scholarly journals Survival and Replication of Clinical Mycobacterium tuberculosis Isolates in the Context of Human Innate Immunity

2005 ◽  
Vol 73 (5) ◽  
pp. 2595-2601 ◽  
Author(s):  
Ernestas Janulionis ◽  
Carolina Sofer ◽  
Stephan K. Schwander ◽  
Denarra Nevels ◽  
Barry Kreiswirth ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Mycobacterium Tuberculosis ◽  
Blood Culture ◽  
Whole Blood ◽  
Host Response ◽  
Host Cells ◽  
Clinical Isolates ◽  
The Face ◽  
Mycobacterial Growth ◽  
Reference Strains

ABSTRACT The initial host response to Mycobacterium tuberculosis is driven by innate immunity. For this study, we examined the ability of 18 recent clinical isolates and 5 reference strains to survive and replicate in the context of host innate immunity by using whole blood culture. Six healthy tuberculin-negative volunteers served as subjects. H37Ra showed the least capacity to replicate of any of the strains tested, decreasing in viability 1.3 log CFU during 72 h of whole blood culture, whereas H37Rv increased 0.32 log. Clinical isolates varied greatly in their ability to replicate in blood cells, ranging from −0.4 to +0.8 log (P < 0.001). Four showed significantly more growth than H37Rv, and one showed significantly reduced growth. Host mechanisms for restricting intracellular mycobacterial growth were more effective during the first 24 h of whole blood culture than during the 24- to 72-h period. Certain mycobacterial isolates appeared preferentially able to withstand host defenses during each of these intervals. Although there was relatively more homogeneity among subjects than among strains, one of the six subjects showed a reduced capacity to restrict intracellular mycobacterial growth due to a defect expressed during the first 24 h of culture. Our findings indicate substantial variability in the capacity of clinical tuberculosis isolates to replicate in host cells in the face of innate host immunity.

scholarly journals Application of a whole blood mycobacterial growth inhibition assay to study immunity against Mycobacterium tuberculosis in a high tuberculosis burden population

PLoS ONE ◽  
2017 ◽  
Vol 12 (9) ◽  
pp. e0184563 ◽  
Author(s):  
Richard Baguma ◽  
Adam Penn-Nicholson ◽  
Erica Smit ◽  
Mzwandile Erasmus ◽  
Jonathan Day ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Growth Inhibition ◽  
Whole Blood ◽  
Inhibition Assay ◽  
Growth Inhibition Assay ◽  
Mycobacterial Growth

scholarly journals Activity of nitazoxanide and tizoxanide against Mycobacterium tuberculosis in vitro and in whole blood culture

Tuberculosis ◽  
2016 ◽  
Vol 98 ◽  
pp. 92-96 ◽  
Author(s):  
Elizabeth P. Harausz ◽  
Keith A. Chervenak ◽  
Caryn E. Good ◽  
Michael R. Jacobs ◽  
Robert S. Wallis ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Blood Culture ◽  
Whole Blood

Mycobacterium tuberculosis-stimulated whole blood culture to detect host biosignatures for tuberculosis treatment response

Tuberculosis ◽  
2021 ◽  
pp. 102082
Author(s):  
Karen Cilliers ◽  
Angela Menezes ◽  
Tariq Webber ◽  
Hazel M. Dockrell ◽  
Jacqueline M. Cliff ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Blood Culture ◽  
Treatment Response ◽  
Whole Blood ◽  
Tuberculosis Treatment

Evaluation of the BBL MGIT (Mycobacterial Growth Indicator Tube) AST SIRE System for Antimycobacterial Susceptibility Testing of Mycobacterium tuberculosis to 4 Primary Antituberculous Drugs

2000 ◽  
Vol 124 (1) ◽  
pp. 82-86
Author(s):  
John S. Bergmann ◽  
Geoffrey Fish ◽  
Gail L. Woods
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Susceptibility Testing ◽  
Clinical Isolates ◽  
Indicator Tube ◽  
The Mean ◽  
Inoculum Preparation ◽  
Mycobacterial Growth ◽  
Mean Time ◽  
Mycobacterial Growth Indicator Tube ◽  
Growth Indicator

