Structural and DNA Binding Properties of Mycobacterial Integration Host Factor mIHF
Publication date: Available online 14 December 2019Source: Journal of Structural BiologyAuthor(s): Nina T. Odermatt, Moreno Lelli, Torsten Herrmann, Luciano A. Abriata, Aleksandre Japaridze, Hubert Voilquin, Rajkumar Singh, Jérémie Piton, Lyndon Emsley, Giovanni Dietler, Stewart T. ColeAbstractIn bacteria, nucleoid associated proteins (NAPs) take part in active chromosome organization by supercoil management, three-dimensional DNA looping and direct transcriptional control. Mycobacterial integration host factor (mIHF, rv1388) is a NAP restricted to Actinobacteria and essential for survival of the human pathogen Mycobacterium tuberculosis. We show in vitro that DNA binding by mIHF strongly stabilizes the protein and increases its melting temperature. The structure obtained by Nuclear Magnetic Resonance (NMR) spectroscopy characterizes mIHF as a globular protein with a protruding alpha helix and a disordered N-terminus, similar to Streptomyces coelicolor IHF (sIHF). NMR revealed no residues of high flexibility, suggesting that mIHF is a rigid protein overall that does not undergo structural rearrangements. We show that mIHF only binds to double stranded DNA in solution, through two DNA binding sites (DBSs) similar to those identified in the x-ray structure of sIHF. According to Atomic Force Microscopy, mIHF is able to introduce left-handed loops of ca. 100 nm size (∼300 bp) in supercoiled cosmids, thereby unwinding and relaxing the DNA.
CONCLUSION: A high-quality child-friendly FDC water-dispersible tablet was developed improving the treatment of TB in pediatric. PMID: 31944867 [PubMed - as supplied by publisher]
We report two cases of unilateral iris granulomata in two young patients who presented with decreased vision and redness and were found to have well-circumscribed iris granulomas. Both underwent systemic evaluation and had a negative Mantoux test. Biopsy pathology of the lesions revealed granulomatous inflammation but were negative for PCR, staining, and culture for TB. One patient turned out to have multiple pulmonary lesions. The ocular condition initially worsened with steroid therapy alone and improved and resolved completely after starting a 9 months course of anti-tubercular therapy (ATT). PMID: 31944133 [PubMed ...
Publication date: January 2020Source: Journal of Comparative Pathology, Volume 174Author(s): C. López Figueroa, L. Feo Bernabe, M. Martin, E. Vidal, B. Pérez de Val, A. Ramis
Program aims to raise awareness and reduce stigma of TB among young people in India, as part of Johnson&Johnson ’s 10-year initiative to combat world’s leading infectious disease killer
Macrophages are highly plastic cells with critical roles in immunity, cancer, and tissue homeostasis, but how these distinct cellular fates are triggered by environmental cues is poorly understood. To uncover how primary murine macrophages respond to bacterial pathogens, we globally assessed changes in post-translational modifications of proteins during infection with Mycobacterium tuberculosis, a notorious intracellular pathogen. We identified hundreds of dynamically regulated phosphorylation and ubiquitylation sites, indicating that dramatic remodeling of multiple host pathways, both expected and unexpected, occurred dur...
Conclusion: The diagnostic formula developed in the present study can help physicians to differentiate tuberculous meningitis from bacterial meningitis in high-tuberculosis-incidence-areas, particularly in settings with limited microbiological and radiological resources.
Conclusion: The combined picture of 'low IPT initiation and high completion' seen in our study mirrors findings from other countries. Drug stock-out was the key challenge, which obliged health-care providers to prioritize 'IPT completion' over 'IPT initiation'. There is an urgent need to improve the procurement and supply chain management of isoniazid. PMID: 31937200 [PubMed - in process]
Contributors : Siyuan Feng ; Guobao TianSeries Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencingOrganism : Mycolicibacterium smegmatis MC2 155To understand how GreA may affect gene expression at the transcriptional level, we performed whole-transcriptome RNA-seq analyses.To examine whether GreA binds to specific chromosomal regions, we performed chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) and then sought to verify the binding mode of GreA. ChIP-seq experiments were performed by using M. smegmatis strains producing GreA prote...
More than three years after being passed in the legislature, a new law that governs public health in Nunavut is in effect.
We present an alternative, societal framework for economic evaluations that encompasses a broader set of socioeconomic benefits in addition to health benefits. Quantifying a more comprehensive taxonomy of PCV’s benefits will help to address potential undervaluation and may be sufficient not only to justify recommendation and reimbursement but also to stimulate efforts and investment toward closing coverage gaps.