Mycobacterium tuberculosis Transcriptional Adaptation, Growth Arrest and Dormancy Phenotype Development Is Triggered by Vitamin C

BACKGROUND: Tubercle bacilli are thought to persist in a dormant state during latent tuberculosis (TB) infection. Although little is known about the host factors that induce and maintain Mycobacterium tuberculosis (M. tb) within latent lesions, O(2) depletion, nutrient limitation and acidification are some of the stresses implicated in bacterial dormancy development/growth arrest. Adaptation to hypoxia and exposure to NO/CO is implemented through the DevRS/DosT two-component system which induces the dormancy regulon. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that vitamin C (ascorbic acid/AA) can serve as an additional signal to induce the DevR regulon. Physiological levels of AA scavenge O(2) and rapidly induce the DevR regulon at an estimated O(2) saturation of <30%. The kinetics and magnitude of the response suggests an initial involvement of DosT and a sustained DevS-mediated response during bacterial adaptation to increasing hypoxia. In addition to inducing DevR regulon mechanisms, vitamin C induces the expression of selected genes previously shown to be responsive to low pH and oxidative stress, triggers bacterial growth arrest and promotes dormancy phenotype development in M. tb grown in axenic culture and intracellularly in THP-1 cells. CONCLUSIONS/SIGNIFICANCE: Vitamin C mimics multiple intracellular stresses and has wide-ranging regulatory effects on gene expression and physiology of M. tb which leads to growth arrest and a 'dormant' drug-tolerant phenotype, but in a manner independent of the DevRS/DosT system. The 'AA-dormancy infection model' offers a potential alternative to other models of non-replicating persistence of M. tb and may be useful for investigating host-'dormant' M. tb interactions. Our findings offer a new perspective on the role of nutritional factors in TB and suggest a possible role for vitamin C in TB

AgeXtend-SupplementaryandAdditionalData

&lt;p&gt;Supplementary tables, additional data on the training datasets, and the testing data for yeast chronological assay for AgeXtend can be found here.&lt;/p&gt

A case report of recurrent hypokalaemic periodic paralysis in a young male patient

A 21-year-old normotensive male patient presented with acute-onset flaccid paralysis with the history of a similar episode a few months back. Clinical and laboratory evaluation revealed lower motor neuron type of flaccid quadriparesis with hypokalaemia, normal anion gap metabolic acidosis, bicarbonaturia and transtubular potassium concentration gradient more than 7. Subsequently, urine acidification test (by ammonium chloride challenge test) was performed and diagnosis of renal tubular acidosis was established. The patient ultrasound did not show nephrocalcinosis, and history of recurrent diarrhoea preceding the attack revealed that the patient also had coeliac disease. The patient responded to conservative management (Sohl′s solution) and gluten-free diet

A case report of distal RTA presenting as hypokalaemic periodic paralysis in young male

A 21-year-old normotensive male presented with acute onset flaccid paralysis with the history of a similar episode a few months back. Clinical and laboratory evaluation revealed lower motor neuron type of flaccid quadriparesis with hypokalaemia, normal anion gap metabolic acidosis, bicarbonaturia, and transtubular potassium concentration gradient (TTKG) more than 7. Subsequently urine acidification test (by NH4CI challenge test) was done and diagnosis of distal renal tubular acidosis was established. The patient responded to conservative management (Sohl′s solution)

A case report of primary Hodgkin′s disease of bone marrow

Hodgkin′s disease (HD) is a malignant neoplasm of the lymphoid tissues. It arises almost invariably in a single node or chain of nodes. Extranodal disease can be primary or can result from the spread of primary nodal disease to these sites. Primary bone marrow HD is very rare. Here, we present the case of an elderly male, who presented with primary HD of bone marrow

Gauging the impact of a pandemic on the lives and livelihoods of female domestic worker across Indian cities

Domestic workers are one of the most unprotected groups of the global workforce in informal employment who remain outside the ambit of social security and legal protection. Despite their significant contribution to the economy and society, they are often invisible and undervalued. The pre-existing adversities and vulnerabilities became all the more evident during the recent health crisis. While different groups of workers faced constraints to support their livelihood, the women domestic workers were hardest hit, facing total or near unemployment, job losses and economic distress. This paper attempts to analyse the impact of pandemic on the lives and livelihoods of female domestic workers in five Indian cities including Pune, Lucknow, Jhansi, Katni and Bhopal. The analytical findings from the random sample survey of 250 female domestic worker provides a temporal analysis of the impact of covid-19 on the nature of work, income, expenditure and consumption across the various cities of India. Our findings not only increase our understanding on the impact of the crisis for domestic worker but also informal workers in general.&nbsp