Lyme Borreliosis: Is there a preexisting (natural) variation in antimicrobial susceptibility among Borrelia burgdorferi strains?

  • Emir Hodzic Real-Time PCR Research & Diagnostics Core Facility, School of Veterinary Medicine, University of California, Davis
Keywords: Borrelia burgdorferi, antibiotics, persistence, antimicrobial resistance, antimicrobial tolerance, ticks, small mammals

Abstract

The development of antibiotics changed the world of medicine and has saved countless human and animal lives. Bacterial resistance/tolerance to antibiotics have spread silently across the world and has emerged as a major public health concern. The recent emergence of pan-resistant bacteria can overcome virtually any antibiotic and poses a major problem for their successful control. Selection for antibiotic resistance may take place where an antibiotic is present: in the skin, gut, and other tissues of humans and animals and in the environment. Borrelia burgdorferi, the etiological agents of Lyme borreliosis, evades host immunity and establishes persistent infections in its mammalian hosts. The persistent infection poses a challenge to the effective antibiotic treatment, as demonstrated in various animal models. An increasingly heterogeneous subpopulation of replicatively attenuated spirochetes arises following treatment, and these persistent antimicrobial tolerant/resistant spirochetes are non-cultivable. The non-cultivable spirochetes resurge in multiple tissues at 12 months after treatment, with B. burgdorferi-specific DNA copy levels nearly equivalent to those found in shame-treated experimental animals. These attenuated spirochetes remain viable, but divide slowly, thereby being tolerant to antibiotics. Despite the continued non-cultivable state, RNA transcription of multiple B. burgdorferi genes was detected in host tissues, spirochetes were acquired by xenodiagnostic ticks, and spirochetal forms could be visualized within ticks and mouse tissues. A number of host cytokines were up- or down-regulated in tissues of both shame- and antibiotic-treated mice in the absence of histopathology, indicating a lack of host response to the presence of antimicrobial tolerant/resistant spirochetes.

 

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Author Biography

Emir Hodzic, Real-Time PCR Research & Diagnostics Core Facility, School of Veterinary Medicine, University of California, Davis
Director, Real-Time PCR Research & Diagnostics Core Facility
School of Veterinary Medicine
University of California, Davis

References

Steere AC, Malawista SE, Snydman DR, Shope RE, Andiman WA, Ross MR, et al. Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three connecticut communities. Arthritis Rheum. 1977 Jan-Feb;20(1):7-17.

http://dx.doi.org/10.1002/art.1780200102

Burgdorfer W, Barbour AG, Hayes SF, Benach JL, Grunwaldt E, Davis JP. Lyme disease-a tick-borne spirochetosis? Science. 1982 Jun 18;216(4552):1317-9.

http://dx.doi.org/10.1126/science.7043737

Johnson RC, Hyde FW, Rumpel CM. Taxonomy of the Lyme disease spirochetes. Yale J Biol Med. 1984 Jul-Aug;57(4):529-37.

Johnson RC, Schmid GP, Hyde FW, Steigerwalt AG, Brenner DJ. Borrelia burgdorferi sp. nov.: etiological agent of Lyme disease. Int J System Bacteriol. 1984;34(4):496-7.

http://dx.doi.org/10.1099/00207713-34-4-496

Benach J, Garcia Monco J. The Woldwide Saga of Lyme Borreliosis. In: Samuels SD, Radolf J, editors. Borrelia, Molecular Biology, Host Interaction and Pathogenesis. Norfolk, UK: Caister Academic Press; 2010. p. 21-40.

Humair P, Gern L. The wild hidden face of Lyme borreliosis in Europe. Microbes Infect. 2000 Jul;2(8):915-22.

http://dx.doi.org/10.1016/S1286-4579(00)00393-2

Roberts DM, Carlyon JA, Theisen M, Marconi RT. The bdr gene families of the Lyme disease and relapsing fever spirochetes: potential influence on biology, pathogenesis, and evolution. Emerg Infect Dis. 2000 Mar-Apr;6(2):110-22.

http://dx.doi.org/10.3201/eid0602.000203

Sigal LH. Summary of the Fifth International Congress on Lyme Borreliosis. Arthritis Rheum. 1994 Jan;37(1):10-4.

http://dx.doi.org/10.1002/art.1780370103

Smith R, O'Connell S, Palmer S. Lyme disease surveillance in England and Wales, 1986 1998. Emerg Infect Dis. 2000 Jul-Aug;6(4):404-7.

http://dx.doi.org/10.3201/eid0604.000416

Rizzoli A, Hauffe H, Carpi G, Vourc HG, Neteler M, Rosa R. Lyme borreliosis in Europe. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin. 2011;16(27).

Lischer CJ, Leutenegger CM, Braun U, Lutz H. Diagnosis of Lyme disease in two cows by the detection of Borrelia burgdorferi DNA. Vet Rec. 2000 Apr 22;146(17):497-9.

http://dx.doi.org/10.1136/vr.146.17.497

Magnarelli LA, Ijdo JW, Van Andel AE, Wu C, Padula SJ, Fikrig E. Serologic confirmation of Ehrlichia equi and Borrelia burgdorferi infections in horses from the northeastern United States. J Am Vet Med Assoc. 2000;217(7):1045-50.

http://dx.doi.org/10.2460/javma.2000.217.1045

Tuomi J, Rantamaki LK, Tanskanen R. Experimental infection of laboratory mice and rabbits with several isolates of Borrelia burgdorferi sensu lato; comparison of antigens from different genospecies in serological measurement of immune responses. Comp Immunol Microbiol Infect Dis. 2002;25(2):109-25.

http://dx.doi.org/10.1016/S0147-9571(01)00027-3

Telford SR, 3rd, Armstrong PM, Katavolos P, Foppa I, Garcia AS, Wilson ML, et al. A new tick-borne encephalitis-like virus infecting New England deer ticks, Ixodes dammini. Emerg Infect Dis. 1997 Apr-Jun;3(2):165-70.

http://dx.doi.org/10.3201/eid0302.970209

Barbour AG, Hayes SF. Biology of Borrelia species. Microbiol Rev. 1986 Dec;50(4):381-400.

