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Your search keyword '"Nguyen H. Phu"' showing total 2 results
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2 results on '"Nguyen H. Phu"'

1. Variations in Antimicrobial Activities of Human Monocyte-Derived Macrophage and Their Associations With Tuberculosis Clinical Manifestations

Author

Trinh T. B. Tram, Vu T. N. Ha, Do D. A. Thu, Tran D. Dinh, Hoang N. Nhung, Nguyen T. Hanh, Nguyen H. Phu, Guy E. Thwaites, and Nguyen T. T. Thuong

Subjects
tuberculosis, acidification, proteolysis, human macrophage, variation, Microbiology, QR1-502
Abstract

Macrophages play a significant role in preventing infection through antimicrobial activities, particularly acidification, and proteolysis. Mycobacterium tuberculosis (Mtb) infection can lead to diverse outcomes, from latent asymptomatic infection to active disease involving multiple organs. Monocyte-derived macrophage is one of the main cell types accumulating in lungs following Mtb infection. The variation of intracellular activities of monocyte-derived macrophages in humans and the influence of these activities on the tuberculosis (TB) spectrum are not well understood. By exploiting ligand-specific bead-based assays, we investigated macrophage antimicrobial activities real-time in healthy volunteers (n = 53) with 35 cases of latent TB (LTB), and those with active TB (ATB), and either pulmonary TB (PTB, n = 70) or TB meningitis (TBM, n = 77). We found wide person-to-person variations in acidification and proteolytic activities in response to both non-immunogenic IgG and pathogenic ligands comprising trehalose 6,6'−dimycolate (TDM) from Mtb or β-glucan from Saccharamyces cerevisiase. The variation in the macrophage activities remained similar regardless of stimuli; however, IgG induced stronger acidification activity than immunogenic ligands TDM (P = 10−5, 3 × 10−5 and 0.01 at 30, 60, and 90 min) and β-glucan (P = 10−4, 3 × 10−4 and 0.04 at 30, 60, and 90 min). Variation in proteolysis activity was slightly higher in LTB than in ATB (CV = 40% in LTB vs. 29% in ATB, P = 0.03). There was no difference in measured antimicrobial activities in response to TDM and bacterial killing in macrophages from LTB and ATB, or from PTB and TBM. Our results indicate that antimicrobial activities of monocyte-derived macrophages vary among individuals and show immunological dependence, but suggest these activities cannot be solely responsible for the control of bacterial replication or dissemination in TB.

Published
2020
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2. Influence of stress and antibiotic resistance on cell-length distribution in Mycobacterium tuberculosis clinical isolates

Author

Srinivasan Vijay, Dao N. Vinh, Hoang T. Hai, Vu T. N. Ha, Vu T. M. Dung, Tran D. Dinh, Hoang N. Nhung, Trinh T. B. Tram, Bree B. Aldridge, Nguyen T. Hanh, Do D. A. Thu, Nguyen H. Phu, Guy E. Thwaites, and Nguyen T. T. Thuong

Subjects
0301 basic medicine, Microbiology (medical), Tuberculosis, Multidrug tolerance, medicine.drug_class, 030106 microbiology, Antibiotics, lcsh:QR1-502, Drug resistance, rifampicin, Microbiology, lcsh:Microbiology, Mycobacterium tuberculosis, 03 medical and health sciences, iron deficiency, Antibiotic resistance, multidrug resistance, medicine, oxidative stress, Original Research, biology, macrophage infection, sputum, medicine.disease, biology.organism_classification, 3. Good health, Multiple drug resistance, Immunology, cell-length variation, Rifampicin, medicine.drug
Abstract

Mycobacterial cellular variations in growth and division increase heterogeneity in cell length, possibly contributing to cell-to-cell variation in host and antibiotic stress tolerance. This may be one of the factors influencing Mycobacterium tuberculosis persistence to antibiotics. Tuberculosis is a major public health problem in developing countries, antibiotic persistence and emergence of antibiotic resistance further complicates this problem. We wanted to investigate the factors influencing cell length distribution in clinical M. tuberculosis strains. In parallel we examined M. tuberculosis cell length distribution in a large set of clinical strains (n = 158) from ex-vivo sputum samples, in-vitro macrophage models, and in-vitro cultures. Our aim was to understand the influence of clinically relevant factors such as host stresses, M. tuberculosis lineages, antibiotic resistance, antibiotic concentrations and disease severity on the cell size distribution in clinical M. tuberculosis strains. Increased cell size and cell-to-cell variation in cell length were associated with bacteria in sputum and infected macrophages rather than liquid culture. Multidrug resistant (MDR) strains displayed increased cell length heterogeneity compared to sensitive strains in infected macrophages and also during growth under rifampicin treatment. Importantly, increased cell length was also associated with pulmonary tuberculosis disease severity. Supporting these findings, individual host stresses, such as oxidative stress and iron deficiency, increased cell length heterogeneity of M. tuberculosis strains. In addition we also observed synergism between host stress and rifampicin treatment in increasing cell length in MDR-TB strains. This study has identified the important clinical factors contributing to cell length heterogeneity in clinical M. tuberculosis strains. The role of these cellular adaptations to host and antibiotic tolerance needs further investigation.

Published
2017
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