Journal Article

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

Purcell, Jeanette E., Martin, Dale S., Borda, Juan T., Phillippi-Falkenstein, Kathrine M., Hasenkampf, Nicole R., Philipp, Mario T., Ratterree, Marion S., Barthold, Stephen W., Bowers, Lisa, Embers, Monica E., Hodzic, Emir, Jacobs, Mary B., Narasimhan, Sukanya, Doyle, Lara

2012

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Anti-Bacterial Agents - pharmacology / Anti-Bacterial Agents - therapeutic use / Antibiotics / Antibodies / Antibody Formation - drug effects / Antibody Formation - immunology / Antigens / Bacteriology / Biology / Borrelia burgdorferi / Borrelia burgdorferi - drug effects / Care and treatment / Ceftriaxone / Deoxyribonucleic acid / Diagnosis / Diagnostic systems / Disseminated infection / DNA / DNA, Bacterial - analysis / DNA, Bacterial - genetics / Doxycycline / Experiments / Gene expression / Health aspects / Health sciences / Immunofluorescence / Immunology / Infections / Inflammation - complications / Inflammation - microbiology / Inflammation - pathology / Ixodidae / Laboratories / Lipoproteins / Lyme disease / Lyme Disease - complications / Lyme Disease - drug therapy / Lyme Disease - microbiology / Lyme Disease - pathology / Macaca mulatta / Macaca mulatta - immunology / Macaca mulatta - microbiology / Medical research / Medicine / Microbial drug resistance / Monkeys / Monkeys & apes / Parasitology / Pathogenicity / Pathogens / Penicillin / Peptides - immunology / Primates / Proteins / Ribonucleic acid / RNA / Spirochetes / Therapy / Ticks / Tissues / Treatment Outcome / Vector-borne diseases / Veterinary medicine / Xenodiagnosis