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

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TLDR
A summation of the different NRP models and a critical analysis of their respective advantages and disadvantages relating to their physiological relevance are provided.
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.

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Journal ArticleDOI

Immune Response to Mycobacterium tuberculosis: A Narrative Review.

TL;DR: This narrative mini-review summarizes the various immunologic mechanisms which modulate the individual ability to fight Mtb infection taking in account the major host and pathogen determinants in the susceptibility to tuberculosis.
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Acetylation of Response Regulator Protein MtrA in M. tuberculosis Regulates Its Repressor Activity.

TL;DR: In this paper, the authors show that MtrA undergoes nonenzymatic acetylation through acetyl phosphate, modulating its activities independent of its phosphorylation status.
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Quinoline heterocyclic containing plant and marine candidates against drug-resistant Mycobacterium tuberculosis: A systematic drug-ability investigation.

TL;DR: In this article , the authors have selected 65 natural quinoline heterocycles bearing potential anti-TB agents (40 plant-derived and 25 marine-derived) within MIC value ≤ 50 μg/mL from an extensive literature search.
Journal ArticleDOI

A Universal Stress Protein That Controls Bacterial Stress Survival in Micrococcus luteus.

TL;DR: A specific universal stress protein (UspA616) controls NRP in Micrococcus luteus and suggests a function for homologous proteins in other bacteria, suggesting Usps are important stress proteins across diverse bacterial species.
Journal ArticleDOI

Targeting the Mycobacterium tuberculosis Stringent Response as a Strategy for Shortening Tuberculosis Treatment.

TL;DR: The stringent response is well conserved across bacterial species and is a key pathway involved both in bacterial survival and virulence and in the induction of antibiotic tolerance in Mycobacteria as discussed by the authors.
References
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Journal ArticleDOI

A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays.

TL;DR: A screening window coefficient, called "Z- factor," is defined, which is reflective of both the assay signal dynamic range and the data variation associated with the signal measurements, and therefore is suitable for assay quality assessment.

Tackling drug-resistant infections globally: final report and recommendations

Jim O'Neill
TL;DR: Suggested reading taken from the last 12 months of the Commission’s weekly publication “On the Radar” highlights papers and reporting exploring the evidence for the effectiveness of antimicrobial stewardship in hospitals, the scope of the problem of antimacterial resistance, and some specific stewardship strategies.
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The taxonomic significance of fermentative versus oxidative metabolism of carbohydrates by various gram negative bacteria

TL;DR: In the absence of compounds such as nitrates, the oxidation of carbohydrates is a strictly aerobic process, whereas fermentation is an anaerobic process.
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Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium.

TL;DR: MABA is sensitive, rapid, inexpensive, and nonradiometric and offers the potential for screening, with or without analytical instrumentation, large numbers of antimicrobial compounds against slow-growing mycobacteria.
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Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling.

TL;DR: A model in which M. tuberculosis arrests growth, decreases its respiration rate and is resistant to isoniazid, rifampicin and metronidazole is established, which is generated a model with which to search for agents active against persistent M.culosis.
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