title: Horizontal transfer of tetracycline resistance among Chlamydia spp. in vitro.
abstract: There are no examples of stable tetracycline resistance in clinical strains of Chlamydia trachomatis. However, the swine pathogen Chlamydia suis is commonly tetracycline resistant, both in America and in Europe. In tested U.S. strains, this resistance is mediated by a genomic island carrying a tet(C) allele. In the present study, the ability of C. suis to mobilize tet(C) into other chlamydial species was examined. Differently antibiotic resistant strains of C. suis, C. trachomatis, and Chlamydia muridarum were used in coculture experiments to select for multiply antibiotic resistant progeny. Coinfection of mammalian cells with a naturally occurring tetracycline-resistant strain of C. suis and a C. muridarum or C. trachomatis strain containing selected mutations encoding rifampin (rifampicin) or ofloxacin resistance readily produced doubly resistant recombinant clones that demonstrated the acquisition of tetracycline resistance. The resistance phenotype in the progeny from a C. trachomatis L2/ofl(R)-C. suis R19/tet(R) cross resulted from integration of a 40-kb fragment into a single ribosomal operon of a recipient, leading to a merodiploid structure containing three rRNA operons. In contrast, a cross between C. suis R19/tet(R) and C. muridarum MoPn/ofl(R) led to a classical double-crossover event transferring 99 kb of DNA from C. suis R19/tet(R) into C. muridarum MoPn/ofl(R). Tetracycline resistance was also transferred to recent clinical strains of C. trachomatis. Successful crosses were not obtained when a rifampin-resistant Chlamydophila caviae strain was used as a recipient for crosses with C. suis or C. trachomatis. These findings provide a platform for further exploration of the biology of horizontal gene transfer in Chlamydia while bringing to light potential public health concerns generated by the possibility of acquisition of tetracycline resistance by human chlamydial pathogens.
authors.affiliation: Division of Allergy and Infectious Disease, Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Suchland
authors.forename: K M
authors.initials: KM
authors.lastname: Sandoz
authors.forename: B M
authors.initials: BM
authors.lastname: Jeffrey
authors.forename: W E
authors.initials: WE
authors.lastname: Stamm
authors.forename: D D
authors.initials: DD
authors.lastname: Rockey
mesh_terms: D002689:Chlamydia / Q000187:drug effects* / Q000235:genetics; D005455:Fluorescent Antibody Technique; D022761:Gene Transfer, Horizontal; D015242:Ofloxacin / Q000494:pharmacology; D011995:Recombination, Genetic; D012293:Rifampin / Q000494:pharmacology; D013753:Tetracycline Resistance / Q000235:genetics*
chemical_list: D015242:Ofloxacin; D012293:Rifampin
references.citation: Bioinformatics. 2007 Nov 1;23(21):2942-4
references.pmid: 17893086
references.citation: Plasmid. 2002 May;47(3):172-81
references.pmid: 12151232
references.citation: J Bacteriol. 2006 Jan;188(1):275-86
references.pmid: 16352844
references.citation: Antimicrob Agents Chemother. 2004 Oct;48(10):3989-95
references.pmid: 15388463
references.citation: Antimicrob Agents Chemother. 2005 Mar;49(3):1120-6
references.pmid: 15728912
references.citation: Helicobacter. 1998 Jun;3(2):79-85
references.pmid: 9631304
references.citation: Sex Transm Dis. 2003 Apr;30(4):357-61
references.pmid: 12671559
references.citation: J Infect Dis. 1999 Mar;179 Suppl 2:S380-3
references.pmid: 10081511
references.citation: J Clin Invest. 1994 Jul;94(1):458-63
references.pmid: 8040290
references.citation: J Bacteriol. 2004 Jul;186(13):4295-306
references.pmid: 15205432
references.citation: Genome Res. 2008 Jan;18(1):161-71
references.pmid: 18032721
references.citation: Microbiology (Reading). 2007 Jan;153(Pt 1):71-9
references.pmid: 17185536
references.citation: J Bacteriol. 2008 Mar;190(5):1605-14
references.pmid: 18083799
references.citation: J Comp Pathol. 2003 May;128(4):217-44
references.pmid: 12834606
references.citation: Infect Immun. 1981 Mar;31(3):1161-76
references.pmid: 7228399
references.citation: Nucleic Acids Res. 2000 Mar 15;28(6):1397-406
references.pmid: 10684935
references.citation: Antimicrob Agents Chemother. 2003 Feb;47(2):636-42
references.pmid: 12543671
references.citation: Vet Pathol. 1999 Mar;36(2):133-7
references.pmid: 10098641
references.citation: J Infect Dis. 2000 Apr;181(4):1421-7
references.pmid: 10762573
references.citation: Pathol Biol (Paris). 1997 May;45(5):376-8
references.pmid: 9296087
references.citation: Microbes Infect. 2002 Mar;4(3):333-40
references.pmid: 11909744
references.citation: J Bacteriol. 2007 Feb;189(3):991-1003
references.pmid: 17122345
references.citation: Infect Immun. 2000 Jan;68(1):360-7
references.pmid: 10603409
references.citation: Infect Immun. 2008 Dec;76(12):5438-46
references.pmid: 18852248
references.citation: J Bacteriol. 2001 Oct;183(20):5997-6008
references.pmid: 11567000
references.citation: Vet Rec. 2008 Aug 23;163(8):251-2
references.pmid: 18723867
references.citation: Infect Immun. 1993 Jan;61(1):213-9
references.pmid: 8418043
references.citation: Adv Exp Med Biol. 2008;609:98-107
references.pmid: 18193660
references.citation: Int J Syst Evol Microbiol. 2001 Jan;51(Pt 1):203-20
references.pmid: 11211261
references.citation: J Infect Dis. 1990 Dec;162(6):1309-15
references.pmid: 2230260