Mycobacterium tuberculosis produces several bacterial effectors impacting the colonization of phagocytes. Here, we report that the putative lipoprotein LppM hinders phagocytosis by macrophages in a toll-like receptor 2-dependent manner. Moreover, recombinant LppM is able to functionally complement the phenotype of the mutant, when exogenously added during macrophage infection. LppM is also implicated in the phagosomal maturation, as a lppM deletion mutant is more easily addressed towards the acidified compartments of the macrophage than its isogenic parental strain. In addition, this mutant was affected in its ability to induce the secretion of pro-inflammatory chemokines, interferon-gamma-inducible protein-10, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1α. Thus, our results describe a new mycobacterial protein involved in the early trafficking of the tubercle bacillus and its manipulation of the host immune response.
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http://dx.doi.org/10.1111/cmi.12619 | DOI Listing |
Sci Rep
January 2025
The Jenner Institute, University of Oxford, Oxford, UK.
BCG remains the only licensed vaccine for tuberculosis (TB), but its efficacy wanes over time. Subunit vaccines, aim to improve BCG immunity and protection, by inducing responses to a few mycobacterial antigens delivered with a specific platform. Since the platform shapes the immune response induced, selecting the right platform has been challenging due to the lack of immune correlates of protection.
View Article and Find Full Text PDFPLoS Med
January 2025
Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
Background: Globally, over one-third of pulmonary tuberculosis (TB) disease diagnoses are made based on clinical criteria after a negative bacteriological test result. There is limited information on the factors that determine clinicians' decisions to initiate TB treatment when initial bacteriological test results are negative.
Methods And Findings: We performed a systematic review and individual patient data meta-analysis using studies conducted between January 2010 and December 2022 (PROSPERO: CRD42022287613).
PLoS One
January 2025
Department of Medical Microbiology and Immunology, University of Nairobi, Nairobi, Kenya.
The lung environment harbours a community of microbes that play a significant role in health and disease, including innate protection against pathogenic microorganisms. Infection with Mycobacterium tuberculosis, psychological stress associated with the tuberculosis (TB) disease, and the metabolites from the rifampicin treatment regimen have been reported to induce hyperglycemia and consequently type 2 diabetes mellitus (T2DM) in individuals not previously diabetic. The high glucose concentration is proposed to alter the composition of the lung microbiota and airway homeostasis, exerting an influence on TB disease and treatment outcomes.
View Article and Find Full Text PDFJ 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.
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