Constitutive SOS expression and damage-inducible AddAB-mediated recombinational repair systems for Coxiella burnetii as potential adaptations for survival within macrophages.
Coxiella burnetii, a Gram-negative obligate intracellular pathogen, replicates within an parasitophorous vacuole with lysosomal characteristics. To understand how C. burnetii maintains genomic integrity in this environment, a database search for genes involved in DNA repair was performed. Major components of repair, SOS response and recombination were identified, including recA and ruvABC, but lexA and recBCD were absent. Instead, C. burnetii possesses addAB orthologous genes, functional equivalents to recBCD. Survival after treatment with UV, mitomycin C (MC) or methyl methanesulfonate (MMS), as well as homologous recombination in Hfr mating was restored in Escherichia coli deletion strains by C. burnetii recA or addAB. Despite the absence of LexA, co-protease activity for C. burnetii RecA was demonstrated. Dominant-negative inhibition of C. burnetii RecA by recA mutant alleles, modelled after E. coli recA1 and recA56, was observed and more apparent with expression of C. burnetii RecAG159D mutant protein. Expression of a subset of repair genes in C. burnetii was monitored and, in contrast to the non-inducible E. coli recBCD, addAB expression was strongly upregulated under oxidative stress. Constitutive SOS gene expression due to the lack of LexA and induction of AddAB likely reflect a unique repair adaptation of C. burnetii to its hostile niche.
Mertens
Katja
K
Department of Microbial and Molecular Pathogenesis, Texas A&M Health Science Center, College of Medicine, College Station, TX, USA.
Lantsheer
Letty
L
Ennis
Don G
DG
Samuel
James E
JE
D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D002460:Cell Line; D016997:Coxiella burnetii / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D004249:DNA Damage; D004926:Escherichia coli / Q000235:genetics; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D008264:Macrophages / Q000382:microbiology*; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D051379:Mice; D050296:Microbial Viability; D016685:Mitomycin / Q000494:pharmacology; D008969:Molecular Sequence Data; D009153:Mutagens / Q000494:pharmacology; D011938:Rec A Recombinases / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D013014:SOS Response, Genetics; D016415:Sequence Alignment; D014466:Ultraviolet Rays
D001426:Bacterial Proteins; D009153:Mutagens; D016685:Mitomycin; D008741:Methyl Methanesulfonate; D011938:Rec A Recombinases; D005090:Exodeoxyribonucleases; C407424:AddAB enzyme