title: Bis-(3'-5')-cyclic dimeric GMP regulates antimicrobial peptide resistance in Pseudomonas aeruginosa.
abstract: Bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) is an intracellular second messenger that controls the lifestyles of many bacteria. A high intracellular level of c-di-GMP induces a biofilm lifestyle, whereas a low intracellular level of c-di-GMP stimulates dispersal of biofilms and promotes a planktonic lifestyle. Here, we used the expression of different reporters to show that planktonic cells, biofilm cells, and cells dispersed from biofilms (DCells) had distinct intracellular c-di-GMP levels. Proteomics analysis showed that the low intracellular c-di-GMP level of DCells induced the expression of proteins required for the virulence and development of antimicrobial peptide resistance in Pseudomonas aeruginosa. In accordance with this, P. aeruginosa cells with low c-di-GMP levels were found to be more resistant to colistin than P. aeruginosa cells with high c-di-GMP levels. This finding contradicts the current dogma stating that dispersed cells are inevitably more susceptible to antibiotics than their sessile counterparts.
authors: Singapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, Singapore.
authors: Song Lin
authors: SL
authors: Chua
authors: Sean Yang-Yi
authors: SY
authors: Tan
authors: Morten Theil
authors: MT
authors: Rybtke
authors: Yicai
authors: Y
authors: Chen
authors: Scott A
authors: SA
authors: Rice
authors: Staffan
authors: S
authors: Kjelleberg
authors: Tim
authors: T
authors: Tolker-Nielsen
authors: Liang
authors: L
authors: Yang
authors: Michael
authors: M
authors: Givskov
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D003091:Colistin / Q000494:pharmacology*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000187:drug effects* / Q000235:genetics; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D010933:Plankton / Q000187:drug effects / Q000254:growth & development; D040901:Proteomics; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D015290:Second Messenger Systems / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D049452:Green Fluorescent Proteins; C062025:bis(3',5')-cyclic diguanylic acid; D006152:Cyclic GMP; D003091:Colistin
references: J Bacteriol. 2012 Jun;194(11):2904-15
references: 22493016
references: Antimicrob Agents Chemother. 2009 Oct;53(10):4345-51
references: 19635950
references: J Microbiol Methods. 2012 Feb;88(2):229-36
references: 22178430
references: Mol Microbiol. 2008 Jul;69(2):376-89
references: 18485075
references: Appl Environ Microbiol. 2012 Aug;78(15):5060-9
references: 22582064
references: Gene. 1994 Oct 11;148(1):81-6
references: 7926843
references: Mol Microbiol. 2010 Feb;75(4):815-26
references: 19602146
references: J Biol Chem. 2005 Sep 30;280(39):33324-30
references: 16081414
references: FEMS Immunol Med Microbiol. 2012 Jul;65(2):366-76
references: 22309122
references: Environ Microbiol. 2011 Jul;13(7):1705-17
references: 21605307
references: J Bacteriol. 2007 Jul;189(14):5383-6
references: 17496081
references: Mol Microbiol. 2005 Jun;56(5):1234-45
references: 15882417
references: Gene. 1999 Feb 18;227(2):197-203
references: 10023058
references: Appl Environ Microbiol. 2008 Jul;74(13):4199-209
references: 18487410
references: Wound Repair Regen. 2011 May-Jun;19(3):387-91
references: 21518086
references: Mol Microbiol. 2004 Aug;53(3):857-69
references: 15255898
references: Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2839-44
references: 16477007
references: Mol Microbiol. 1998 Oct;30(2):295-304
references: 9791175
references: J Biol Chem. 2007 Feb 2;282(5):2987-95
references: 17148441
references: Annu Rev Microbiol. 1995;49:711-45
references: 8561477
references: Contrib Microbiol. 2009;16:136-149
references: 19494583
references: Mol Microbiol. 2005 Aug;57(3):629-39
references: 16045609
references: J Bacteriol. 1951 Sep;62(3):293-300
references: 14888646
references: J Bacteriol. 2004 Jan;186(2):575-9
references: 14702327
references: Mol Microbiol. 2009 Dec;74(6):1380-92
references: 19889094
references: Proc Natl Acad Sci U S A. 2007 May 29;104(22):9469-74
references: 17517597
references: Microbiology (Reading). 2009 Nov;155(Pt 11):3500-3508
references: 19643762
references: J Bacteriol. 2007 Jan;189(1):28-37
references: 17041046
references: Microbiology (Reading). 2000 Oct;146 ( Pt 10):2543-2554
references: 11021929
references: Mol Microbiol. 2003 Oct;50(1):205-17
references: 14507375
references: Pediatr Pulmonol. 2009 Jun;44(6):547-58
references: 19418571
references: Annu Rev Microbiol. 1986;40:79-105
references: 3535656
references: Nat Rev Microbiol. 2008 Mar;6(3):199-210
references: 18264116
references: FEMS Immunol Med Microbiol. 2012 Jul;65(2):146-57
references: 22066868
references: Gene. 1995 Dec 1;166(1):175-6
references: 8529885
references: Nat Rev Microbiol. 2009 Apr;7(4):263-73
references: 19287449
references: Mol Microbiol. 2010 Feb;75(4):827-42
references: 20088866
references: Mol Gen Genet. 1992 May;233(1-2):293-301
references: 1318499
references: Rev Infect Dis. 1983 Mar-Apr;5(2):279-313
references: 6405475
references: Antimicrob Agents Chemother. 2010 Sep;54(9):3960-3
references: 20566773
references: Nat Rev Immunol. 2003 Sep;3(9):710-20
references: 12949495
references: Mol Microbiol. 2006 Feb;59(4):1114-28
references: 16430688
references: J Microbiol Methods. 2001 Jul;45(3):187-95
references: 11348676