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Infection and Immunity, September 2009, p. 4161-4167, Vol. 77, No. 9
0019-9567/09/$08.00+0 doi:10.1128/IAI.00189-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
,
G. S. A. Myers,3 and
P. M. Bavoil1*
Department of Microbial Pathogenesis, University of Maryland Dental School, Baltimore, Maryland,1 INRA, Infectiologie Animale et Santé Publique, Centre de Recherche de Tours, Nouzilly, France,2 Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland3
Received 18 February 2009/ Returned for modification 18 March 2009/ Accepted 30 June 2009
Comparative genomic analysis of a wild-type strain of the ovine pathogen Chlamydia abortus and its nitrosoguanidine-induced, temperature-sensitive, virulence-attenuated live vaccine derivative identified 22 single nucleotide polymorphisms unique to the mutant, including nine nonsynonymous mutations, one leading to a truncation of pmpG, which encodes a polymorphic membrane protein, and two intergenic mutations potentially affecting promoter sequences. Other nonsynonymous mutations mapped to a pmpG pseudogene and to predicted coding sequences encoding a putative lipoprotein, a sigma-54-dependent response regulator, a PhoH-like protein, a putative export protein, two tRNA synthetases, and a putative serine hydroxymethyltransferase. One of the intergenic mutations putatively affects transcription of two divergent genes encoding pyruvate kinase and a putative SOS response nuclease, respectively. These observations suggest that the temperature-sensitive phenotype and associated virulence attenuation of the vaccine strain result from disrupted metabolic activity due to altered pyruvate kinase expression and/or alteration in the function of one or more membrane proteins, most notably PmpG and a putative lipoprotein.
Published ahead of print on 13 July 2009.
Supplemental material for this article may be found at http://iai.asm.org/.
Present address: Mutabilis, Parc de Biotech, 102 Av. Gaston Roussel, F-9330 Romainville, France.
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