Idiosyncratic Biogenesis of Intracellular Pathogens-Containing Vacuoles

Vaughn, Bethany; Kwaik, Yousef Abu

doi:10.3389/fcimb.2021.722433

Cited by 15 publications

(11 citation statements)

References 277 publications

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“…A property of a fully functional phagolysosome is its low pH (4.0 -4.5), conditions that not only are inhospitable to many organisms, but also result in activation of many proteases and other antimicrobial responses. Intracellular pathogens have evolved fascinating strategies to evade this process and survive in cells designed to eradicate them, and one of the most common strategies involve inhibition of phagosomal maturation (Vaughn and Abu Kwaik, 2021). Some pathogens, such as Listeria or Mycobacteria, escape from the phagosome before it acidifies; others, such as Salmonella or Legionella, remain in a modified phagosome that does not fuse with lysosomes.…”

Section: Introductionmentioning

confidence: 99%

Real-time visualization of phagosomal pH manipulation by Cryptococcus neoformans in an immune signal-dependent way

Santiago-Burgos

Stuckey

Santiago-Tirado

2022

Front. Cell. Infect. Microbiol.

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Understanding of how intracellular pathogens survive in their host cells is important to improve management of their diseases. This has been fruitful for intracellular bacteria, but it is an understudied area in fungal pathogens. Here we start elucidating and characterizing the strategies used by one of the commonest fungal pathogens, Cryptococcus neoformans, to survive intracellularly. The ability of the fungus to survive inside host cells is one of the main drivers of disease progression, yet it is unclear whether C. neoformans resides in a fully acidified, partially acidic, or neutral phagosome. Using a dye that only fluoresce under acidic conditions to stain C. neoformans, a hypha-defective Candida albicans mutant, and the nonpathogenic Saccharomyces cerevisiae, we characterized the fungal behaviors in infected macrophages by live microscopy. The main behavior in the C. albicans mutant strain and S. cerevisiae-phagosomes was rapid acidification after internalization, which remained for the duration of the imaging. In contrast, a significant number of C. neoformans-phagosomes exhibited alternative behaviors distinct from the normal phagosomal maturation: some phagosomes acidified with subsequent loss of acidification, and other phagosomes never acidified. Moreover, the frequency of these behaviors was affected by the immune status of the host cell. We applied the same technique to a flow cytometry analysis and found that a substantial percentage of C. neoformans-phagosomes showed impaired acidification, whereas almost 100% of the S. cerevisiae-phagosomes acidify. Lastly, using a membrane-damage reporter, we show phagosome permeabilization correlates with acidification alterations, but it is not the only strategy that C. neoformans uses to manipulate phagosomal acidification. The different behaviors described here provide an explanation to the confounding literature regarding cryptococcal-phagosome acidification and the methods can be applied to study other intracellular fungal pathogens.

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Section: Introductionmentioning

confidence: 99%

Real-time visualization of phagosomal pH manipulation by Cryptococcus neoformans in an immune signal-dependent way

Santiago-Burgos

Stuckey

Santiago-Tirado

2022

Front. Cell. Infect. Microbiol.

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“…The rhizobia that have entered the symplast of the host cell are kept separate from the host cytoplasm by the membrane, the source of which initially is the plasma membrane of the host cell [17,18]. The symbiosome has some structural analogy with pathogenic vacuoles that house microbes in mammals [29]. The bacterial pathogens Salmonella, Mycobacteria, Legionella, Chlamydia, and Brucella temporarily reside in membrane compartments-bacteria-containing vacuoles.…”

Section: Membranesources For Host Cell and Microsymbiont Expansionmentioning

confidence: 99%

“…The bacterial pathogens Salmonella, Mycobacteria, Legionella, Chlamydia, and Brucella temporarily reside in membrane compartments-bacteria-containing vacuoles. The modification of endocytic, exocytic, and/or ER-to-Golgi vesicle trafficking of invaded cells helps to maintain the bacterial population [29,30]. The pathogenic vacuoles mostly are destined to fuse with lysosomes of the host cell with a consequent lytic clearance of bacteria.…”

