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Updated: Jul 6, 2026
A High-throughput Compatible Assay to Evaluate Drug Efficacy against Macrophage Passaged Mycobacterium tuberculosis
Published on: March 24, 2017
The TB laboratory of the future: macrophage-based selection of XDR-TB therapeutics
Marta Martins1, Miguel Viveiros, Leonard Amaral
1Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira, 96, 1349-008 Lisboa, Portugal.
Abstract:
Therapy of multidrug-resistant (MDR)-TB is highly problematic; that of extensively drug-resistant (XDR)-TB even more so. Both infections result in high mortality, especially if the patient is coinfected with HIV or presents with AIDS. Selection of therapy for these infections is limited and, for most situations, it is performed 'blind'. However, there is a solution for the selection of effective therapy and this is presented herein. Ideal therapy of the patient infected with MDR-TB or XDR-TB can be determined a priori by the mycobacteriology laboratory. This would involve the isolation of the patient's macrophages, the phagocytosis of the mycobacterial isolate and the presentation of the antitubercular agent to the macrophage-bacterium complex. This system is reviewed in its entirety and its potential and feasibility are supported by hard experimental demonstrations.
Insights
Selecting effective therapy for multidrug-resistant (MDR)-TB and extensively drug-resistant (XDR)-TB is challenging. A mycobacteriology laboratory method can determine ideal treatments a priori for better patient outcomes.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) pose significant treatment challenges.
- High mortality rates are associated with MDR-TB and XDR-TB, particularly in HIV/AIDS coinfected patients.
- Current therapeutic selection for these resistant TB forms is often empirical and limited.
Purpose of the Study:
- To present a novel solution for selecting effective antitubercular therapy for MDR-TB and XDR-TB.
- To demonstrate a method for a priori determination of ideal treatment regimens.
- To review the potential and feasibility of a mycobacteriology-based therapeutic selection system.
Main Methods:
- Isolation of patient-derived macrophages.
- Phagocytosis of clinical mycobacterial isolates by macrophages.
- In vitro presentation of antitubercular agents to the macrophage-bacterium complex.
Main Results:
- Experimental data supports the potential and feasibility of the proposed system.
- The method allows for the determination of ideal therapy before treatment initiation.
- This approach offers a viable alternative to empirical treatment selection.
Conclusions:
- A mycobacteriology laboratory-based system can guide the selection of optimal therapy for MDR-TB and XDR-TB.
- This method facilitates personalized treatment strategies for drug-resistant tuberculosis.
- The proposed system holds promise for improving treatment outcomes in challenging TB cases.
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