J Bacteriol 188:4183–4189. doi: 10.1128/JB.00197-06CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    D’Elia MA, Millar KE, Beveridge TJ, Brown ED (2006) Wall teichoic acid polymers are dispensable for cell viability in Bacillus subtilis. J Bacteriol 188:8313–8316. doi: 10.1128/JB.01336-06CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Sewell EW, Brown ED (2014) Taking aim at wall teichoic acid synthesis: new biology and new leads for antibiotics. J Antibiot (Tokyo) 67(1):43–51. doi: 10.1038/ja.2013.100CrossRefGoogle Scholar
  84. 84.
    Pasquina LW, Santa Maria JP, Walker S (2013) Teichoic acid biosynthesis as an antibiotic target. Curr Opin Microbiol 16(5):531–537. doi: 10.1016/j.mib.2013.06.014CrossRefPubMedGoogle Scholar
  85. 85.
    Schirner K, Stone LK, Walker S (2011) ABC transporters required for export of wall teichoic acids do not discriminate between different main chain polymers. ACS Chem Biol 6(5):407–412. doi: 10.1021/cb100390wCrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Cordes EH (2014) Hallelujah moments: tales of drug discovery (chapter 9). Oxford University Press, New YorkGoogle Scholar
  87. 87.
    Bigger JW (1944) Treatment of staphylococcal infections with penicillin. Lancet 244:497–500CrossRefGoogle Scholar
  88. 88.
    Keren I, Kaldalu N, Spoering A, Wang Y, Lewis K (2004) Persister cells and tolerance to antimicrobials. FEMS Microbiol Lett 230(1):13–18. doi: 10.1016/S0378-1097(03)00856-5CrossRefPubMedGoogle Scholar
  89. 89.
    Lewis K (2010) Persister cells. Annu Rev Microbiol 64:357–372. doi: 10.1146/annurev.micro.112408.134306CrossRefPubMedGoogle Scholar
  90. 90.
    Sass P, Josten M, Famulla K, Schiffer G, Sahl HG, Hamoen L, Brötz-Oesterhelt H (2011) Antibiotic acyldepsipeptides activate ClpP peptidase to degrade the cell division protein FtsZ. Proc Natl Acad Sci U S A 108(42):17474–17479. doi: 10.1073/pnas.1110385108CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Wu T, McCandlish AC, Gronenberg LS, Chng SS, Silhavy TJ, Kahne D (2006) Identification of a protein complex that assembles lipopolysaccharide in the outer membrane of Escherichia coli. Proc Natl Acad Sci U S A 103(31):11754–11759. DOI:  10.1073/pnas.0604744103CrossRefGoogle Scholar
  92. 92.
    Koehn FE, Carter GT (2005) Rediscovering natural products as a source of new drugs. Discov Med 5(26):159–164PubMedGoogle Scholar
  93. 93.
    Schneider T, Kruse T, Wimmer R, Wiedemann I, Sass V, Pag U, Jansen A, Nielsen AK, Mygind PH, Raventós DS, Neve S, Ravn B, Bonvin AM, De Maria L, Andersen AS, Gammelgaard LK, Sahl HG, Kristensen HH (2010) Plectasin, a fungal defensin, targets the bacterial cell wall precursor Lipid II. Science 328(5982):1168–1172. doi: 10.1126/science.1185723CrossRefPubMedGoogle Scholar
  94. 94.