Section: Membranesources For Host Cell and Microsymbiont Expansionmentioning

confidence: 99%

“…Studies in plants have shown that most SNAREs are associated with specific intracellular compartments [39,40]. Some animal intracellular pathogens utilize the strategy of host cell mimicry; for example, Salmonella-containing vacuoles acquire Rab proteins and hence accept an identity similar to early/late endosomes [28,29].…”

Section: Symbiosome Identity and Symbiosome Membranementioning

confidence: 99%

See 1 more Smart Citation

Rapid Changes to Endomembrane System of Infected Root Nodule Cells to Adapt to Unusual Lifestyle

Fedorova

2023

IJMS

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Symbiosis between leguminous plants and soil bacteria rhizobia is a refined type of plant–microbial interaction that has a great importance to the global balance of nitrogen. The reduction of atmospheric nitrogen takes place in infected cells of a root nodule that serves as a temporary shelter for thousands of living bacteria, which, per se, is an unusual state of a eukaryotic cell. One of the most striking features of an infected cell is the drastic changes in the endomembrane system that occur after the entrance of bacteria to the host cell symplast. Mechanisms for maintaining intracellular bacterial colony represent an important part of symbiosis that have still not been sufficiently clarified. This review focuses on the changes that occur in an endomembrane system of infected cells and on the putative mechanisms of infected cell adaptation to its unusual lifestyle.

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“…A property of a fully functional phagolysosome is its low pH (4.0 – 4.5), conditions that not only are inhospitable to many organisms, but also result in activation of many proteases and other antimicrobial responses. Intracellular pathogens have evolved fascinating strategies to evade this process and survive in cells designed to eradicate them, and one of the most common strategies involve inhibition of phagosomal maturation (5). Some pathogens, such as Listeria or Mycobacteria , escape from the phagosome before it acidifies; others, such as Salmonella or Legionella , remain in a modified phagosome that does not fuse with lysosomes.…”

Section: Introductionmentioning

confidence: 99%

Real-time visualization of phagosomal pH manipulation by Cryptococcus neoformans in an immune signal-dependent way

Santiago-Burgos

Stuckey

Santiago-Tirado

2022

Preprint

View full text Add to dashboard Cite

Understanding of how intracellular pathogens survive in their host cells is important to improve management of their diseases. This has been fruitful for intracellular bacteria but it is an understudied area in fungal pathogens. Here we start elucidating and characterizing the strategies used by one of the commonest fungal pathogens, Cryptococcus neoformans, to survive intracellularly. The ability of the fungus to survive inside host cells is one of the main drivers of disease progression, yet it is unclear whether C. neoformans resides in a fully acidified, partially acidic, or neutral phagosome. Using a dye that only fluoresce under acidic conditions to stain C. neoformans, a hypha-defective Candida albicans mutant, and the nonpathogenic Saccharomyces cerevisiae, we characterized the fungal behaviors in infected macrophages by live microscopy. The main behavior in the C. albicans mutant strain and S. cerevisiae-phagosomes was rapid acidification after internalization, which remained for the duration of the imaging. In contrast, a significant number of C. neoformans-phagosomes exhibited alternative behaviors distinct from the normal phagosomal maturation: some phagosomes acidified with subsequent loss of acidification, and other phagosomes never acidified. Moreover, the frequency of these behaviors was affected by the immune status of the host cell. We applied the same technique to a flow cytometry analysis and found that a substantial percentage of C. neoformans-phagosomes showed impaired acidification, whereas almost 100% of the S. cerevisiae-phagosomes acidify. Lastly, using a membrane-damage reporter, we show phagosome permeabilization correlates with acidification alterations, but it is not the only strategy that C. neoformans uses to manipulate phagosomal acidification. The different behaviors described here provide an explanation to the confounding literature regarding cryptococcal-phagosome acidification and the methods can be applied to study other intracellular fungal pathogens.

show abstract

Idiosyncratic Biogenesis of Intracellular Pathogens-Containing Vacuoles

Cited by 15 publications

References 277 publications

Real-time visualization of phagosomal pH manipulation by Cryptococcus neoformans in an immune signal-dependent way

Real-time visualization of phagosomal pH manipulation by Cryptococcus neoformans in an immune signal-dependent way

Rapid Changes to Endomembrane System of Infected Root Nodule Cells to Adapt to Unusual Lifestyle

Real-time visualization of phagosomal pH manipulation by Cryptococcus neoformans in an immune signal-dependent way

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