PPE Surface Proteins Are Required for Heme Utilization by Mycobacterium tuberculosis

Area of Science:

• Microbiology
• Molecular Biology
• Biochemistry

Background:

• Tuberculosis, caused by Mycobacterium tuberculosis, affects millions globally.
• Iron is essential for M. tuberculosis replication, with heme being a major iron source.
• Mechanisms of heme uptake by M. tuberculosis remain poorly understood.

Purpose of the Study:

• To identify proteins involved in heme utilization by M. tuberculosis.
• To elucidate the role of novel surface proteins in iron acquisition.

Main Methods:

• Screening a transposon mutant library for resistance to gallium(III)-porphyrin (Ga-PIX).
• Growth experiments with isogenic deletion mutants.
• Surface plasmon resonance spectroscopy to confirm heme binding.

Main Results:

• Inactivation of ppe36, ppe62, and rv0265c genes conferred resistance to Ga-PIX.
• PPE36 is essential for heme utilization; PPE62 and Rv0265c have partially redundant functions.
• PPE36, PPE62, and Rv0265c bind heme and are membrane-associated.

Conclusions:

• Identified novel heme-binding proteins (PPE36, PPE62, Rv0265c) essential for M. tuberculosis iron acquisition.
• M. tuberculosis employs unique heme uptake systems distinct from other bacteria.
• PPE36 and PPE62 are the first identified proline-proline-glutamate (PPE) proteins involved in nutrient acquisition.