    Chu J, Vila-Farres X, Inoyama D, Ternei M, Cohen LJ, Gordon EA, Reddy BV, Charlop-Powers Z, Zebroski HA, Gallardo-Macias R, Jaskowski M, Satish S, Park S, Perlin DS, Freundlich JS, Brady SF (2016) Discovery of MRSA active antibiotics using primary sequence from the human microbiome. Nat Chem Biol 12:1004–1006. doi: 10.1038/nchembio.2207CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Silhavy TJ, Kahne D, Walker S (2010) The bacterial cell envelope. Cold Spring Harb Perspect Biol 2(5):a000414. doi: 10.1101/cshperspect.a000414CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Bakelar J, Buchanan SK, Noinaj N (2016) The structure of the β-barrel assembly machinery complex. Science 351(6269):180–186. doi: 10.1126/science.aad3460CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Noinaj N, Kuszak AJ, Gumbart JC, Lukacik P, Chang H, Easley NC, Lithgow T, Buchanan SK (2013) Structural insight into the biogenesis of β-barrel membrane proteins. Nature 501(7467):385–390. doi: 10.1038/nature12521CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Lee J, Xue M, Wzorek JS, Wu T, Grabowicz M, Gronenberg L, Sutterlin HA, Davis RM, Ruiz N, Silhavy TJ, Kahne DE (2016) Characterization of a stalled complex on the β-barrel assembly machine. Proc Natl Acad Sci U S A 113(31):8717–8722. doi: 10.1073/pnas.1604100113CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Dong H, Xiang Q, Gu Y, Wang Z, Paterson NG, Stansfeld PJ, He C, Zhang Y, Wang W, Dong C (2014) Structural basis for outer membrane lipopolysaccharide insertion. Nature 511(7507):52–56. doi: 10.1038/nature13464CrossRefPubMedGoogle Scholar
  100. 100.
    Qiao S, Luo Q, Zhao Y, Zhang XC, Huang Y (2014) Structural basis for lipopolysaccharide insertion in the bacterial outer membrane. Nature 511(7507):108–111. doi: 10.1038/nature13484CrossRefPubMedGoogle Scholar
  101. 101.
    Freinkman E, Chng SS, Kahne D (2011) The complex that inserts lipopolysaccharide into the bacterial outer membrane forms a two-protein plug-and-barrel. Proc Natl Acad Sci U S A 108(6):2486–2491. DOI:  10.1073/pnas.1015617108CrossRefGoogle Scholar
  102. 102.
    Chimalakonda G, Ruiz N, Chng SS, Garner RA, Kahne D, Silhavy TJ (2011) Lipoprotein LptE is required for the assembly of LptD by the beta-barrel assembly machine in the outer membrane of Escherichia coli. Proc Natl Acad Sci U S A 108(6):2492–2497. doi: 10.1073/pnas.1019089108CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Silver LL (2011) Challenges of antibacterial discovery. Clin Microbiol Rev 24(1):71–109. doi: 10.1128/CMR.00030-10CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Silver LL (2016) Appropriate targets for antibacterial drugs. Cold Spring Harb Perspect Med. pii: a030239. DOI:  10.1101/cshperspect.a030239CrossRefPubMedGoogle Scholar
  105. 105.
    O'Dwyer K, Spivak AT, Ingraham K, Min S, Holmes DJ, Jakielaszek C, Rittenhouse S, Kwan AL, Livi GP, Sathe G, Thomas E, Van Horn S, Miller LA, Twynholm M, Tomayko J, Dalessandro M, Caltabiano M, Scangarella-Oman NE, Brown JR (2015) Bacterial resistance to leucyl-tRNA synthetase inhibitor GSK2251052 develops during treatment of complicated urinary tract infections. Antimicrob Agents Chemother 59(1):289–298. doi: 10.1128/AAC.03774-14CrossRefPubMedGoogle Scholar
  106. 106.
    Thulin E, Sundqvist M, Andersson DI (2015) Amdinocillin (mecillinam) resistance mutations in clinical isolates and laboratory-selected mutants of Escherichia coli. Antimicrob Agents Chemother 59(3):1718–1727. doi: 10.1128/AAC.04819-14CrossRefPubMedPubMedCentralGoogle Scholar
  107. 107.
    Sakoulas G, Okumura CY, Thienphrapa W, Olson J, Nonejuie P, Dam Q, Dhand A, Pogliano J, Yeaman MR, Hensler ME, Bayer AS, Nizet V (2014) Nafcillin enhances innate immune-mediated killing of methicillin-resistant Staphylococcus aureus. J Mol Med (Berl) 92(2):139–149. doi: 10.1007/s00109-013-1100-7CrossRefGoogle Scholar
  108. 108.
    Weidenmaier C, Peschel A (2008) Teichoic acids and related cell-wall glycopolymers in Gram-positive physiology and host interactions. Nat Rev Microbiol 6:276–287. doi: 10.1038/nrmicro1861CrossRefPubMedGoogle Scholar
  109. 109.
