The role of autophagy in intracellular pathogen nutrient acquisition

Abstract

Following entry into host cells intracellular pathogens must simultaneously evade innate host defense mechanisms and acquire energy and anabolic substrates from the nutrient-limited intracellular environment. Most of the potential intracellular nutrient sources are stored within complex macromolecules that are not immediately accessible by intracellular pathogens. To obtain nutrients for proliferation, intracellular pathogens must compete with the host cell for newly-imported simple nutrients or degrade host nutrient storage structures into their constituent components (fatty acids, carbohydrates, and amino acids). It is becoming increasingly evident that intracellular pathogens have evolved a wide variety of strategies to accomplish this task. One recurrent microbial strategy is to exploit host degradative processes that break down host macromolecules into simple nutrients that the microbe can use. Herein we focus on how a subset of bacterial, viral, and eukaryotic pathogens leverage the host process of autophagy to acquire nutrients that support their growth within infected cells.

Proteomic analysis of a mosquito host cell response to persistent Wolbachia infection

“…The suppressed proteins included Atg3 (0.71) and Atg5 (0.72), which have roles in the maturation of autophagosomes in canonical autophagy. In contrast, non-canonical Atg-5 independent autophagy is critical in the life cycle of some intracellular microbes, such as Francisella tularensis replication, infection by Brucella abortus , and entry into vacuoles by Mycobacterium marinum [28]. Other autophagy-related proteins, including clathrin heavy chain (0.89) and five coated pit and vesicle formation proteins, two dynein (0.93, 0.87) and three myosin motor proteins (0.76, 0.69, 0.60) were suppressed, in contrast to the elevated kinesin light (1.36) and heavy chain (1.24) subunits that carry cargo in anterograde transport to microtubule positive ends.…”

“…Formation of non-canonical pathogen-specific autophagosomes, or xenophagy, is initiated through different pathways, and recruits proteins that do not participate in the canonical pathway. Intracellular microbes including Anaplasma, Coxiella, Franciscella, Legionella, Mycobacterium , and Salmonella evade xenophagy while stimulating canonical autophagic processes that increase intracellular nutrient pools from which they benefit [28]. Anaplasma phagocytophilum , which like Wolbachia is classified in the Anaplasmataceae, modulates mitochondrial function and apoptosis through the secreted T4SS effector, Ats1.…”

“…Here we provide a quantitative proteomic analysis of the mosquito host cell response to w Str that suggests Wolbachia conforms to an emerging paradigm based on pathogenic intracellular bacteria in vertebrates that evade innate immunity responses and enhance access to host nutritional reserves [28, 29]. …”

Impact of lysosome status on extracellular vesicle content and release

“…Moreover, autophagy plays a role in the cellular immune system by engulfing intracellular pathogens and delivering them for degradation in the lysosomes (Steele, Brunton et al 2015). MVBs and lysosomes transport cargo from the endocytic and autophagy pathways and thus are major subcellular locations of invading pathogens.…”

Mechanistic insights into selective autophagy pathways: lessons from yeast

“…Conversely, the turnover of superfluous organelles happens in response to environmental stimuli 19 . Selective autophagy also degrades intracellular protein aggregates, pathogens and damaged organelles 20,21 . Similar to non-selective autophagy, selective autophagy is also activated by various external stimuli, including stresses such as oxidative, osmotic, hypoxic or starvation conditions 8–10 .…”