Journal Article

PPE64 is a mycomembrane channel protein that functions in heme iron uptake and moonlights in biofilm formation in Mycobacterium tuberculosis

Mitra, Avishek, Whitworth, Lisa, Stubbendieck, Reed M., Singh, Padam, Morgenstein, Randy, Kaufman, Charles B., Wozniak, Karen L.

2026

Overview

The success of any invading bacteria to survive within the host is dictated by their ability to acquire nutrients and overcome the host immune response. Bacterial cell surface proteins play critical roles in these processes at the host-pathogen interface. Here, we show that the PPE64 mycomembrane channel protein is required for heme iron acquisition and biofilm formation, which are fundamental processes that are of great significance to Mycobacterium tuberculosis ( Mtb ) survival within the host. These discrete functions of PPE64 are dictated by the culturing environment and are important for Mtb growth within human macrophages. These observations support an emerging theme in the Mtb field that the PPE protein family functions in trafficking molecules across the outer mycomembrane and has far-reaching implications for understanding of Mtb physiology.

• Publisher: American Society for Microbiology
• Subject: Alveoli / Antibiotics / Antigens, Bacterial - genetics / Antigens, Bacterial - metabolism / Bacteria / Bacterial Infections / Bacterial Pathogenesis / Bacterial Proteins - genetics / Bacterial Proteins - metabolism / Bacteriology / Binding sites / biofilm / Biofilms / Biofilms - growth & development / Biological Transport / Cell surface / Cell Wall Structure / Chronic and Persistent Infections / Clinical Microbiology and Infectious Diseases / Cloning / E coli / Experiments / Glycerol / Heme / Heme - metabolism / Humans / Hypotheses / Immune response / Intracellular Survival / Intracellular Survival of Mycobacterium Tuberculosis / Iron / Iron - metabolism / iron acquisition / Macrophages / Macrophages - microbiology / Microbial Pathogenesis and Immunology / Microbial Physiology and Genetics / Model Organisms / Monocytes / Mycobacterial Cell Wall / Mycobacterial Infections (E.g., Tuberculosis, Leprosy) / Mycobacteriology / Mycobacterium Tuberculosis / Mycobacterium tuberculosis - genetics / Mycobacterium tuberculosis - growth & development / Mycobacterium tuberculosis - metabolism / Mycobacterium tuberculosis - physiology / mycomembrane channel protein / Nutrients / outer membrane / Pathogen Biology and Host Interaction / Pathogen-Specific Immunity / Pathogenesis / Protein transport / Proteins / Research Article / Respiratory Infections / Ribonucleic acid / RNA / Tuberculosis / Tuberculosis Immunity / Tuberculosis Pathogenesis / Virulence / Virulence Factors and Mechanisms