    Weidenmaier C, Kokai-Kun JF, Kristian SA, Chanturiya T, Kalbacher H, Gross M, Nicholson G, Neumeister B, Mond JJ, Peschel A (2004) Role of teichoic acids in Staphylococcus aureus nasal colonization, a major risk factor in nosocomial infections. Nat Med 10(3):243–245. doi: 10.1038/nm991CrossRefPubMedGoogle Scholar
  110. 110.
    Weidenmaier C, Peschel A, Xiong YQ, Kristian SA, Dietz K, Yeaman MR, Bayer AS (2005) Lack of wall teichoic acids in Staphylococcus aureus leads to reduced interactions with endothelial cells and to attenuated virulence in a rabbit model of endocarditis. J Infect Dis 191(10):1771–1777. doi: 10.1086/429692CrossRefPubMedGoogle Scholar
  111. 111.
    Alexander DC, Valvano MA (1994) Role of the rfe gene in the biosynthesis of the Escherichia coli O7-specific lipopolysaccharide and other O-specific polysaccharides containing N-acetylglucosamine. J Bacteriol 176(22):7079–7084CrossRefGoogle Scholar
  112. 112.
    Walsh SI, Craney A, Romesberg FE (2016) Not just an antibiotic target: exploring the role of type I signal peptidase in bacterial virulence. Bioorg Med Chem 24:6370–6378. doi:http://dx.doi.org/10.1016/j.bmc.2016.09.048CrossRefGoogle Scholar
  113. 113.
    Brown DG (2016) Drug discovery strategies to outer membrane targets in Gram-negative pathogens. Bioorg Med Chem. pii: S0968-0896(16)30325-X. DOI:  10.1016/j.bmc.2016.05.004CrossRefGoogle Scholar
  114. 114.
    Brown S, Santa Maria JP, Walker S (2013) Wall teichoic acids of Gram-positive bacteria. Annu Rev Microbiol 67:313–336. doi: 10.1146/annurev-micro-092412-155620CrossRefPubMedPubMedCentralGoogle Scholar
  115. 115.
    D’Elia MA, Pereira MP, Brown ED (2009) Are essential genes really essential? Trends Microbiol 17:433–438. doi: 10.1016/j.tim.2009.08.005CrossRefPubMedGoogle Scholar
  116. 116.
    O’Neil PK, Rollauer SE, Noinaj N, Buchanan SK (2015) Fitting the pieces of the β-barrel assembly machinery complex. Biochemistry 54(41):6303–6311. doi: 10.1021/acs.biochem.5b00852CrossRefPubMedPubMedCentralGoogle Scholar
  117. 117.
    Plummer AM, Fleming KG (2016) From chaperones to the membrane with a BAM! Trends Biochem Sci 41(10):872–882. doi: 10.1016/j.tibs.2016.06.005CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Simpson BW, May JM, Sherman DJ, Kahne D, Ruiz N (2015) Lipopolysaccharide transport to the cell surface: biosynthesis and extraction from the inner membrane. Philos Trans R Soc Lond B Biol Sci. 370(1679). pii: 20150029. DOI:  10.1098/rstb.2015.0029CrossRefGoogle Scholar
  119. 119.
    May JM, Sherman DJ, Simpson BW, Ruiz N, Kahne D (2015) Lipopolysaccharide transport to the cell surface: periplasmic transport and assembly into the outer membrane. Philos Trans R Soc Lond B Biol Sci. 370(1679). pii: 20150027. DOI:  10.1098/rstb.2015.0027CrossRefGoogle Scholar
  120. 120.
    Konovalova A, Silhavy TJ (2015) Outer membrane lipoprotein biogenesis: Lol is not the end. Philos Trans R Soc Lond B Biol. 370(1679) pii: 20150030. DOI:  10.1098/rstb.2015.0030CrossRefGoogle Scholar
  121. 121.
    Whitfield C, Trent MS (2014) Biosynthesis and export of bacterial lipopolysaccharides. Annu Rev Biochem 83:99–128. doi: 10.1146/annurev-biochem-060713-035600CrossRefPubMedGoogle Scholar
  122. 122.
