Resurgence of persisting non-cultivable Borrelia burgdorferi following antibiotic treatment in mice.

The agent of Lyme borreliosis, Borrelia burgdorferi, evades host immunity and establishes persistent infections in its varied mammalian hosts. This persistent biology may pose challenges to effective antibiotic treatment. Experimental studies in dogs, mice, and non-human primates have found persiste...

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Autores principales:	Emir Hodzic, Denise Imai, Sunlian Feng, Stephen W Barthold
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1a832496e43d4b44ac6501bc2fc9a9ba
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spelling	oai:doaj.org-article:1a832496e43d4b44ac6501bc2fc9a9ba2021-11-18T08:36:01ZResurgence of persisting non-cultivable Borrelia burgdorferi following antibiotic treatment in mice.1932-620310.1371/journal.pone.0086907https://doaj.org/article/1a832496e43d4b44ac6501bc2fc9a9ba2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24466286/?tool=EBIhttps://doaj.org/toc/1932-6203The agent of Lyme borreliosis, Borrelia burgdorferi, evades host immunity and establishes persistent infections in its varied mammalian hosts. This persistent biology may pose challenges to effective antibiotic treatment. Experimental studies in dogs, mice, and non-human primates have found persistence of B. burgdorferi DNA following treatment with a variety of antibiotics, but persisting spirochetes are non-cultivable. Persistence of B. burgdorferi DNA has been documented in humans following treatment, but the significance remains unknown. The present study utilized a ceftriaxone treatment regimen in the C3H mouse model that resulted in persistence of non-cultivable B. burgdorferi in order to determine their long-term fate, and to examine their effects on the host. Results confirmed previous studies, in which B. burgdorferi could not be cultured from tissues, but low copy numbers of B. burgdorferi flaB DNA were detectable in tissues at 2, 4 and 8 months after completion of treatment, and the rate of PCR-positive tissues appeared to progressively decline over time. However, there was resurgence of spirochete flaB DNA in multiple tissues at 12 months, with flaB DNA copy levels nearly equivalent to those found in saline-treated mice. Despite the continued non-cultivable state, RNA transcription of multiple B. burgdorferi genes was detected in host tissues, flaB DNA was acquired by xenodiagnostic ticks, and spirochetal forms could be visualized within ticks and mouse tissues by immunofluorescence and immunohistochemistry, respectively. A number of host cytokines were up- or down-regulated in tissues of both saline- and antibiotic-treated mice in the absence of histopathology, indicating host response to the presence of non-cultivable, despite the lack of inflammation in tissues.Emir HodzicDenise ImaiSunlian FengStephen W BartholdPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e86907 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emir Hodzic Denise Imai Sunlian Feng Stephen W Barthold Resurgence of persisting non-cultivable Borrelia burgdorferi following antibiotic treatment in mice.
description	The agent of Lyme borreliosis, Borrelia burgdorferi, evades host immunity and establishes persistent infections in its varied mammalian hosts. This persistent biology may pose challenges to effective antibiotic treatment. Experimental studies in dogs, mice, and non-human primates have found persistence of B. burgdorferi DNA following treatment with a variety of antibiotics, but persisting spirochetes are non-cultivable. Persistence of B. burgdorferi DNA has been documented in humans following treatment, but the significance remains unknown. The present study utilized a ceftriaxone treatment regimen in the C3H mouse model that resulted in persistence of non-cultivable B. burgdorferi in order to determine their long-term fate, and to examine their effects on the host. Results confirmed previous studies, in which B. burgdorferi could not be cultured from tissues, but low copy numbers of B. burgdorferi flaB DNA were detectable in tissues at 2, 4 and 8 months after completion of treatment, and the rate of PCR-positive tissues appeared to progressively decline over time. However, there was resurgence of spirochete flaB DNA in multiple tissues at 12 months, with flaB DNA copy levels nearly equivalent to those found in saline-treated mice. Despite the continued non-cultivable state, RNA transcription of multiple B. burgdorferi genes was detected in host tissues, flaB DNA was acquired by xenodiagnostic ticks, and spirochetal forms could be visualized within ticks and mouse tissues by immunofluorescence and immunohistochemistry, respectively. A number of host cytokines were up- or down-regulated in tissues of both saline- and antibiotic-treated mice in the absence of histopathology, indicating host response to the presence of non-cultivable, despite the lack of inflammation in tissues.
format	article
author	Emir Hodzic Denise Imai Sunlian Feng Stephen W Barthold
author_facet	Emir Hodzic Denise Imai Sunlian Feng Stephen W Barthold
author_sort	Emir Hodzic
title	Resurgence of persisting non-cultivable Borrelia burgdorferi following antibiotic treatment in mice.
title_short	Resurgence of persisting non-cultivable Borrelia burgdorferi following antibiotic treatment in mice.
title_full	Resurgence of persisting non-cultivable Borrelia burgdorferi following antibiotic treatment in mice.
title_fullStr	Resurgence of persisting non-cultivable Borrelia burgdorferi following antibiotic treatment in mice.
title_full_unstemmed	Resurgence of persisting non-cultivable Borrelia burgdorferi following antibiotic treatment in mice.
title_sort	resurgence of persisting non-cultivable borrelia burgdorferi following antibiotic treatment in mice.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/1a832496e43d4b44ac6501bc2fc9a9ba
work_keys_str_mv	AT emirhodzic resurgenceofpersistingnoncultivableborreliaburgdorferifollowingantibiotictreatmentinmice AT deniseimai resurgenceofpersistingnoncultivableborreliaburgdorferifollowingantibiotictreatmentinmice AT sunlianfeng resurgenceofpersistingnoncultivableborreliaburgdorferifollowingantibiotictreatmentinmice AT stephenwbarthold resurgenceofpersistingnoncultivableborreliaburgdorferifollowingantibiotictreatmentinmice
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Resurgence of persisting non-cultivable Borrelia burgdorferi following antibiotic treatment in mice.

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