(), a rod-shaped acid-fast bacterium, is the causative agent of tuberculosis (TB). TB remains one of the leading causes of morbidity and mortality worldwide. Additionally, approximately one-third of the world's population has latent tuberculosis infection (LTBI) as a result of the body's primary mechanism of defense against infection, the formation of a granuloma. A granuloma is the aggregation of immune cells that encapsulate the bacteria to keep them localized to prevent further infection and thus the bacteria become quiescent. However, if an individual becomes immunocompromised, they become more susceptible to , which may lead to bacterial reactivation and an active infection, because the host is no longer able to generate adequate immune responses. In this study, we examined liposomal glutathione's (L-GSH) effectiveness in promoting the formation of solid, stable granulomas. We assessed this ability by generating in vitro human granulomas constructed from peripheral blood mononuclear cells (PBMCs) that were derived from healthy subjects and testing their granulomatous effector responses against both bacille Calmette-Guérin (BCG) and the highly virulent Erdman strain of . Additionally, we measured the survival and immune characteristics of the Erdman strain of in THP-1 originated macrophages as well as in vitro granulomas generated from individuals from type 2 diabetes (T2DM). Our results demonstrate that L-GSH treatment can decrease the intracellular survival of both BCG and virulent , as well as downregulate the levels of overexpressed proinflammatory cytokines delegated from the granulomas derived from not only healthy subjects but also individuals with T2DM.
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http://dx.doi.org/10.3390/jcm7030040 | DOI Listing |
J Spinal Cord Med
January 2025
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Context: This study aimed to investigate the characteristics, diagnosis, and management of tuberculous longitudinally extensive transverse myelitis (TB-LETM), a rare manifestation of tuberculosis.
Findings: We analyzed two rare cases of TB-LETM and discussed their clinical manifestations and imaging findings in the context of the relevant literature. Patient 1, a 23-year-old female, presented with quadriplegia and dysuria, and spinal magnetic resonance imaging (MRI) revealed lesions extending from C1 to T3.
( ) is the world's most deadly infectious pathogen and new drugs are urgently required to combat the emergence of multi-(MDR) and extensively-(XDR) drug resistant strains. The bacterium specifically upregulates sterol uptake pathways in infected macrophages and the metabolism of host-derived cholesterol is essential for long-term survival Here, we report the development of antitubercular small molecules that inhibit the cholesterol oxidases CYP125 and CYP142, which catalyze the initial step of cholesterol metabolism. An efficient biophysical fragment screen was used to characterize the structure-activity relationships of CYP125 and CYP142, and identify a non-azole small molecule that can bind to the heme cofactor of both enzymes.
View Article and Find Full Text PDFTuberculosis (TB) is historically the world's deadliest infectious disease. New TB drugs that can avoid pre-existing resistance are desperately needed. The β-lactams are the oldest and most widely used class of antibiotics to treat bacterial infections but, for a variety of reasons, they were largely ignored until recently as a potential treatment option for TB.
View Article and Find Full Text PDFThe recalcitrance of to antibiotic treatment has been broadly attributed to the impermeability of the organism's outer mycomembrane. However, the studies that support this inference have been indirect and/or reliant on bulk population measurements. We previously developed the P eptidoglycan A ccessibility C lick- M ediated A ssessme N t (PAC-MAN) method to covalently trap azide-modified small molecules in the peptidoglycan cell wall of live mycobacteria, after they have traversed the mycomembrane.
View Article and Find Full Text PDFOccup Ther Int
January 2025
Occupational Therapy Department, University of the Western Cape, Cape Town, South Africa.
Individuals diagnosed with tuberculosis (TB) and multidrug-resistant (MDR) TB may struggle to return to work after they have completed a rehabilitation program. Multidrug-resistant tuberculosis (MDRTB) has been seen as a condition that is resistant to treatment, hence causing individuals to be economically in-active for considerable periods of time. The aim of the current study was to explore the views of individuals living with MDRTB, individuals with TB, and health professionals treating individuals with TB and MDRTB about the development of a vocational rehabilitation program.
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