    Typas A, Banzhaf M, Gross CA, Vollmer W (2011) From the regulation of peptidoglycan synthesis to bacterial growth and morphology. Nat Rev Microbiol 10(2):123–136. doi: 10.1038/nrmicro2677CrossRefPubMedPubMedCentralGoogle Scholar
  123. 123.
    Lovering AL, Safadi SS, Strynadka NC (2012) Structural perspective of peptidoglycan biosynthesis and assembly. Annu Rev Biochem 81:451–478. doi: 10.1146/annurev-biochem-061809-112742CrossRefPubMedGoogle Scholar
  124. 124.
    Woodward L, Naismith JH (2016) Bacterial polysaccharide synthesis and export. Curr Opin Struct Biol 40:81–88. doi: 10.1016/j.sbi.2016.07.016CrossRefPubMedGoogle Scholar
  125. 125.
    Rowley G, Spector M, Kormanec J, Roberts M (2006) Pushing the envelope: extracytoplasmic stress responses in bacterial pathogens. Nat Rev Microbiol 4(5):383–394. doi: 10.1038/nrmicro1394CrossRefPubMedGoogle Scholar
  126. 126.
    Guest RL, Raivio TL (2016) Role of the Gram-negative envelope stress response in the presence of antimicrobial agents. Trends Microbiol 24(5):377–390. doi: 10.1016/j.tim.2016.03.001CrossRefPubMedGoogle Scholar
  127. 127.
    Nikaido H (2003) Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev 67(4):593–656. doi: 10.1128/MMBR.67.4.593-656.2003CrossRefPubMedPubMedCentralGoogle Scholar
  128. 128.
    Gray AN, Egan AJ, Van't Veer IL, Verheul J, Colavin A, Koumoutsi A, Biboy J, Altelaar AF, Damen MJ, Huang KC, Simorre JP, Breukink E, den Blaauwen T, Typas A, Gross CA, Vollmer W (2015) Coordination of peptidoglycan synthesis and outer membrane constriction during Escherichia coli cell division. eLife 4. DOI:  10.7554/eLife.07118
  129. 129.
    Typas A, Banzhaf M, van den Berg van Saparoea B, Verheul J, Biboy J, Nichols RJ, Zietek M, Beilharz K, Kannenberg K, von Rechenberg M, Breukink E, den Blaauwen T, Gross CA, Vollmer W (2010) Regulation of peptidoglycan synthesis by outer-membrane proteins. Cell 143(7):1097–1109. doi: 10.1016/j.cell.2010.11.038CrossRefPubMedPubMedCentralGoogle Scholar
  130. 130.
    Rigel NW, Schwalm J, Ricci DP, Silhavy TJ (2012) BamE modulates the Escherichia coli β-barrel assembly machine component BamA. J Bacteriol 194(5):1002–1008. doi: 10.1128/JB.06426-11CrossRefPubMedPubMedCentralGoogle Scholar
  131. 131.
    Rigel NW, Ricci DP, Silhavy TJ (2013) Conformation-specific labeling of BamA and suppressor analysis suggest a cyclic mechanism for β-barrel assembly in Escherichia coli. Proc Natl Acad Sci U S A 110(13):5151–5156. doi: 10.1073/pnas.1302662110CrossRefPubMedPubMedCentralGoogle Scholar
  132. 132.
    Cuthbertson L, Powers J, Whitfield C (2005) The C-terminal domain of the nucleotide-binding domain protein Wzt determines substrate specificity in the ATP-binding cassette transporter for the lipopolysaccharide O-antigens in Escherichia coli serotypes O8 and O9a. J Biol Chem 280(34):30310–30319. doi: 10.1074/jbc.M504371200CrossRefPubMedGoogle Scholar
  133. 133.
    Silver LL (2016) A Gestalt approach to Gram-negative entry. Bioorg Med Chem 24:6379–6389. doi:http://dx.doi.org/10.1016/j.bmc.2016.06.044CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  • Holly A. Sutterlin
    • 1
  • Juliana C. Malinverni
    • 1
  • Sang Ho Lee
    • 1
  • Carl J. Balibar
    • 1
  • Terry Roemer
    • 1
  1. 1.Merck Research LaboratoriesKenilworthUSA

Personalised recommendations