Genomic analysis of an attenuated Chlamydia abortus live vaccine strain reveals defects in central metabolism and surface proteins.
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.
Burall
L S
LS
Department of Microbial Pathogenesis, University of Maryland Dental School, Baltimore, Maryland 21042, USA.
Rodolakis
A
A
Rekiki
A
A
Myers
G S A
GS
Bavoil
P M
PM
D001426:Bacterial Proteins / Q000378:metabolism*; D001428:Bacterial Vaccines / Q000276:immunology*; D002511:Cephalosporins / Q000737:chemistry; D002691:Chlamydophila psittaci / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D016680:Genome, Bacterial; D012696:Glycine Hydroxymethyltransferase / Q000737:chemistry / Q000235:genetics; D008565:Membrane Proteins / Q000378:metabolism; D008718:Methionine-tRNA Ligase / Q000737:chemistry / Q000235:genetics; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D014613:Vaccines, Attenuated / Q000276:immunology; D014774:Virulence
D001426:Bacterial Proteins; D001428:Bacterial Vaccines; C489158:CB 181963; D002511:Cephalosporins; D008565:Membrane Proteins; D014613:Vaccines, Attenuated; D012696:Glycine Hydroxymethyltransferase; D008718:Methionine-tRNA Ligase