Blood antimicrobial activity varies against different Mycobacterium spp

Area of Science:

• Microbiology
• Immunology
• Infectious Diseases

Background:

• Traditional in vitro models for studying mycobacterial infections often use macrophages, which can be difficult to reproduce their antimycobacterial activity.
• Alternative models are needed to better understand mycobacterial pathogenicity and host susceptibility.

Purpose of the Study:

• To evaluate whole blood and leukocyte-in-plasma models for studying infections with various Mycobacterium species.
• To assess the influence of anticoagulants (heparin vs. EDTA) on mycobacterial survival and host immune responses in these models.

Main Methods:

• Infection of whole blood and leukocytes in plasma from QuantiFERON-negative individuals with Mycobacterium tuberculosis, M. avium, M. kansasii, M. chelonae, M. gordonae, and M. bovis.
• Comparison of bacterial enumeration after seven days in heparinized versus EDTA-treated blood.
• Assessment of EDTA's effect on cellular functions like cytokine production and reactive oxygen species (ROS) generation.

Main Results:

• The anticoagulant used significantly impacted infection outcomes; EDTA demonstrated a killing effect on mycobacteria, whereas heparin did not.
• EDTA exhibited bacteriostatic rather than bactericidal effects, inhibiting bacterial growth without direct killing.
• Rapidly growing M. chelonae multiplied in heparinized models but was eliminated in EDTA models.

Conclusions:

• Whole blood models, particularly with EDTA, offer a promising alternative to traditional macrophage models for studying mycobacterial infections.
• EDTA's influence on bacterial survival warrants further investigation to understand its role in antimycobacterial activity.
• These blood-derived models may provide a more relevant system for assessing host susceptibility and evaluating potential therapeutics.