ArticleThe Journal of clinical investigation2020
Macrophages use a bet-hedging strategy for antimicrobial activity in phagolysosomal acidification.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- A conserved enzymatic toolkit targeting host cell metabolism is associated with Cryptococcus neoformans intracellular survival in protozoal and mammalian phagocytic cells.PLoS pathogens · 2025Article
- Bioenergetic reprogramming of macrophages reduces drug tolerance in Mycobacterium tuberculosis.Nature communications · 2025Article
- Unraveling Mycobacterium tuberculosis acid resistance and pH homeostasis mechanisms.FEBS letters · 2025Review
- Polymeric Nanomaterials for Atherosclerosis Diagnosis and Treatment.Polymer science & technology (Washington, D.C.) · 2025Review
- Review
- Host-Pathogen Interactions and Correlated Factors That Are Affected in Replicative-AgedJournal of fungi (Basel, Switzerland) · 2024Article
- TcrXY is an acid-sensing two-component transcriptional regulator of Mycobacterium tuberculosis required for persistent infection.Nature communications · 2024Article
- Free Energy Barriers for Passive Drug Transport through theInternational journal of molecular sciences · 2024Article
- Exploring Peracetic Acid and Acidic pH Tolerance of Antibiotic-Resistant Non-TyphoidalMicroorganisms · 2023Article
- Replicative Acinetobacter baumannii strains interfere with phagosomal maturation by modulating the vacuolar pH.PLoS pathogens · 2023Article
- Article
- ReplicativebioRxiv : the preprint server for biology · 2023Article
- Bet-hedging antimicrobial strategies in macrophage phagosome acidification drive the dynamics of Cryptococcus neoformans intracellular escape mechanisms.PLoS pathogens · 2022Article
- When the Phagosome Gets Leaky: Pore-Forming Toxin-Induced Non-Canonical Autophagy (PINCA).Frontiers in cellular and infection microbiology · 2022Article
- Persistence ofFrontiers in cellular and infection microbiology · 2022Article
- Article
- Real-time visualization of phagosomal pH manipulation byFrontiers in cellular and infection microbiology · 2022Article
- Bet-hedging in innate and adaptive immune systems.Evolution, medicine, and public health · 2022Article
- Real-Time Simultaneous Imaging of Acidification and Proteolysis in Single Phagosomes Using Bifunctional Janus-Particle Probes.Angewandte Chemie (International ed. in English) · 2021Article
- Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Microbial ingestion by a macrophage results in the formation of an acidic phagolysosome but the host cell has no information on the pH susceptibility of the ingested organism. This poses a problem for the macrophage and raises the fundamental question of how the phagocytic cell optimizes the acidification process to prevail. We analyzed the dynamical distribution of phagolysosomal pH in murine and human macrophages that had ingested live or dead Cryptococcus neoformans cells, or inert beads. Phagolysosomal acidification produced a range of pH values that approximated normal distributions, but these differed from normality depending on ingested particle type. Analysis of the increments of pH reduction revealed no forbidden ordinal patterns, implying that the phagosomal acidification process was a stochastic dynamical system. Using simulation modeling, we determined that by stochastically acidifying a phagolysosome to a pH within the observed distribution, macrophages sacrificed a small amount of overall fitness to gain the benefit of reduced variation in fitness. Hence, chance in the final phagosomal pH introduces unpredictability to the outcome of the macrophage-microbe, which implies a bet-hedging strategy that benefits the macrophage. While bet hedging is common in biological systems at the organism level, our results show its use at the organelle and cellular level.
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Registered trials
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