Barbour AG. Isolation and cultivation of Lyme disease spirochetes. Yale J Biol Med. 1984 Jul-Aug;57(4):521-5.

Hayes SF, Burgdorfer W. II Characteristics of Borrelia burgdorferi. 3 Ultrastructure of Borrelia burgdorferi. In: Weber K, Burgdorfer W, Schierz G, editors. Aspects of Lyme Borreliosis. Berlin, Heidelberg, New York, London, Paris, Tokyo, Hong Kong, Barcelona, Budapest Springer-Verlag 1993. p. 29-43.

http://dx.doi.org/10.1007/978-3-642-77614-4_3

Casjens SR, Eggers CH, Schwartz I. Borrelia Genomics: Chromosome, Plasmids, Bacteriphages and Genetic Variation. In: Samuels SD, Radolf J, editors. Borrelia; Molecular Biology, Host Interaction and Pathogenesis. Norfolk, UK: Caister Academic Press; 2010. p. 21-47.

Dykhuizen D, Brisson D. Evolutionary Genetics of Borrelia burgdorferi sensu lato. In: Samuels SD, Radolf J, editors. Borrelia; Molecular Biology, Host Interaction and Pathogenesis. Norfolk, UK: Caister Academic Press; 2010. p. 215-43.

Norris DE, Coburn J, Leong JM, Hu LT, Hook M. Pathobiology of Lyme Disease Borrelia. In: Samuels DS, Radolf J, editors. Borrelia: Molecular Biology, Host Interaction and Pathogenesis. Norfolk, UK: Caister Academic Press; 2010. p. 295-325.

Daix V, Schroeder H, Praet N, Georgin JP, Chiappino I, Gillet L, et al. Ixodes ticks belonging to the Ixodes ricinus complex encode a family of anticomplement proteins. Insect Mol Biol. 2007 Apr;16(2):155-66.

http://dx.doi.org/10.1111/j.1365-2583.2006.00710.x

Radolf JD, Caimano MJ, Stevenson B, Hu LT. Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes. Nat Rev Microbiol. 2012 Feb;10(2):87-99.

http://dx.doi.org/10.1038/nrmicro2714

Piesman J, Schwan T. Ecology of Borreliae and their Arthropod Vectors. In: Samuels SD, Radolf J, editors. Borrelia; Molecular Biology, Host Interaction and Pathogenesis. Norfolk, UK: Caister Academic Press; 2010. p. 245-72.

Madigan JE. Lyme disease (Lyme borreliosis) in horses. Vet Clin North Am Equine Pract. 1993 Aug;9(2):429-34.

Parker JL, White KK. Lyme borreliosis in cattle and horses: a review of the literature. Cornell Vet. 1992 Jul;82(3):253-74.

Schmidtmann ET, Schlater JL, Maupin GO, Mertins JW. Vegetational association of host-seeking adult blacklegged ticks, Ixodes scapularis Say (Acari: Ixodidae), on dairy farms in northwestern Wisconsin. J Dairy Sci. 1998 Mar;81(3):718-21.

http://dx.doi.org/10.3168/jds.S0022-0302(98)75627-9

Anderson JF, Magnarelli LA. Epizootiology of Lyme disease-causing borreliae. Clin Dermatol. 1993 Jul-Sep;11(3):339-51.

http://dx.doi.org/10.1016/0738-081X(93)90088-T

Spielman A, Levine JF, Wilson ML. Vectorial capacity of North American Ixodes ticks. Yale J Biol Med. 1984 Jul-Aug;57(4):507-13.

Peavey CA, Lane RS. Transmission of Borrelia burgdorferi by Ixodes pacificus nymphs and reservoir competence of deer mice (Peromyscus maniculatus) infected by tick-bite. J Parasitol. 1995;81(2):175-8.

http://dx.doi.org/10.2307/3283916

Olsen B, Duffy DC, Jaenson TG, Gylfe A, Bonnedahl J, Bergstrom S. Transhemispheric exchange of Lyme disease spirochetes by seabirds. J Clin Microbiol. 1995 Dec;33(12):3270-4.

Bacon RM, Kugeler KJ, Mead PS. Surveillance for Lyme disease--United States, 1992-2006. MMWR Surveill Summ. 2008 Oct 3;57(10):1-9.

Nuttall PA. Displaced tick-parasite interactions at the host interface. Parasitology. 1998;116(Suppl):S65-72.

http://dx.doi.org/10.1017/S003118200008495X

De Silva AM, Fikrig E. Growth and migration of Borrelia burgdorferi in Ixodes ticks during blood feeding. Am J Trop Med Hyg. 1995;53(4):397-404.

Schwan TG, Piesman J, Golde WT, Dolan MC, Rosa PA. Induction of an outer surface protein on Borrelia burgdorferi during tick feeding. Proc Natl Acad Sci U S A. 1995;92(7):2909-13.

http://dx.doi.org/10.1073/pnas.92.7.2909

Hodzic E, Feng S, Freet KJ, Barthold SW. Borrelia burgdorferi population dynamics and prototype gene expression during infection of immunocompetent and immunodeficient mice. Infect Immun. 2003 Sep;71(9):5042-55.

http://dx.doi.org/10.1128/IAI.71.9.5042-5055.2003

Hodzic E, Borjesson DL, Feng S, Barthold SW. Acquisition dynamics of Borrelia burgdorferi and the agent of human granulocytic ehrlichiosis at the host-vector interface. Vector Borne Zoonotic Dis. 2001 Summer;1(2):149-58.

http://dx.doi.org/10.1089/153036601316977750

Hodzic E, Feng S, Fish D, Leutenegger CM, Freet KJ, Barthold SW. Infection of mice with the agent of human granulocytic ehrlichiosis after different routes of inoculation. J Infect Dis. 2001 Jun 15;183(12):1781-6.

http://dx.doi.org/10.1086/320735

Shih CM, Pollack RJ, Telford SR, 3rd, Spielman A. Delayed dissemination of Lyme disease spirochetes from the site of deposition in the skin of mice. J Infect Dis. 1992;166(4):827-31.

