Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection

Monica E. Embers1*, Stephen W. Barthold4, Juan T. Borda2, Lisa Bowers1, Lara Doyle3, Emir Hodzic4, Mary B. Jacobs1, Nicole R. Hasenkampf1, Dale S. Martin1, Sukanya Narasimhan5, Kathrine M. Phillippi-Falkenstein3, Jeanette E. Purcell3¤, Marion S. Ratterree3, Mario T. Philipp1*

1 Divisions of Bacteriology & Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana, United States of America, 2 Comparative Pathology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana, United States of America, 3 Veterinary Medicine, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana, United States of America, 4 Center for Comparative Medicine, Schools of Medicine and Veterinary Medicine, University of California Davis, Davis, California, United States of America, 5 Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America

Abstract Top

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. burgdorferiand 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.

Citation: Embers ME, Barthold SW, Borda JT, Bowers L, Doyle L, et al. (2012) Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection. PLoS ONE 7(1): e29914. doi:10.1371/journal.pone.0029914

Editor: Jean Louis Herrmann, Hopital Raymond Poincare - Universite Versailles St. Quentin, France

Received: July 22, 2011; Accepted: December 6, 2011; Published: January 11, 2012

Copyright: © 2012 Embers et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work was supported by NIAID grant R01-AI042352 (MTP), R01-AI26815 (SWB and EH), a TNPRC Pilot Study Grant (MEE), and NCRR grant RR00164. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

* E-mail: members@tulane.edu (MEE); Philipp@tulane.edu (MTP)

¤ Current address: Biologic Resources Laboratory, University of Illinois, Chicago, Illinois, United States of America