title: Borrelia burgdorferi requires glycerol for maximum fitness during the tick phase of the enzootic cycle.
abstract: Borrelia burgdorferi, the spirochetal agent of Lyme disease, is a vector-borne pathogen that cycles between a mammalian host and tick vector. This complex life cycle requires that the spirochete modulate its gene expression program to facilitate growth and maintenance in these diverse milieus. B. burgdorferi contains an operon that is predicted to encode proteins that would mediate the uptake and conversion of glycerol to dihydroxyacetone phosphate. Previous studies indicated that expression of the operon is elevated at 23°C and is repressed in the presence of the alternative sigma factor RpoS, suggesting that glycerol utilization may play an important role during the tick phase. This possibility was further explored in the current study by expression analysis and mutagenesis of glpD, a gene predicted to encode glycerol 3-phosphate dehydrogenase. Transcript levels for glpD were significantly lower in mouse joints relative to their levels in ticks. Expression of GlpD protein was repressed in an RpoS-dependent manner during growth of spirochetes within dialysis membrane chambers implanted in rat peritoneal cavities. In medium supplemented with glycerol as the principal carbohydrate, wild-type B. burgdorferi grew to a significantly higher cell density than glpD mutant spirochetes during growth in vitro at 25°C. glpD mutant spirochetes were fully infectious in mice by either needle or tick inoculation. In contrast, glpD mutants grew to significantly lower densities than wild-type B. burgdorferi in nymphal ticks and displayed a replication defect in feeding nymphs. The findings suggest that B. burgdorferi undergoes a switch in carbohydrate utilization during the mammal to tick transition. Further, the results demonstrate that the ability to utilize glycerol as a carbohydrate source for glycolysis during the tick phase of the infectious cycle is critical for maximal B. burgdorferi fitness.
authors.affiliation: Department of Microbiology and Immunology, New York Medical College, Valhalla, United States of America.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Pappas
authors.forename: Radha
authors.initials: R
authors.lastname: Iyer
authors.forename: Mary M
authors.initials: MM
authors.lastname: Petzke
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Caimano
authors.forename: Justin D
authors.initials: JD
authors.lastname: Radolf
authors.forename: Ira
authors.initials: I
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D025065:Borrelia burgdorferi / Q000254:growth & development* / Q000472:pathogenicity; D004195:Disease Models, Animal; D015964:Gene Expression Regulation, Bacterial; D005990:Glycerol / Q000378:metabolism*; D050536:Glycerol-3-Phosphate Dehydrogenase (NAD+) / Q000235:genetics / Q000378:metabolism; D006614:Hindlimb; D054884:Host-Pathogen Interactions; D018884:Ixodes / Q000382:microbiology*; D007596:Joints / Q000201:enzymology / Q000382:microbiology; D008193:Lyme Disease; D051379:Mice; D008809:Mice, Inbred C3H; D051381:Rats; D017207:Rats, Sprague-Dawley; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D012808:Sigma Factor; C069567:sigma factor KatF protein, Bacteria; D050536:Glycerol-3-Phosphate Dehydrogenase (NAD+); D005990:Glycerol