http://dx.doi.org/10.1093/infdis/166.4.827

Marques A. Chronic Lyme disease: a review. Infect Dis Clin North Am. 2008 Jun;22(2):341-60, vii-viii.

http://dx.doi.org/10.1016/j.idc.2007.12.011

Steere AC, Sikand VK. The presenting manifestations of Lyme disease and the outcomes of treatment. N Engl J Med. 2003 Jun 12;348(24):2472-4.

http://dx.doi.org/10.1056/NEJM200306123482423

Steere AC, Coburn J, Glickstein L. The emergence of Lyme disease. J Clin Invest. 2004 Apr;113(8):1093-101.

http://dx.doi.org/10.1172/JCI21681

Nadelman RB. Erythema Migrans. Infect Dis Clin North Am. 2015 Jun;29(2):211-39.

http://dx.doi.org/10.1016/j.idc.2015.02.001

Barthold SW. Lyme borreliosis. In: Nataro JP, Blaser MJ, Cunningham-Rundles S, editors. Persistent bacterial infection. Washington, DC: ASM Press; 2000. p. 281-304.

http://dx.doi.org/10.1128/9781555818104.ch14

Barthold SW, Fikrig E, Bockenstedt LK, Persing DH. Circumvention of outer surface protein A immunity by host-adapted Borrelia burgdorferi. Infect Immun. 1995;63(6):2255-61.

Montgomery RR, Malawista SE, Feen KJ, Bockenstedt LK. Direct demonstration of antigenic substitution of Borrelia burgdorferi ex vivo: exploration of the paradox of the early immune response to outer surface proteins A and C in Lyme disease. J Exp Med. 1996;183(1):261-9.

http://dx.doi.org/10.1084/jem.183.1.261

Srivastava SY, de Silva AM. Reciprocal expression of ospA and ospC in single cells of Borrelia burgdorferi. J Bacteriol. 2008 May;190(10):3429-33.

http://dx.doi.org/10.1128/JB.00085-08

Pulzova L, Bhide M. Outer surface proteins of Borrelia: peerless immune evasion tools. Curr Protein Pept Sci. 2014 Feb;15(1):75-88.

http://dx.doi.org/10.2174/1389203715666140221124213

Montgomery RR, Nathanson MH, Malawista SE. The fate of Borrelia burgdorferi, the agent for Lyme disease, in mouse macrophages. Destruction, survival, recovery. J Immunol. 1993;150(3):909-15.

Pachner AR, Basta J, Delaney E, Hulinska D. Localization of Borrelia burgdorferi in murine Lyme borreliosis by electron microscopy. Am J Trop Med Hyg. 1995;52(2):128-33.

Hulinska D, Bartak P, Hercogova J, Hancil J, Basta J, Schramlova J. Electron microscopy of Langerhans cells and Borrelia burgdorferi in Lyme disease patients. Zentralbl Bakteriol. 1994 Jan;280(3):348-59.

http://dx.doi.org/10.1016/S0934-8840(11)80597-9

Brorson O, Brorson SH. In vitro conversion of Borrelia burgdorferi to cystic forms in spinal fluid, and transformation to mobile spirochetes by incubation in BSK-H medium. Infection. 1998;26(3):144-50.

http://dx.doi.org/10.1007/BF02771839

Alban PS, Johnson PW, Nelson DR. Serum-starvation-induced changes in protein synthesis and morphology of Borrelia burgdorferi. Microbiology. 2000 Jan;146 (Pt 1):119-27.

Kraiczy P, Hanssen-Hubner C, Kitiratschky V, Brenner C, Besier S, Brade V, et al. Mutational analyses of the BbCRASP-1 protein of Borrelia burgdorferi identify residues relevant for the architecture and binding of host complement regulators FHL-1 and factor H. Int J Med Microbiol. 2009 Apr;299(4):255-68.

http://dx.doi.org/10.1016/j.ijmm.2008.09.002

Sapi E, Bastian SL, Mpoy CM, Scott S, Rattelle A, Pabbati N, et al. Characterization of biofilm formation by Borrelia burgdorferi in vitro. PLoS One. 2012;7(10):e48277.

http://dx.doi.org/10.1371/journal.pone.0048277

Arvikar SL, Steere AC. Diagnosis and Treatment of Lyme Arthritis. Infect Dis Clin North Am. 2015 Jun;29(2):269-80.

http://dx.doi.org/10.1016/j.idc.2015.02.004

Robinson ML, Kobayashi T, Higgins Y, Calkins H, Melia MT. Lyme Carditis. Infect Dis Clin North Am. 2015 Jun;29(2):255-68.

http://dx.doi.org/10.1016/j.idc.2015.02.003

Porcella SF, Schwan TG. Borrelia burgdorferi and Treponema pallidum: a comparison of functional genomics, environmental adaptations, and pathogenic mechanisms. J Clin Invest. 2001;107(6):651-6.

http://dx.doi.org/10.1172/JCI12484

Liang FT, Nelson FK, Fikrig E. DNA Microarray Assessment of Putative Borrelia burgdorferi Lipoprotein Genes. Infect Immun. 2002;70(6):3300-3.

http://dx.doi.org/10.1128/IAI.70.6.3300-3303.2002

Labandeira-Rey M, Seshu J, Skare JT. The absence of linear plasmid 25 or 28-1 of Borrelia burgdorferi dramatically alters the kinetics of experimental infection via distinct mechanisms. Infect Immun. 2003 Aug;71(8):4608-13.

http://dx.doi.org/10.1128/IAI.71.8.4608-4613.2003

Labandeira-Rey M, Skare JT. Decreased infectivity in Borrelia burgdorferi strain B31 is associated with loss of linear plasmid 25 or 28-1. Infect Immun. 2001;69(1):446-55.

http://dx.doi.org/10.1128/IAI.69.1.446-455.2001

Purser JE, Norris SJ. Correlation between plasmid content and infectivity in Borrelia burgdorferi. Proc Natl Acad Sci U S A. 2000;97(25):13865-70.

