title: Persistence of Borrelia burgdorferi in rhesus macaques following antibiotic treatment of disseminated infection.
abstract: The persistence of symptoms in Lyme disease patients following antibiotic therapy, and their causes, continue to be a matter of intense controversy. The studies presented here explore antibiotic efficacy using nonhuman primates. Rhesus macaques were infected with B. burgdorferi and a portion received aggressive antibiotic therapy 4-6 months later. Multiple methods were utilized for detection of residual organisms, including the feeding of lab-reared ticks on monkeys (xenodiagnosis), culture, immunofluorescence and PCR. Antibody responses to the B. burgdorferi-specific C6 diagnostic peptide were measured longitudinally and declined in all treated animals. B. burgdorferi antigen, DNA and RNA were detected in the tissues of treated animals. Finally, small numbers of intact spirochetes were recovered by xenodiagnosis from treated monkeys. These results demonstrate that B. burgdorferi can withstand antibiotic treatment, administered post-dissemination, in a primate host. Though B. burgdorferi is not known to possess resistance mechanisms and is susceptible to the standard antibiotics (doxycycline, ceftriaxone) in vitro, it appears to become tolerant post-dissemination in the primate host. This finding raises important questions about the pathogenicity of antibiotic-tolerant persisters and whether or not they can contribute to symptoms post-treatment.
authors.affiliation: Divisions of Bacteriology & Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana, United States of America. members@tulane.edu
authors.forename: Monica E
authors.initials: ME
authors.lastname: Embers
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Barthold
authors.forename: Juan T
authors.initials: JT
authors.lastname: Borda
authors.forename: Lisa
authors.initials: L
authors.lastname: Bowers
authors.forename: Lara
authors.initials: L
authors.lastname: Doyle
authors.forename: Emir
authors.initials: E
authors.lastname: Hodzic
authors.forename: Mary B
authors.initials: MB
authors.lastname: Jacobs
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Hasenkampf
authors.forename: Dale S
authors.initials: DS
authors.lastname: Martin
authors.forename: Sukanya
authors.initials: S
authors.lastname: Narasimhan
authors.forename: Kathrine M
authors.initials: KM
authors.lastname: Phillippi-Falkenstein
authors.forename: Jeanette E
authors.initials: JE
authors.lastname: Purcell
authors.forename: Marion S
authors.initials: MS
authors.lastname: Ratterree
authors.forename: Mario T
authors.initials: MT
authors.lastname: Philipp
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D025065:Borrelia burgdorferi / Q000187:drug effects*; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D007249:Inflammation / Q000150:complications / Q000382:microbiology / Q000473:pathology; D008193:Lyme Disease / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology* / Q000473:pathology; D008253:Macaca mulatta / Q000276:immunology / Q000382:microbiology*; D010455:Peptides / Q000276:immunology; D016896:Treatment Outcome; D020525:Xenodiagnosis
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D010455:Peptides