title: The cyclic AMP (cAMP)-cAMP receptor protein signaling system mediates resistance of Vibrio cholerae O1 strains to multiple environmental bacteriophages.
abstract: Toxigenic Vibrio cholerae, the causative agent of the epidemic diarrheal disease cholera, interacts with diverse environmental bacteriophages. These interactions promote genetic diversity or cause selective enrichment of phage-resistant bacterial clones. To identify bacterial genes involved in mediating the phage-resistant phenotype, we screened a transposon insertion library of V. cholerae O1 El Tor biotype strain C6706 to identify mutants showing altered susceptibility to a panel of phages isolated from surface waters in Bangladesh. Mutants with insertion in cyaA or crp genes encoding adenylate cyclase or cyclic AMP (cAMP) receptor protein (CRP), respectively, were susceptible to a phage designated JSF9 to which the parent strain was completely resistant. Application of the cyaA mutant as an indicator strain in environmental phage monitoring enhanced phage detection, and we identified 3 additional phages to which the parent strain was resistant. Incorporation of the cyaA or crp mutations into other V. cholerae O1 strains caused similar alterations in their phage susceptibility patterns, and the susceptibility correlated with the ability of the bacteria to adsorb these phages. Our results suggest that cAMP-CRP-mediated downregulation of phage adsorption may contribute to a mechanism for the V. cholerae O1 strains to survive predation by multiple environmental phages. Furthermore, the cyaA or crp mutant strains may be used as suitable indicators in monitoring cholera phages in the water.
authors.affiliation: Molecular Genetics Laboratory, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka-1212, Bangladesh.
authors.forename: M Shamim Hasan
authors.initials: MS
authors.lastname: Zahid
authors.forename: T M Zaved
authors.initials: TM
authors.lastname: Waise
authors.forename: M
authors.initials: M
authors.lastname: Kamruzzaman
authors.forename: Amar N
authors.initials: AN
authors.lastname: Ghosh
authors.forename: G Balakrish
authors.initials: GB
authors.lastname: Nair
authors.forename: John J
authors.initials: JJ
authors.lastname: Mekalanos
authors.forename: Shah M
authors.initials: SM
authors.lastname: Faruque
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism; D001435:Bacteriophages / Q000302:isolation & purification / Q000502:physiology*; D001459:Bangladesh; D002373:Cyclic AMP Receptor Protein / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation; D009154:Mutation; D045483:Rivers / Q000821:virology*; D015398:Signal Transduction; D041241:Vibrio cholerae O1 / Q000502:physiology / Q000821:virology*
chemical_list: D002373:Cyclic AMP Receptor Protein; D000262:Adenylyl Cyclases
references.citation: Nat Rev Microbiol. 2009 Oct;7(10):693-702
references.pmid: 19756008
references.citation: Proc Natl Acad Sci U S A. 1997 Jan 7;94(1):265-70
references.pmid: 8990197
references.citation: Arch Biochem Biophys. 1976 Jul;175(1):295-302
references.pmid: 182080
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11951-6
references.pmid: 18689675
references.citation: Microbiol Mol Biol Rev. 1998 Dec;62(4):1301-14
references.pmid: 9841673
references.citation: Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4652-7
references.pmid: 16537404
references.citation: Microbiol Mol Biol Rev. 2004 Sep;68(3):560-602, table of contents
references.pmid: 15353570
references.citation: Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1702-7
references.pmid: 15653771
references.citation: Clin Microbiol Rev. 1995 Jan;8(1):48-86
references.pmid: 7704895
references.citation: DNA Cell Biol. 2008 Jul;27(7):347-55
references.pmid: 18462070
references.citation: Microbiol Sci. 1987 Jul;4(7):214-8
references.pmid: 3153614
references.citation: J Mol Biol. 2008 Oct 31;383(1):1-9
references.pmid: 18619465
references.citation: J Clin Microbiol. 1996 Jul;34(7):1843-5
references.pmid: 8784608
references.citation: J Bacteriol. 1978 Jan;133(1):149-57
references.pmid: 201606
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):6119-24
references.pmid: 15829587
references.citation: Mol Microbiol. 2002 Mar;43(6):1577-89
references.pmid: 11952906
references.citation: Infect Immun. 2008 Nov;76(11):5266-73
references.pmid: 18794293
references.citation: J Bacteriol. 2008 Oct;190(20):6646-59
references.pmid: 18708497
references.citation: Proc Natl Acad Sci U S A. 1971 Sep;68(9):2258-62
references.pmid: 4332251
references.citation: Infect Immun. 2006 Jun;74(6):3633-42
references.pmid: 16714595
references.citation: Science. 1996 Jun 28;272(5270):1910-4
references.pmid: 8658163
references.citation: J Bacteriol. 1978 Apr;134(1):356-8
references.pmid: 206537
references.citation: Science. 2005 Dec 16;310(5755):1824-7
references.pmid: 16357262
references.citation: FEMS Microbiol Lett. 2004 Mar 12;232(1):1-6
references.pmid: 15061140
references.citation: Proc Natl Acad Sci U S A. 2008 Jun 24;105(25):8736-41
references.pmid: 18574146