http://dx.doi.org/10.1073/pnas.97.25.13865

Thomas V, Anguita J, Samanta S, Rosa PA, Stewart P, Barthold SW, et al. Dissociation of infectivity and pathogenicity in Borrelia burgdorferi. Infect Immun. 2001;69(5):3507-9.

http://dx.doi.org/10.1128/IAI.69.5.3507-3509.2001

Bockenstedt LK, Mao J, Hodzic E, Barthold SW, Fish D. Detection of attenuated, noninfectious spirochetes in Borrelia burgdorferi-infected mice after antibiotic treatment. J Infect Dis. 2002 Nov 15;186(10):1430-7.

http://dx.doi.org/10.1086/345284

Fraser CM, Casjens S, Huang WM, Sutton GG, Clayton R, Lathigra R, et al. Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature. 1997;390(6660):580-6.

http://dx.doi.org/10.1038/37551

Dulebohn DP, Bestor A, Rego RO, Stewart PE, Rosa PA. Borrelia burgdorferi linear plasmid 38 is dispensable for completion of the mouse-tick infectious cycle. Infect Immun. 2011 Sep;79(9):3510-7.

http://dx.doi.org/10.1128/IAI.05014-11

Schwan TG, Burgdorfer W, Schrumpf ME, Karstens RH. The urinary bladder, a consistent source of Borrelia burgdorferi in experimentally infected white-footed mice (Peromyscus leucopus). J Clin Microbiol. 1988;26(5):893-5.

Barthold SW, de Souza MS, Janotka JL, Smith AL, Persing DH. Chronic Lyme borreliosis in the laboratory mouse. Am J Pathol. 1993;143(3):959-71.

Moody KD, Barthold SW, Terwilliger GA, Beck DS, Hansen GM, Jacoby RO. Experimental chronic Lyme borreliosis in Lewis rats. Am J Trop Med Hyg. 1990;42(2):165-74.

Goodman JL, Jurkovich P, Kodner C, Johnson RC. Persistent cardiac and urinary tract infections with Borrelia burgdorferi in experimentally infected Syrian hamsters. J Clin Microbiol. 1991 May;29(5):894-6.

Preac Mursic V, Patsouris E, Wilske B, Reinhardt S, Gross B, Mehraein P. Persistence of Borrelia burgdorferi and histopathological alterations in experimentally infected animals. A comparison with histopathological findings in human Lyme disease. Infection. 1990 Nov-Dec;18(6):332-41.

http://dx.doi.org/10.1007/BF01646399

Sonnesyn SW, Manivel JC, Johnson RC, Goodman JL. A guinea pig model for Lyme disease. Infect Immun. 1993 Nov;61(11):4777-84.

Straubinger RK, Summers BA, Chang YF, Appel MJ. Persistence of Borrelia burgdorferi in experimentally infected dogs after antibiotic treatment. J Clin Microbiol. 1997 Jan;35(1):111-6.

Roberts ED, Bohm RP, Jr., Cogswell FB, Lanners HN, Lowrie RC, Jr., Povinelli L, et al. Chronic lyme disease in the rhesus monkey. Lab Invest. 1995 Feb;72(2):146-60.

Asbrink E, Hovmark A. Successful cultivation of spirochetes from skin lesions of patients with erythema chronicum migrans Afzelius and acrodermatitis chronica atrophicans. Acta Pathol Microbiol Immunol Scand B. 1985 Apr;93(2):161-3.

http://dx.doi.org/10.1111/j.1699-0463.1985.tb02870.x

Kuiper H, van Dam AP, Spanjaard L, de Jongh BM, Widjojokusumo A, Ramselaar TC, et al. Isolation of Borrelia burgdorferi from biopsy specimens taken from healthy-looking skin of patients with Lyme borreliosis. J Clin Microbiol. 1994 Mar;32(3):715-20.

Maraspin V, Ogrinc K, Ruzic-Sabljic E, Lotric-Furlan S, Strle F. Isolation of Borrelia burgdorferi sensu lato from blood of adult patients with borrelial lymphocytoma, Lyme neuroborreliosis, Lyme arthritis and acrodermatitis chronica atrophicans. Infection. 2011 Feb;39(1):35-40.

http://dx.doi.org/10.1007/s15010-010-0062-8

Miklossy J, Khalili K, Gern L, Ericson RL, Darekar P, Bolle L, et al. Borrelia burgdorferi persists in the brain in chronic lyme neuroborreliosis and may be associated with Alzheimer disease. J Alzheimers Dis. 2004 Dec;6(6):639-49; discussion 73-81.

Snydman DR, Schenkein DP, Berardi VP, Lastavica CC, Pariser KM. Borrelia burgdorferi in joint fluid in chronic Lyme arthritis. Ann Intern Med. 1986 Jun;104(6):798-800.

http://dx.doi.org/10.7326/0003-4819-104-6-798

Stanek G, Klein J, Bittner R, Glogar D. Isolation of Borrelia burgdorferi from the myocardium of a patient with longstanding cardiomyopathy. N Engl J Med. 1990 Jan 25;322(4):249-52.

http://dx.doi.org/10.1056/NEJM199001253220407

Strle F, Cheng Y, Cimperman J, Maraspin V, Lotric-Furlan S, Nelson JA, et al. Persistence of Borrelia burgdorferi sensu lato in resolved erythema migrans lesions. Clin Infect Dis. 1995 Aug;21(2):380-9.

http://dx.doi.org/10.1093/clinids/21.2.380

Bradley JF, Johnson RC, Goodman JL. The persistence of spirochetal nucleic acids in active Lyme arthritis. Ann Intern Med. 1994 Mar 15;120(6):487-9.

http://dx.doi.org/10.7326/0003-4819-120-6-199403150-00007

Fraser DD, Kong LI, Miller FW. Molecular detection of persistent Borrelia burgdorferi in a man with dermatomyositis. Clin Exp Rheumatol. 1992 Jul-Aug;10(4):387-90.

