Abstract
BackgroundMycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne’s disease in ruminants and is associated with Crohn’s disease (CD) in humans, although the latter remains controversial. In this study, we investigated the ability of MAP to adapt to anaerobic growth using the “Wayne” model of non-replicating persistence (NRP) developed for M. tuberculosis.ResultsAll strains adapted to anaerobiosis over time in a manner similar to that seen with MTB. Susceptibility to 12 antibiotics varied widely between strains under aerobic conditions. Under anaerobic conditions, no drugs caused significant growth inhibition (>0.5 log) except metronidazole, resulting in an average decrease of ~2 logs.ConclusionsThese results demonstrate that MAP is capable of adaptation to NRP similar to that observed for MTB with differential susceptibility to antibiotics under aerobic versus anaerobic conditions. Such findings have significant implications for our understanding of the pathogenesis of MAP in vivo and the treatment of CD should this organism be established as the causative agent.
Highlights
Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne’s disease in ruminants and is associated with Crohn’s disease (CD) in humans, the latter remains controversial
The goal of this study was aimed at answering two specific questions related to the biology of MAP: (1) this fastidious species is known to grow under aerobic conditions so long as culture medium is supplemented with Mycobactin J; can MAP adapt to a ‘latent’ or non-replicating, persistent state in vitro as is the case with M. tuberculosis and BCG and, (2) if so, what is the susceptibility of MAP to antimycobacterial drugs under aerobic versus anaerobic conditions?
The results from this study demonstrate that MAP is capable of both aerobic growth and adaptation in anaerobiosis when using the ‘Wayne’ in vitro model developed for M. tuberculosis
Summary
Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne’s disease in ruminants and is associated with Crohn’s disease (CD) in humans, the latter remains controversial. The etiology of CD is unknown, the clinical findings in humans resemble those of Johne’s disease (JD) in cattle, caused by Mycobacterium avium subspecies paratuberculosis (MAP) [1]. MAP as the causative agent of CD has been met with both support and skepticism despite the similarities to JD [3]. Skepticism of MAP as the causative agent of CD stems from several lines of evidence which support a strong role for immune dysregulation and highlight failure to achieve a cure with antimicrobial therapy [1, 16]. Antimicrobial regimens for treatment of CD have included antibiotics such as rifaximin (RFX), ciprofloxacin (CIP), and metronidazole (MET) given separately or in combination
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