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Molecular microbiology
09, 2018;109 (6): 745-762.

The lytic transglycosylase MltB connects membrane homeostasis and in vivo fitness of Acinetobacter baumannii.

Sébastien Crépin, Elizabeth N Ottosen, Katharina Peters, Sara N Smith, Stephanie D Himpsl, Waldemar Vollmer, Harry L T Mobley
Author Information
  1. Sébastien Crépin: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
  2. Elizabeth N Ottosen: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
  3. Katharina Peters: Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, UK.
  4. Sara N Smith: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
  5. Stephanie D Himpsl: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
  6. Waldemar Vollmer: Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, UK.
  7. Harry L T Mobley: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
PMID: 29884996 DOI: 10.1111/mmi.14000

Abstract

Acinetobacter baumannii has emerged as a leading nosocomial pathogen, infecting a wide range of anatomic sites including the respiratory tract and the bloodstream. In addition to being multi-drug resistant, little is known about the molecular basis of A. baumannii pathogenesis. To better understand A. baumannii virulence, a combination of a transposon-sequencing (TraDIS) screen and the neutropenic mouse model of bacteremia was used to identify the full set of fitness genes required during bloodstream infection. The lytic transglycosylase MltB was identified as a critical fitness factor. MltB cleaves the MurNAc-GlcNAc bond of peptidoglycan, which leads to cell wall remodeling. Here we show that MltB is part of a complex network connecting resistance to stresses, membrane homeostasis, biogenesis of pili and in vivo fitness. Indeed, inactivation of mltB not only impaired resistance to serum complement, cationic antimicrobial peptides and oxygen species, but also altered the cell envelope integrity, activated the envelope stress response, drastically reduced the number of pili at the cell surface and finally, significantly decreased colonization of both the bloodstream and the respiratory tract.