Moter SE, Hofmann H, Wallich R, Simon MM, Kramer MD. Detection of Borrelia burgdorferi sensu lato in lesional skin of patients with erythema migrans and acrodermatitis chronica atrophicans by ospA-specific PCR. J Clin Microbiol. 1994 Dec;32(12):2980-8.

Nocton JJ, Dressler F, Rutledge BJ, Rys PN, Persing DH, Steere AC. Detection of Borrelia burgdorferi DNA by polymerase chain reaction in synovial fluid from patients with Lyme arthritis. N Engl J Med. 1994 Jan 27;330(4):229-34.

http://dx.doi.org/10.1056/NEJM199401273300401

von Stedingk LV, Olsson I, Hanson HS, Asbrink E, Hovmark A. Polymerase chain reaction for detection of Borrelia burgdorferi DNA in skin lesions of early and late Lyme borreliosis. Eur J Clin Microbiol Infect Dis. 1995 Jan;14(1):1-5.

http://dx.doi.org/10.1007/BF02112610

Cabello FC, Godfrey HP, Newman SA. Hidden in plain sight: Borrelia burgdorferi and the extracellular matrix. Trends Microbiol. 2007 Aug;15(8):350-4.

http://dx.doi.org/10.1016/j.tim.2007.06.003

Hodzic E, Feng S, Holden K, Freet KJ, Barthold SW. Persistence of Borrelia burgdorferi following antibiotic treatment in mice. Antimicrob Agents Chemother. 2008 May;52(5):1728-36.

http://dx.doi.org/10.1128/AAC.01050-07

Barthold SW, Hodzic E, Tunev S, Feng S. Antibody-mediated disease remission in the mouse model of lyme borreliosis. Infect Immun. 2006 Aug;74(8):4817-25.

http://dx.doi.org/10.1128/IAI.00469-06

Liang FT, Brown EL, Wang T, Iozzo RV, Fikrig E. Protective niche for Borrelia burgdorferi to evade humoral immunity. Am J Pathol. 2004 Sep;165(3):977-85.

http://dx.doi.org/10.1016/S0002-9440(10)63359-7

Steere AC. Lyme disease. N Engl J Med. 2001 Jul 12;345(2):115-25.

http://dx.doi.org/10.1056/NEJM200107123450207

Steere AC, Schoen RT, Taylor E. The clinical evolution of Lyme arthritis. Ann Intern Med. 1987 Nov;107(5):725-31.

http://dx.doi.org/10.7326/0003-4819-107-5-725

Barthold SW, deSouza M, Feng S. Serum-mediated resolution of Lyme arthritis in mice. Lab Invest. 1996;74(1):57-67.

Barthold SW, Feng S, Bockenstedt LK, Fikrig E, Feen K. Protective and arthritis-resolving activity in sera of mice infected with Borrelia burgdorferi. Clin Infect Dis. 1997;25(Suppl 1):S9-17.

http://dx.doi.org/10.1086/516166

Wormser GP, Nadelman RB, Dattwyler RJ, Dennis DT, Shapiro ED, Steere AC, et al. Practice guidelines for the treatment of Lyme disease. The Infectious Diseases Society of America. Clin Infect Dis. 2000 Jul;31 Suppl 1:1-14.

http://dx.doi.org/10.1086/314053

Wormser GP, Ramanathan R, Nowakowski J, McKenna D, Holmgren D, Visintainer P, et al. Duration of antibiotic therapy for early Lyme disease. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2003 May 6;138(9):697-704.

http://dx.doi.org/10.7326/0003-4819-138-9-200305060-00005

Bockenstedt LK, Radolf JD. Xenodiagnosis for posttreatment Lyme disease syndrome: resolving the conundrum or adding to it? Clin Infect Dis. 2014 Apr;58(7):946-8.

http://dx.doi.org/10.1093/cid/cit942

Feder HM, Jr., Johnson BJ, O'Connell S, Shapiro ED, Steere AC, Wormser GP, et al. A critical appraisal of "chronic Lyme disease". N Engl J Med. 2007 Oct 4;357(14):1422-30.

http://dx.doi.org/10.1056/NEJMra072023

Gaubitz M, Dressler F, Huppertz HI, Krause A, Kommission Pharmakotherapie der D. [Diagnosis and treatment of Lyme arthritis. Recommendations of the Pharmacotherapy Commission of the Deutsche Gesellschaft fur Rheumatologie (German Society for Rheumatology)]. Z Rheumatol. 2014 Jun;73(5):469-74.

http://dx.doi.org/10.1007/s00393-014-1370-7

Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006 Nov 1;43(9):1089-134.

http://dx.doi.org/10.1086/508667

Lantos PM, Charini WA, Medoff G, Moro MH, Mushatt DM, Parsonnet J, et al. Final report of the Lyme disease review panel of the Infectious Diseases Society of America. Clin Infect Dis. 2010 Jul 1;51(1):1-5.

http://dx.doi.org/10.1086/654809

Baker PJ. Chronic Lyme disease: in defense of the scientific enterprise. FASEB J. 2010 Nov;24(11):4175-7.

http://dx.doi.org/10.1096/fj.10-167247

Nadelman RB, Nowakowski J, Forseter G, Goldberg NS, Bittker S, Cooper D, et al. The clinical spectrum of early Lyme borreliosis in patients with culture-confirmed erythema migrans. Am J Med. 1996 May;100(5):502-8.

http://dx.doi.org/10.1016/S0002-9343(95)99915-9

Stanek G, Strle F. Lyme borreliosis. Lancet. 2003 Nov 15;362(9396):1639-47.

http://dx.doi.org/10.1016/S0140-6736(03)14798-8

Tonks A. Lyme wars. BMJ. 2007 Nov 3;335(7626):910-2.

http://dx.doi.org/10.1136/bmj.39363.530961.AD

Adams KN, Takaki K, Connolly LE, Wiedenhoft H, Winglee K, Humbert O, et al. Drug tolerance in replicating mycobacteria mediated by a macrophage-induced efflux mechanism. Cell. 2011 Apr 1;145(1):39-53.

