Preprint Review Version 2 Preserved in Portico This version is not peer-reviewed

Modelling a Silent Epidemic: A Review of the In Vitro Models of Latent Tuberculosis

Version 1 : Received: 29 October 2018 / Approved: 30 October 2018 / Online: 30 October 2018 (04:08:45 CET)
Version 2 : Received: 13 November 2018 / Approved: 14 November 2018 / Online: 14 November 2018 (10:24:31 CET)

A peer-reviewed article of this Preprint also exists.

Gibson, S.E.; Harrison, J.; Cox, J.A. Modelling a Silent Epidemic: A Review of the In Vitro Models of Latent Tuberculosis. Pathogens 2018, 7, 88. Gibson, S.E.; Harrison, J.; Cox, J.A. Modelling a Silent Epidemic: A Review of the In Vitro Models of Latent Tuberculosis. Pathogens 2018, 7, 88.

Abstract

Tuberculosis (TB) is the primary cause of death by a single infectious agent; responsible for around two million deaths in 2016. A major virulence factor of TB is the ability to enter a latent or Non-Replicating Persistent (NRP) state which is presumed untreatable. Approximately, 1.7 billion people are latently infected with TB and on reactivation many of these infections are drug resistant. As the current treatment is ineffective and diagnosis remains poor, millions of people have the potential to reactivate into active TB disease. The immune system seeks to control the TB infection by containing the bacteria in a granuloma, where it is exposed to stressful anaerobic and nutrient deprived conditions. It is thought to be these environmental conditions that trigger the NRP state. A number of in vitro models have been developed that mimic conditions within the granuloma to a lesser or greater extent. These different models have all been utilised for the research of different characteristics of NRP Mycobacterium tuberculosis, however their disparity in approach and physiological relevance often results in inconsistencies and a lack of consensus between studies. This review provides a summation of the different NRP models and a critical analysis of their respective advantages and disadvantages relating to their physiological relevance.

Keywords

tuberculosis; latency; non-replicating persistent; antibiotic; drug discovery; mycobacterium tuberculosis

Subject

Biology and Life Sciences, Immunology and Microbiology

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