References

  1. Nature. 2017 Feb 28;543(7643):15 [PMID: 28252092]
  2. J Bacteriol. 2011 Jul;193(13):3367-75 [PMID: 21515766]
  3. J Bacteriol. 2016 Jun 13;198(13):1847-56 [PMID: 27114466]
  4. Int J Biochem Cell Biol. 2008;40(4):586-91 [PMID: 17468031]
  5. Infect Immun. 2010 May;78(5):1952-62 [PMID: 20194595]
  6. MBio. 2010 Nov 23;1(5):null [PMID: 21116344]
  7. J Bacteriol. 2017 Jul 25;199(16): [PMID: 28559296]
  8. mSphere. 2015 Nov 04;1(1):null [PMID: 27303682]
  9. Genome Announc. 2017 Aug 31;5(35):null [PMID: 28860239]
  10. J Am Chem Soc. 2013 Mar 6;135(9):3311-4 [PMID: 23421439]
  11. Annu Rev Biochem. 2006;75:39-68 [PMID: 16756484]
  12. J Exp Med. 1994 Jan 1;179(1):259-68 [PMID: 8270870]
  13. Microbes Infect. 2016 Sep;18(9):559-64 [PMID: 27235198]
  14. Antimicrob Agents Chemother. 2016 Apr 22;60(5):3236-9 [PMID: 26976867]
  15. MBio. 2015 Jun 09;6(3):e00775 [PMID: 26060277]
  16. Virulence. 2016 May 18;7(4):443-55 [PMID: 26854744]
  17. MBio. 2013 Jul 09;4(4):null [PMID: 23839218]
  18. Medicine (Baltimore). 1995 Nov;74(6):340-9 [PMID: 7500897]
  19. Infect Immun. 2010 Sep;78(9):3993-4000 [PMID: 20643860]
  20. Methods. 2001 Dec;25(4):402-8 [PMID: 11846609]
  21. Infect Immun. 2007 Dec;75(12):5597-608 [PMID: 17908807]
  22. Infect Immun. 2012 Mar;80(3):1015-24 [PMID: 22232188]
  23. MBio. 2017 May 23;8(3): [PMID: 28536292]
  24. J Bacteriol. 1975 Dec;124(3):1067-76 [PMID: 357]
  25. EMBO Rep. 2017 Jan;18(1):138-149 [PMID: 27920034]
  26. Cell Mol Life Sci. 2003 Nov;60(11):2371-88 [PMID: 14625683]
  27. J Bacteriol. 2015 Feb;197(3):603-14 [PMID: 25422305]
  28. Curr Protoc Microbiol. 2014 Nov 03;35:6G.2.1-11 [PMID: 25367274]
  29. MBio. 2014 Jun 03;5(3):e01163-14 [PMID: 24895306]
  30. PLoS Pathog. 2015 Feb 13;11(2):e1004691 [PMID: 25679516]
  31. PLoS Pathog. 2013;9(12):e1003788 [PMID: 24339777]
  32. Proc Natl Acad Sci U S A. 2000 May 23;97(11):5978-83 [PMID: 10811905]
  33. MBio. 2014 Aug 05;5(4):e01313-14 [PMID: 25096877]
  34. Mol Microbiol. 2003 Jul;49(2):331-45 [PMID: 12828633]
  35. MBio. 2017 May 23;8(3): [PMID: 28536290]
  36. J Bacteriol. 2007 Aug;189(15):5421-8 [PMID: 17526702]
  37. J Appl Microbiol. 2012 Jun;112(6):1075-85 [PMID: 22443589]
  38. J Biol Chem. 2017 Jun 2;292(22):9075-9087 [PMID: 28373284]
  39. PLoS Pathog. 2012;8(12):e1003068 [PMID: 23236280]
  40. MBio. 2016 Oct 11;7(5): [PMID: 27729508]
  41. Antimicrob Agents Chemother. 2006 Dec;50(12):4114-23 [PMID: 17000742]
  42. Proc Natl Acad Sci U S A. 2016 Oct 11;113(41):E6228-E6237 [PMID: 27681618]
  43. Trends Biochem Sci. 2017 Mar;42(3):232-242 [PMID: 27839654]
  44. Infect Immun. 1992 Jun;60(6):2529-35 [PMID: 1587619]
  45. PLoS Pathog. 2017 Jun 14;13(6):e1006434 [PMID: 28614382]
  46. Anal Biochem. 1988 Aug 1;172(2):451-64 [PMID: 3056100]
  47. Crit Rev Biochem Mol Biol. 2017 Oct;52(5):503-542 [PMID: 28644060]
  48. Infect Immun. 1991 Dec;59(12):4310-7 [PMID: 1937792]
  49. Clin Microbiol Rev. 2017 Jan;30(1):409-447 [PMID: 27974412]
  50. Gene. 1992 Oct 12;120(1):89-92 [PMID: 1398128]
  51. J Infect Dis. 2017 Feb 15;215(suppl_1):S9-S17 [PMID: 28375515]
  52. Nat Methods. 2012 Jun 28;9(7):676-82 [PMID: 22743772]
  53. Nat Rev Drug Discov. 2013 Dec;12(12):963 [PMID: 24232373]
  54. Microbiologyopen. 2015 Dec;4(6):879-95 [PMID: 26374494]
  55. Nat Rev Microbiol. 2011 Dec 28;10(2):123-36 [PMID: 22203377]
  56. Genome Biol. 2009;10(3):R25 [PMID: 19261174]
  57. Clin Infect Dis. 1996 Sep;23(3):538-42 [PMID: 8879777]
  58. Infect Immun. 2012 Aug;80(8):2802-15 [PMID: 22665376]
  59. Proc Natl Acad Sci U S A. 2009 Jun 2;106(22):8824-9 [PMID: 19458048]
  60. BMC Microbiol. 2010 Nov 09;10:279 [PMID: 21062436]
  61. Nat Protoc. 2011 Nov 17;6(12):1969-80 [PMID: 22094732]
  62. J Bacteriol. 2015 Dec 14;198(4):711-9 [PMID: 26668261]
  63. PLoS Pathog. 2016 Jan 14;12(1):e1005391 [PMID: 26764912]
  64. Philos Trans R Soc Lond B Biol Sci. 2015 Jun 5;370(1670):20140082 [PMID: 25918440]
  65. Genome Res. 2009 Dec;19(12):2308-16 [PMID: 19826075]
  66. Clin Infect Dis. 2004 Aug 1;39(3):309-17 [PMID: 15306996]
  67. Trends Microbiol. 2016 May;24(5):377-390 [PMID: 27068053]
  68. Vet Res. 2017 Apr 4;48(1):17 [PMID: 28376905]
  69. Antimicrob Agents Chemother. 2017 Aug 24;61(9): [PMID: 28674047]
  70. Crit Care Med. 2003 Oct;31(10):2478-82 [PMID: 14530754]
  71. Infect Immun. 2005 Jul;73(7):4138-45 [PMID: 15972503]
  72. MBio. 2015 Nov 10;6(6):e01660-15 [PMID: 26556274]
  73. ACS Infect Dis. 2017 Sep 8;3(9):624-633 [PMID: 28585815]
  74. J Bacteriol. 2007 Oct;189(20):7335-42 [PMID: 17704217]
  75. J Bacteriol. 2002 Nov;184(22):6093-9 [PMID: 12399477]
  76. Infect Immun. 2017 Jan 26;85(2): [PMID: 27895129]
  77. J Biol Chem. 2012 Mar 30;287(14):11222-33 [PMID: 22334697]
  78. J Bacteriol. 2014 Jul;196(14):2616-26 [PMID: 24816603]
  79. Mol Microbiol. 2014 Jul;93(1):113-28 [PMID: 24806796]
  80. EcoSal Plus. 2009 Aug;3(2):null [PMID: 26443759]
  81. Cell Microbiol. 2017 Mar;19(3): [PMID: 27597434]

Grants

  1. /Wellcome Trust
  2. R21 AI107184/NIAID NIH HHS
  3. 101824/Z/13/Z/Wellcome Trust

MeSH Term

Acinetobacter Infections
Acinetobacter baumannii
Animals
Antimicrobial Cationic Peptides
Cell Membrane
Complement System Proteins
Female
Glycosyltransferases
High-Throughput Nucleotide Sequencing
Mice
Mice, Inbred CBA
Muramic Acids
Peptidoglycan
Stress, Physiological

Chemicals

Antimicrobial Cationic Peptides
Muramic Acids
Peptidoglycan
N-acetylmuramic acid
Complement System Proteins
Glycosyltransferases
murein transglycosylase
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
Article has an altmetric score of 9

Word Cloud

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