http://dx.doi.org/10.1016/j.cell.2011.02.022

Allison KR, Brynildsen MP, Collins JJ. Metabolite-enabled eradication of bacterial persisters by aminoglycosides. Nature. 2011 May 12;473(7346):216-20.

http://dx.doi.org/10.1038/nature10069

Aminov RI, Mackie RI. Evolution and ecology of antibiotic resistance genes. FEMS Microbiol Lett. 2007 Jun;271(2):147-61.

http://dx.doi.org/10.1111/j.1574-6968.2007.00757.x

Boumart Z, Roche SM, Lalande F, Virlogeux-Payant I, Hennequet-Antier C, Menanteau P, et al. Heterogeneity of persistence of Salmonella enterica serotype Senftenberg strains could explain the emergence of this serotype in poultry flocks. PLoS One. 2012;7(4):e35782.

http://dx.doi.org/10.1371/journal.pone.0035782

Gullberg E, Cao S, Berg OG, Ilback C, Sandegren L, Hughes D, et al. Selection of resistant bacteria at very low antibiotic concentrations. PLoS Pathog. 2011 Jul;7(7):e1002158.

http://dx.doi.org/10.1371/journal.ppat.1002158

Hamad MA, Austin CR, Stewart AL, Higgins M, Vazquez-Torres A, Voskuil MI. Adaptation and antibiotic tolerance of anaerobic Burkholderia pseudomallei. Antimicrob Agents Chemother. 2011 Jul;55(7):3313-23.

http://dx.doi.org/10.1128/AAC.00953-10

Kozak GK, Boerlin P, Janecko N, Reid-Smith RJ, Jardine C. Antimicrobial resistance in Escherichia coli isolates from swine and wild small mammals in the proximity of swine farms and in natural environments in Ontario, Canada. Appl Environ Microbiol. 2009 Feb;75(3):559-66.

http://dx.doi.org/10.1128/AEM.01821-08

Nessar R, Cambau E, Reyrat JM, Murray A, Gicquel B. Mycobacterium abscessus: a new antibiotic nightmare. J Antimicrob Chemother. 2012 Apr;67(4):810-8.

http://dx.doi.org/10.1093/jac/dkr578

Roberts RR, Hota B, Ahmad I, Scott RD, 2nd, Foster SD, Abbasi F, et al. Hospital and societal costs of antimicrobial-resistant infections in a Chicago teaching hospital: implications for antibiotic stewardship. Clin Infect Dis. 2009 Oct 15;49(8):1175-84.

http://dx.doi.org/10.1086/605630

Boxall AB. The environmental side effects of medication. EMBO Rep. 2004 Dec;5(12):1110-6.

http://dx.doi.org/10.1038/sj.embor.7400307

Sandegren L. Selection of antibiotic resistance at very low antibiotic concentrations. Upsala journal of medical sciences. 2014 May;119(2):103-7.

http://dx.doi.org/10.3109/03009734.2014.904457

Thiele-Bruhn S. Pharmaceutical antibiotic compounds in soils - a review. j Plant Nutr Soil Sci. 2003 February 11, 2003(155):145-67.

Bonnedahl J, Jarhult JD. Antibiotic resistance in wild birds. Upsala journal of medical sciences. 2014 May;119(2):113-6.

http://dx.doi.org/10.3109/03009734.2014.905663

Levy SB, Marshall B. Antibacterial resistance worldwide: causes, challenges and responses. Nat Med. 2004 Dec;10(12 Suppl):S122-9.

http://dx.doi.org/10.1038/nm1145

Lloyd DH. Reservoirs of antimicrobial resistance in pet animals. Clin Infect Dis. 2007 Sep 1;45 Suppl 2:S148-52.

http://dx.doi.org/10.1086/519254

Nkogwe C, Raletobana J, Stewart-Johnson A, Suepaul S, Adesiyun A. Frequency of Detection of Escherichia coli, Salmonella spp., and Campylobacter spp. in the Faeces of Wild Rats (Rattus spp.) in Trinidad and Tobago. Veterinary medicine international. 2011;2011:686923.

Pichon B, Egan D, Rogers M, Gray J. Detection and identification of pathogens and host DNA in unfed host-seeking Ixodes ricinus L. (Acari: Ixodidae). J Med Entomol. 2003 Sep;40(5):723-31.

http://dx.doi.org/10.1603/0022-2585-40.5.723

Zurek L, Ghosh A. Insects represent a link between food animal farms and the urban environment for antibiotic resistance traits. Appl Environ Microbiol. 2014 Jun;80(12):3562-7.

http://dx.doi.org/10.1128/AEM.00600-14

Wardyn SE, Kauffman LK, Smith TC. Methicillin-resistant Staphylococcus aureus in central Iowa wildlife. J Wildl Dis. 2012 Oct;48(4):1069-73.

http://dx.doi.org/10.7589/2011-10-295

Moodley A, Guardabassi L. Transmission of IncN plasmids carrying blaCTX-M-1 between commensal Escherichia coli in pigs and farm workers. Antimicrob Agents Chemother. 2009 Apr;53(4):1709-11.

http://dx.doi.org/10.1128/AAC.01014-08

van Loo I, Huijsdens X, Tiemersma E, de Neeling A, van de Sande-Bruinsma N, Beaujean D, et al. Emergence of methicillin-resistant Staphylococcus aureus of animal origin in humans. Emerg Infect Dis. 2007 Dec;13(12):1834-9.

http://dx.doi.org/10.3201/eid1312.070384

Vieira AR, Collignon P, Aarestrup FM, McEwen SA, Hendriksen RS, Hald T, et al. Association between antimicrobial resistance in Escherichia coli isolates from food animals and blood stream isolates from humans in Europe: an ecological study. Foodborne Pathog Dis. 2011 Dec;8(12):1295-301.

http://dx.doi.org/10.1089/fpd.2011.0950

Haeusler GM, Curtis N. Non-typhoidal Salmonella in children: microbiology, epidemiology and treatment. Adv Exp Med Biol. 2013;764:13-26.

