Frontiers in Anti-infective Agents

Volume: 2

Inducing Autophagy to Eliminate Intracellular Bacteria

Author(s): Andy Ruiz and Esmeralda Juárez

Pp: 100-124 (25)

Doi: 10.2174/9789811469589120020007

* (Excluding Mailing and Handling)

Abstract

Autophagy is a lysosome-based degradation pathway of cytosolic cargos activated to prolong survival during starvation and diverse stress conditions by recycling of cellular content. In selective macroautophagy, specific cargos that could be misfolded proteins, damaged organelles, or intracellular pathogens selectively undergo degradation within autolysosomal compartments. However, some pathogens exhibit highly evolved tactics for evading autophagic recognition and are capable of surviving and replicating within the cytoplasm. Because autophagy is inducible in cells infected with pathogens that block autophagy, this mechanism has been proposed to be useful for therapy. In this chapter, we focus on Mycobacterium tuberculosis, one of the top causes of death worldwide and an archetype of intracellular pathogens, and its interaction with the autophagy machinery. First, we describe the generalities of the autophagic process and give examples of the bacterial strategies to evade or exploit autophagy. Also, we discuss the induction of autophagy as a therapeutic approach to circumvent the escape of bacteria from autophagy by using three types of autophagy inducers, the natural compounds, the microbial compound, and drugs. Also, we argue the main concerns that should be taken into account when using autophagy inducers as therapeutic agents.


Keywords: Autophagy, LC3, Tuberculosis, Macrophage, Immunomodulator, Rapamycin, Loperamide, MDP, Tri-DAD, NDGA.

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