Abstract Objective.—To evaluate the performance of the BBL MGIT (Mycobacterial Growth Indicator Tube) AST SIRE system for the antimycobacterial susceptibility testing of Mycobacterium tuberculosis to isoniazid (at a concentration equivalent to the lower concentration used for testing by the method of proportion), rifampin, ethambutol, and streptomycin. Design.—Thirty-one clinical isolates and 30 challenge strains provided by the Centers for Disease Control and Prevention (CDC) were tested by MGIT AST SIRE using 2 methods of inoculum preparation, and results were compared with those of the method of proportion, which was considered the reference method. Clinical isolates for which the results of the 2 methods were discordant also were tested at 2 reference laboratories. Results.—Based on data from our site and the reference laboratories, agreement rates between initial MGIT AST SIRE results and the method of proportion for the clinical isolates with the inoculum prepared from a McFarland equivalent and from a positive MGIT tube, respectively, were 100% and 96.8% for isoniazid, 100% and 100% for rifampin, 96.8% and 100% for ethambutol, and 100% and 100% for streptomycin, excluding the isolate for which the discordant streptomycin result could not be resolved. For the 30 challenge isolates, agreement rates between MGIT AST SIRE and expected results and between method of proportion and expected results, respectively, were 96.7% and 93.3% for isoniazid, 93.3% and 100% for rifampin, 83.3% and 100% for ethambutol, and 93.3% and 100% for streptomycin. For the clinical isolates, the mean time to an MGIT AST SIRE result of susceptible was 6.15 ± 0.13 days (range, 5–8 days). For a result of resistant, the mean time overall was 5.00 ± 0.24 days (range, 3–8 days). Conclusion.—These data suggest that the MGIT AST SIRE system, using either method of inoculum preparation, is an acceptable alternative to the BACTEC 460 TB method of susceptibility testing of clinical isolates of M tuberculosis to isoniazid, rifampin, ethambutol, and streptomycin. Reasons for the lower agreement with the CDC challenge isolates should be investigated. Further evaluation of the MGIT AST SIRE system using a concentration of isoniazid equivalent to the higher concentration tested by the method of proportion would be useful, because the decision concerning use of this agent generally is based on the susceptibility test result at the higher concentration.

scholarly journals IRG1 controls immunometabolic host response and restricts intracellular Mycobacterium tuberculosis infection

2019 ◽  
Author(s):  
Eik Hoffmann ◽  
Arnaud Machelart ◽  
Imène Belhaouane ◽  
Nathalie Deboosere ◽  
Anne-Marie Pauwels ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Host Response ◽  
Immune Cell ◽  
Isocitrate Lyase ◽  
Metabolic Reprogramming ◽  
Host Cells ◽  
Wild Type ◽  
Term Survival ◽  
Major Player ◽  
Deficient Mice

AbstractMycobacterium tuberculosis (Mtb), the pathogen causing human tuberculosis, has evolved multiple strategies to successfully prevent clearance by immune cells and to establish dissemination and long-term survival in the host. The modulation of host immunity to maximize pathogen elimination while minimizing inflammation-mediated tissue damage may provide another tool to fight drug-resistant Mtb strains. Metabolic reprogramming of immune cell populations can dramatically influence the outcome of immune responses and modulate antimicrobial properties of infected host cells, nicely demonstrating that metabolites are tightly linked to immune cell effector functions. One important endogenous metabolite of the Krebs cycle is itaconate, which has potent bactericidal activity by inhibiting isocitrate lyase and the glyoxylate shunt within prokaryotes including mycobacteria. Recent findings show that itaconate and the catalytic enzyme responsible for its generation in mammalian cells, i.e. IRG1 (immune-responsive gene 1), also modify inflammatory signaling of infected cells enhancing host defense pathways.Here, we demonstrate that IRG1 is recruited to Mtb-containing phagosomes and that it influences the host response controlling Mtb infection. While IRG1 deficiency does not affect uptake of Mtb by macrophages and dendritic cells (DCs) in vitro, it increases the intracellular replication of Mtb. Concomitantly, in comparison to wild type cells, IRG1-deficient macrophages and DCs have increased levels of lipid droplets, a correlate of inflammation. These intracellular organelles store triacylglycerol and phospholipids that are hijacked by Mtb as reservoir of host nutrients. Exposure of IRG1-deficient mice to M. bovis BCG via the intranasal route induced neither lethality nor severe lung immunopathology, while IRG1-deficient mice were highly susceptible to Mtb infection resulting in animal death three weeks post-infection linked to exacerbated inflammation and high mycobacterial burden. The lungs of infected IRG1-deficient mice displayed large areas of necrotizing granulomatous inflammation and neutrophil infiltration, accompanied by reduced levels of B and T lymphocytes and increased levels of alveolar and interstitial macrophage populations, compared to their wild type counterparts. Therefore, our findings demonstrate that IRG1 is a major player in controlling the acute phase of Mtb infection with a specific effect on pathogenic mycobacteria.

scholarly journals Lack of Activity of Orally Administered Clofazimine against Intracellular Mycobacterium tuberculosis in Whole-Blood Culture

2004 ◽  
Vol 48 (8) ◽  
pp. 3133-3135 ◽  
Author(s):  
Ernestas Janulionis ◽  
Carolina Sofer ◽  
Ho-Yeon Song ◽  
Robert S. Wallis
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Blood Culture ◽  
Healthy Volunteers ◽  
Total Dose ◽  
Whole Blood ◽  
Active Drug ◽  
Multidrug Resistant ◽  
Blood Cultures ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis

ABSTRACT The activity of oral clofazimine against intracellular Mycobacterium tuberculosis was compared to that of ofloxacin in healthy volunteers by the use of whole-blood cultures. Clofazimine was inactive whether it was tested alone or combined with other drugs that are used to treat multidrug-resistant tuberculosis, despite a total dose of 2 g. Kanamycin was the most active drug tested.

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