http://dx.doi.org/10.1007/978-1-4614-4726-9_2

Endtz HP, Ruijs GJ, van Klingeren B, Jansen WH, van der Reyden T, Mouton RP. Quinolone resistance in campylobacter isolated from man and poultry following the introduction of fluoroquinolones in veterinary medicine. J Antimicrob Chemother. 1991 Feb;27(2):199-208.

http://dx.doi.org/10.1093/jac/27.2.199

MacGregor LH, Cumming GS, Hockey PAR. Understanding pathogen transmission dynamics in waterbird communities: At what scale should interactions be studied? South African Journal of Science. 2011;107(9/10):1-10.

http://dx.doi.org/10.4102/sajs.v107i9/10.283

Spellberg B, Guidos R, Gilbert D, Bradley J, Boucher HW, Scheld WM, et al. The epidemic of antibiotic-resistant infections: a call to action for the medical community from the Infectious Diseases Society of America. Clin Infect Dis. 2008 Jan 15;46(2):155-64.

http://dx.doi.org/10.1086/524891

Baquero F, Negri MC, Morosini MI, Blazquez J. Antibiotic-selective environments. Clin Infect Dis. 1998 Aug;27 Suppl 1:S5-11.

http://dx.doi.org/10.1086/514916

Chander Y, Kumar K, Goyal SM, Gupta SC. Antibacterial activity of soil-bound antibiotics. J Environ Qual. 2005 Nov-Dec;34(6):1952-7.

http://dx.doi.org/10.2134/jeq2005.0017

Kummerer K. Antibiotics in the aquatic environment--a review--part I. Chemosphere. 2009 Apr;75(4):417-34.

http://dx.doi.org/10.1016/j.chemosphere.2008.11.086

Liu A, Fong A, Becket E, Yuan J, Tamae C, Medrano L, et al. Selective advantage of resistant strains at trace levels of antibiotics: a simple and ultrasensitive color test for detection of antibiotics and genotoxic agents. Antimicrob Agents Chemother. 2011 Mar;55(3):1204-10.

http://dx.doi.org/10.1128/AAC.01182-10

Gefen O, Balaban NQ. The importance of being persistent: heterogeneity of bacterial populations under antibiotic stress. FEMS Microbiol Rev. 2009 Jul;33(4):704-17.

http://dx.doi.org/10.1111/j.1574-6976.2008.00156.x

Lewis K. Persister cells, dormancy and infectious disease. Nat Rev Microbiol. 2007 Jan;5(1):48-56.

http://dx.doi.org/10.1038/nrmicro1557

Lewis K. Persister cells. Annu Rev Microbiol. 2010;64:357-72.

http://dx.doi.org/10.1146/annurev.micro.112408.134306

Balaban NQ, Merrin J, Chait R, Kowalik L, Leibler S. Bacterial persistence as a phenotypic switch. Science. 2004 Sep 10;305(5690):1622-5.

http://dx.doi.org/10.1126/science.1099390

Keren I, Kaldalu N, Spoering A, Wang Y, Lewis K. Persister cells and tolerance to antimicrobials. FEMS Microbiol Lett. 2004 Jan 15;230(1):13-8.

http://dx.doi.org/10.1016/S0378-1097(03)00856-5

Shah D, Zhang Z, Khodursky A, Kaldalu N, Kurg K, Lewis K. Persisters: a distinct physiological state of E. coli. BMC Microbiol. 2006;6:53.

http://dx.doi.org/10.1186/1471-2180-6-53

Grenfell BT, Pybus OG, Gog JR, Wood JL, Daly JM, Mumford JA, et al. Unifying the epidemiological and evolutionary dynamics of pathogens. Science. 2004 Jan 16;303(5656):327-32.

http://dx.doi.org/10.1126/science.1090727

Kint CI, Verstraeten N, Fauvart M, Michiels J. New-found fundamentals of bacterial persistence. Trends Microbiol. 2012 Dec;20(12):577-85.

http://dx.doi.org/10.1016/j.tim.2012.08.009

Kiani D, Quinn EL, Burch KH, Madhavan T, Saravolatz LD, Neblett TR. The increasing importance of polymicrobial bacteremia. Jama. 1979 Sep 7;242(10):1044-7.

http://dx.doi.org/10.1001/jama.1979.03300100022015

Fauvart M, De Groote VN, Michiels J. Role of persister cells in chronic infections: clinical relevance and perspectives on anti-persister therapies. J Med Microbiol. 2011 Jun;60(Pt 6):699-709.

http://dx.doi.org/10.1099/jmm.0.030932-0

Kahlmeter G, Brown DF, Goldstein FW, MacGowan AP, Mouton JW, Osterlund A, et al. European harmonization of MIC breakpoints for antimicrobial susceptibility testing of bacteria. J Antimicrob Chemother. 2003 Aug;52(2):145-8.

http://dx.doi.org/10.1093/jac/dkg312

Wormser GP, Schwartz I. Antibiotic treatment of animals infected with Borrelia burgdorferi. Clin Microbiol Rev. 2009 Jul;22(3):387-95.

http://dx.doi.org/10.1128/CMR.00004-09

Barthold SW, Cadavid D, Philipp MT. Animal Models of Borreliosis. In: Samuels DS, Radolf J, editors. Borrelia, Molecular Biology, Host Interaction and Pathogenesis. Norfolk, UK: Caister Academic Press; 2010. p. 353-405.

Embers ME, Barthold SW, Borda JT, Bowers L, Doyle L, Hodzic E, et al. Persistence of Borrelia burgdorferi in rhesus macaques following antibiotic treatment of disseminated infection. PLoS One. 2012;7(1):e29914.

http://dx.doi.org/10.1371/journal.pone.0029914

Hodzic E, Imai D, Feng S, Barthold SW. Resurgence of persisting non-cultivable Borrelia burgdorferi following antibiotic treatment in mice. PLoS One. 2014;9(1):e86907.

http://dx.doi.org/10.1371/journal.pone.0086907

Straubinger RK, Straubinger AF, Harter L, Jacobson RH, Chang YF, Summers BA, et al. Borrelia burgdorferi migrates into joint capsules and causes an up-regulation of interleukin-8 in synovial membranes of dogs experimentally infected with ticks. Infect Immun. 1997 Apr;65(4):1273-85.

