Anaerobic adaptation of Mycobacterium avium subspecies paratuberculosis in vitro: similarities to M. tuberculosis and differential susceptibility to antibiotics

Parrish, Nicole; Vadlamudi, Aravinda; Goldberg, Neil

doi:10.1186/s13099-017-0183-z

Cited by 6 publications

(4 citation statements)

References 43 publications

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“…These experimental data have been validated by the negativity of the negative controls along with congruent conclusions achieved by three experimental approaches. With respect to its phylogenetic position among mycobacteria, the fact that M. ulcerans exhibited dormancy was not entirely surprising: dormancy has already been reported for Mycobacterium tuberculosis [13], Mycobacterium bovis BCG [16], Mycobacterium smegmatis [17] and Mycobacterium avium subspecies paratuberculosis [18]. In this study, microcalorimetry was used for the first time to investigate the physiology of M. ulcerans .…”

Section: Discussionmentioning

confidence: 87%

Experimental pieces of evidence forMycobacterium ulceransdormancy

Drancourt

Loukil

Lalaoui

et al. 2020

Preprint

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BackgroundWhether Mycobacterium ulcerans, the etiological agent of the neglected Buruli ulcer in numerous tropical countries, would exist in a dormant state as reported for closely related Mycobacterium species, is not established.MethodologySix M. ulcerans strains were exposed to a progressive depletion in oxygen for two months, using a previously described Wayne model of dormancy; and further examined by microscopy using DDD staining, microcalorimetry and subculture in the presence of dead and replicative M. ulcerans as controls.Principal Findings/ConclusionsM. ulcerans CU001 strain died during the progressive oxygen depletion and four of five remaining strains exhibited Nile Red-stained intracellular lipid droplets after DDD staining and a 14-20-day regrowth when exposed to ambient air, diagnosing dormancy. A fifth M. ulcerans 19423 strain stained negative in DDD and slowly regrew in 27 days. Three tested M. ulcerans strains yielded microcalorimetric pattern similar to that of the negative (dead) homologous controls, differing from that of the homologous positive (replicative) controls. The relevance of these experimental observations, suggesting a previously unreported dormancy state of M. ulcerans, needs to be investigated in the natural ecological niches where M. ulcerans thrive and in Buruli ulcer lesions.Author summaryMycobacterium ulcerans is an environmental opportunistic pathogen of mammals and humans, causing a subcutaneous necrotizing infection named Buruli ulcer. Molecular detection of M. ulcerans DNA revealed different ecological niches where M. ulcerans may thrive, but the molecular biology approach does not catch the physiological state of M. ulcerans in these different ecological niches. Thus, the reservoir and the mode of transmission of M. ulcerans remain elusive. Here, we investigated experimental dormancy of M. ulcerans by using a previously described Wayne model of dormancy coupled with microscopy using DDD staining, microcalorimetry and subculture. Our findings demonstrate for the first time that some M. ulcerans strains exhibit a physiological state of dormancy; potentially limiting isolation and culture of M. ulcerans from environmental niches.

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Section: Discussionmentioning

confidence: 87%

Experimental pieces of evidence forMycobacterium ulceransdormancy

Drancourt

Loukil

Lalaoui

et al. 2020

Preprint

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“…With respect to its phylogenetic position among mycobacteria, the fact that M. ulcerans exhibited dormancy was not entirely surprising: dormancy has already been reported for M. tuberculosis, 13 M. bovis BCG, 16 M smegmatis, and M. avium subspecies paratuberculosis. 17,18 In this study, microcalorimetry was used for the first time to investigate the physiology of M. ulcerans. Indeed, microcalorimetry had been previously used in determining the minimum inhibitory concentration of isoniazid, ethambutol, and moxifloxacin against M. smegmatis, M. avium, and M. tuberculosis, 19 but never incorporated M. ulcerans, to our knowledge.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium ulcerans Experimental Dormancy

Loukil

Lalaoui

Bogreau

et al. 2022

The American Journal of Tropical Medicine and Hygiene

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Whether Mycobacterium ulcerans, the etiological agent of Buruli ulcer in numerous tropical countries, would exist in a dormant state as reported for closely related Mycobacterium species, has not been established. Six M. ulcerans strains were exposed to a progressive depletion in oxygen for 2 months, using the Wayne model of dormancy previously described for M. tuberculosis, and further examined by microscopy after staining of dynamic, dormant, and dead mycobacteria (DDD staining), microcalorimetry and subculture in the presence of dead and replicative M. ulcerans as controls. Mycobacterium ulcerans CU001 strain died during the progressive oxygen depletion and four of five remaining strains exhibited Nile red–stained intracellular lipid droplets and a 14- to 20-day regrowth when exposed to ambient air, consistent with dormancy. A fifth M. ulcerans 19423 strain stained negative in DDD staining and slowly regrew in 27 days. Three tested M. ulcerans strains yielded microcalorimetric pattern similar to that of the negative (dead) homologous controls, differing from that of the homologous positive (replicative) controls. The relevance of these experimental observations, suggesting a previously unreported dormancy state of M. ulcerans, warrants further investigations in the natural ecological niches where M. ulcerans thrive as well as in Buruli ulcer lesions.

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“…This could affect vaccine targets. As an example, mycobacteria can metabolise both aerobically and anaerobically depending on environmental conditions [74]. Similar distinctions may impact on effective vaccination, particularly where living vaccines such as BCG are given.…”

Section: Vaccinationmentioning

confidence: 99%

Mycobacterium avium ssp. paratuberculosis and Crohn’s Disease—Diagnostic Microbiological Investigations Can Inform New Therapeutic Approaches

Aitken,

Agrawal

2024

Antibiotics

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Mycobacterium avium ssp. paratuberculosis (MAP) is the cause of Johne’s disease (JD), which is a chronic infectious gastrointestinal disease of ruminants and is often fatal. In humans, MAP has been associated with Crohn’s disease (CD) for over a century, without conclusive evidence of pathogenicity. Numerous researchers have contributed to the subject, but there is still a need for evidence of the causation of CD by MAP. An infectious aetiology in CD that is attributable to MAP can only be proven by bacteriological investigations. There is an urgency in resolving this question due to the rising global incidence rates of CD. Recent papers have indicated the “therapeutic ceiling” may be close in the development of new biologics. Clinical trial outcomes have demonstrated mild or inconsistent improvements in therapeutic interventions over the last decades when compared with placebo. The necessity to revisit therapeutic options for CD is becoming more urgent and a renewed focus on causation is essential for progress in identifying new treatment options. This manuscript discusses newer interventions, such as vaccination, FMT, dietary remediation and gut microbiome regulation, that will become more relevant as existing therapeutic options expire. Revisiting the MAP theory as a potential infectious cause of CD, rather than the prevailing concept of an “aberrant immune response” will require expanding the current therapeutic programme to include potential new alternatives, and combinations of existing treatments. To advance research on MAP in humans, it is essential for microbiologists and medical scientists to microscopically detect CWDM and to biologically amplify the growth by directed culture.

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Anaerobic adaptation of Mycobacterium avium subspecies paratuberculosis in vitro: similarities to M. tuberculosis and differential susceptibility to antibiotics

Cited by 6 publications

References 43 publications

Experimental pieces of evidence forMycobacterium ulceransdormancy

Experimental pieces of evidence forMycobacterium ulceransdormancy

Mycobacterium ulcerans Experimental Dormancy

Mycobacterium avium ssp. paratuberculosis and Crohn’s Disease—Diagnostic Microbiological Investigations Can Inform New Therapeutic Approaches

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