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Updated: Dec 15, 2025
Identification of Virulence Markers of Mycobacterium abscessus for Intracellular Replication in Phagocytes
Published on: September 27, 2018
Mycobacteria and the intraphagosomal environment: take it with a pinch of salt(s)!
Thierry Soldati1, Olivier Neyrolles
1Départment de Biochimie, Faculté des Sciences, Université de Genève, Sciences II, 30 quai Ernest Ansermet, CH-1211, Genève-4, Switzerland. Thierry.Soldati@unige.ch
Abstract:
Ancient protozoan phagocytes and modern professional phagocytes of metazoans, such as macrophages, employ evolutionarily conserved mechanisms to kill microbes. These mechanisms rely on microbial ingestion, followed by maturation of the phagocytic vacuole, or so-called phagosome. Phagosome maturation includes a series of fusion and fission events with the host cell endosomes and lysosomes, leading to a rapid increase of the degradative properties of the vacuole and to the destruction of the ingested microbe within a very hostile intracellular compartment, the phagolysosome. Historically, the mechanisms and weapons used by phagocytes to kill microbes have been separated into different classes. Phagosomal acidification, together with the production of reactive oxygen and nitrogen species, the selective manipulation of various ions in the phagosomal lumen, and finally the engagement of a battery of acidic hydrolases, are well-recognized players in this process. However, it is relatively recently that interconnections among these mechanisms have become apparent. In this review, we will focus on some emerging concepts about these interconnected aspects of the warfare at the host-pathogen interface, using mostly Mycobacterium tuberculosis as an example of intracellular pathogen. In particular, recent discoveries on the role of phagosomal ions and other chemicals in the control of pathogens, as well as mechanisms evolved by intracellular pathogens to circumvent or even exploit the weapons of the host cell will be discussed.
Insights
Phagocytes use conserved mechanisms to kill microbes, involving phagosome maturation and hostile environments. Emerging research reveals interconnections between these microbial killing strategies, particularly in Mycobacterium tuberculosis infections.
Area of Science:
- Cellular and Molecular Immunology
- Microbiology
- Host-Pathogen Interactions
Background:
- Professional phagocytes, like macrophages, utilize evolutionarily conserved mechanisms to eliminate ingested microbes.
- Phagosome maturation, involving fusion with endosomes and lysosomes, creates a degradative phagolysosome essential for microbial destruction.
- Traditional understanding separated phagocyte killing mechanisms, including acidification, reactive species production, ion manipulation, and hydrolases.
Purpose of the Study:
- To review emerging concepts on the interconnectedness of phagocyte-mediated microbial killing mechanisms.
- To highlight the role of phagosomal ions and chemicals in pathogen control.
- To discuss pathogen strategies for evading or exploiting host cell defenses, using Mycobacterium tuberculosis as a model.
Main Methods:
- Review of recent scientific literature focusing on host-pathogen interactions and phagosome biology.
- Analysis of established and novel mechanisms of microbial killing within phagocytes.
- Case study focusing on Mycobacterium tuberculosis and its interaction with host phagocytes.
Main Results:
- Interconnections among previously disparate phagocyte killing mechanisms are becoming apparent.
- Phagosomal ion concentrations and other chemical factors play a significant role in controlling intracellular pathogens.
- Intracellular pathogens have evolved sophisticated mechanisms to counteract or hijack host defenses.
Conclusions:
- Understanding the integrated warfare at the host-pathogen interface is crucial for developing effective anti-microbial strategies.
- Phagosomal ion dynamics and chemical signaling represent key areas for future research in host defense.
- Targeting pathogen evasion mechanisms could provide novel therapeutic avenues against intracellular infections.