Yrjanainen H, Hytonen J, Hartiala P, Oksi J, Viljanen MK. Persistence of borrelial DNA in the joints of Borrelia burgdorferi-infected mice after ceftriaxone treatment. Apmis. 2010 Sep 1;118(9):665-73.

http://dx.doi.org/10.1111/j.1600-0463.2010.02615.x

Breier F, Khanakah G, Stanek G, Kunz G, Aberer E, Schmidt B, et al. Isolation and polymerase chain reaction typing of Borrelia afzelii from a skin lesion in a seronegative patient with generalized ulcerating bullous lichen sclerosus et atrophicus. Br J Dermatol. 2001 Feb;144(2):387-92.

http://dx.doi.org/10.1046/j.1365-2133.2001.04034.x

Honegr K, Hulinska D, Beran J, Dostal V, Havlasova J, Cermakova Z. Long term and repeated electron microscopy and PCR detection of Borrelia burgdorferi sensu lato after an antibiotic treatment. Cent Eur J Public Health. 2004 Mar;12(1):6-11.

Hunfeld KP, Ruzic-Sabljic E, Norris DE, Kraiczy P, Strle F. In vitro susceptibility testing of Borrelia burgdorferi sensu lato isolates cultured from patients with erythema migrans before and after antimicrobial chemotherapy. Antimicrob Agents Chemother. 2005 Apr;49(4):1294-301.

http://dx.doi.org/10.1128/AAC.49.4.1294-1301.2005

Oksi J, Marjamaki M, Nikoskelainen J, Viljanen MK. Borrelia burgdorferi detected by culture and PCR in clinical relapse of disseminated Lyme borreliosis. Ann Med. 1999 Jun;31(3):225-32.

http://dx.doi.org/10.3109/07853899909115982

Priem S, Burmester GR, Kamradt T, Wolbart K, Rittig MG, Krause A. Detection of Borrelia burgdorferi by polymerase chain reaction in synovial membrane, but not in synovial fluid from patients with persisting Lyme arthritis after antibiotic therapy. Ann Rheum Dis. 1998;57(2):118-21.

http://dx.doi.org/10.1136/ard.57.2.118

Barthold SW, Hodzic E, Imai DM, Feng S, Yang X, Luft BJ. Ineffectiveness of tigecycline against persistent Borrelia burgdorferi. Antimicrob Agents Chemother. 2010 Feb;54(2):643-51.

http://dx.doi.org/10.1128/AAC.00788-09

Lewis K. Multidrug tolerance of biofilms and persister cells. Curr Top Microbiol Immunol. 2008;322:107-31.

http://dx.doi.org/10.1007/978-3-540-75418-3_6

Biskup UG, Strle F, Ruzic-Sabljic E. Loss of plasmids of Borrelia burgdorferi sensu lato during prolonged in vitro cultivation. Plasmid. 2011 Oct;66(1):1-6.

http://dx.doi.org/10.1016/j.plasmid.2011.02.006

Schwan TG, Burgdorfer W, Garon CF. Changes in infectivity and plasmid profile of the Lyme disease spirochete, Borrelia burgdorferi, as a result of in vitro cultivation. Infect Immun. 1988;56(8):1831-6.

Allen HK, Donato J, Wang HH, Cloud-Hansen KA, Davies J, Handelsman J. Call of the wild: antibiotic resistance genes in natural environments. Nat Rev Microbiol. 2010 Apr;8(4):251-9.

http://dx.doi.org/10.1038/nrmicro2312

Dolejska M, Cizek A, Literak I. High prevalence of antimicrobial-resistant genes and integrons in Escherichia coli isolates from Black-headed Gulls in the Czech Republic. J Appl Microbiol. 2007 Jul;103(1):11-9.

http://dx.doi.org/10.1111/j.1365-2672.2006.03241.x

Gakuya FM, Kyule MN, Gathura PB, Kariuki S. Antimicrobial susceptibility and plasmids from Escherichia coli isolated from rats. East Afr Med J. 2001 Oct;78(10):518-22.

http://dx.doi.org/10.4314/eamj.v78i10.8960

Gaukler SM, Linz GM, Sherwood JS, Dyer NW, Bleier WJ, Wannemuehler YM, et al. Escherichia coli, Salmonella, and Mycobacterium avium subsp. paratuberculosis in wild European starlings at a Kansas cattle feedlot. Avian diseases. 2009 Dec;53(4):544-51.

http://dx.doi.org/10.1637/8920-050809-Reg.1

Power ML, Emery S, Gillings MR. Into the wild: dissemination of antibiotic resistance determinants via a species recovery program. PLoS One. 2013;8(5):e63017.

http://dx.doi.org/10.1371/journal.pone.0063017

Radhouani H, Silva N, Poeta P, Torres C, Correia S, Igrejas G. Potential impact of antimicrobial resistance in wildlife, environment and human health. Front Microbiol. 2014;5:23.

http://dx.doi.org/10.3389/fmicb.2014.00023

Sherley M, Gordon DM, Collignon PJ. Variations in antibiotic resistance profile in Enterobacteriaceae isolated from wild Australian mammals. Environmental microbiology. 2000 Dec;2(6):620-31.

http://dx.doi.org/10.1046/j.1462-2920.2000.00145.x

Souza V, Rocha M, Valera A, Eguiarte LE. Genetic structure of natural populations of Escherichia coli in wild hosts on different continents. Appl Environ Microbiol. 1999 Aug;65(8):3373-85.

Published
2015-07-08
How to Cite
1.
Hodzic E. Lyme Borreliosis: Is there a preexisting (natural) variation in antimicrobial susceptibility among Borrelia burgdorferi strains?. Bosn J of Basic Med Sci [Internet]. 2015Jul.8 [cited 2019Nov.13];15(3):1-13. Available from: http://bjbms.org/ojs/index.php/bjbms/article/view/594
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Reviews