The Capsule of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Modulates Phagosomal pH through Its Acid-Base Properties
ABSTRACT Phagosomal acidification is a critical cellular mechanism for the inhibition and killing of ingested microbes by phagocytic cells. The acidic environment activates microbicidal proteins and creates an unfavorable environment for the growth of many microbes. Consequently, numerous pathogenic...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2018-10-01
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| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mSphere.00437-18 |
| _version_ | 1818754508608503808 |
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| author | Carlos M. De Leon-Rodriguez Man Shun Fu M. Osman Çorbali Radames J. B. Cordero Arturo Casadevall |
| author_facet | Carlos M. De Leon-Rodriguez Man Shun Fu M. Osman Çorbali Radames J. B. Cordero Arturo Casadevall |
| author_sort | Carlos M. De Leon-Rodriguez |
| collection | DOAJ |
| description | ABSTRACT Phagosomal acidification is a critical cellular mechanism for the inhibition and killing of ingested microbes by phagocytic cells. The acidic environment activates microbicidal proteins and creates an unfavorable environment for the growth of many microbes. Consequently, numerous pathogenic microbes have developed strategies for countering phagosomal acidification through various mechanisms that include interference with phagosome maturation. The human-pathogenic fungus Cryptococcus neoformans resides in acidic phagosomes after macrophage ingestion that actually provides a favorable environment for replication, since the fungus replicates faster at acidic pH. We hypothesized that the glucuronic acid residues in the capsular polysaccharide had the capacity to affect phagosomal acidity through their acid-base properties. A ratiometric fluorescence comparison of imaged phagosomes containing C. neoformans to phagosomes containing beads showed that the latter were significantly more acidic. Similarly, phagosomes containing nonencapsulated C. neoformans cells were more acidic than those containing encapsulated cells. Acid-base titrations of isolated C. neoformans polysaccharide revealed that it behaves as a weak acid with maximal buffering capacity around pH 4 to 5. We interpret these results as indicating that the glucuronic acid residues in the C. neoformans capsular polysaccharide can buffer phagosomal acidification. Interference with phagosomal acidification represents a new function for the cryptococcal capsule in virulence and suggests the importance of considering the acid-base properties of microbial capsules in the host-microbe interaction for other microbes with charged residues in their capsules. IMPORTANCE Cryptococcus neoformans is the causative agent of cryptococcosis, a devastating fungal disease that affects thousands of individuals worldwide. This fungus has the capacity to survive inside phagocytic cells, which contributes to persistence of infection and dissemination. One of the major antimicrobial mechanisms of host phagocytes is to acidify the phagosomal compartment after ingestion of microbes. This study shows that the capsule of C. neoformans can interfere with full phagosomal acidification by serving as a buffer. |
| first_indexed | 2024-12-18T05:24:22Z |
| format | Article |
| id | doaj.art-05f37ae4ef304207b9554551aa9a0bf9 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-12-18T05:24:22Z |
| publishDate | 2018-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-05f37ae4ef304207b9554551aa9a0bf92022-12-21T21:19:34ZengAmerican Society for MicrobiologymSphere2379-50422018-10-013510.1128/mSphere.00437-18The Capsule of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Modulates Phagosomal pH through Its Acid-Base PropertiesCarlos M. De Leon-Rodriguez0Man Shun Fu1M. Osman Çorbali2Radames J. B. Cordero3Arturo Casadevall4Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USADepartment of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USADepartment of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USADepartment of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USADepartment of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USAABSTRACT Phagosomal acidification is a critical cellular mechanism for the inhibition and killing of ingested microbes by phagocytic cells. The acidic environment activates microbicidal proteins and creates an unfavorable environment for the growth of many microbes. Consequently, numerous pathogenic microbes have developed strategies for countering phagosomal acidification through various mechanisms that include interference with phagosome maturation. The human-pathogenic fungus Cryptococcus neoformans resides in acidic phagosomes after macrophage ingestion that actually provides a favorable environment for replication, since the fungus replicates faster at acidic pH. We hypothesized that the glucuronic acid residues in the capsular polysaccharide had the capacity to affect phagosomal acidity through their acid-base properties. A ratiometric fluorescence comparison of imaged phagosomes containing C. neoformans to phagosomes containing beads showed that the latter were significantly more acidic. Similarly, phagosomes containing nonencapsulated C. neoformans cells were more acidic than those containing encapsulated cells. Acid-base titrations of isolated C. neoformans polysaccharide revealed that it behaves as a weak acid with maximal buffering capacity around pH 4 to 5. We interpret these results as indicating that the glucuronic acid residues in the C. neoformans capsular polysaccharide can buffer phagosomal acidification. Interference with phagosomal acidification represents a new function for the cryptococcal capsule in virulence and suggests the importance of considering the acid-base properties of microbial capsules in the host-microbe interaction for other microbes with charged residues in their capsules. IMPORTANCE Cryptococcus neoformans is the causative agent of cryptococcosis, a devastating fungal disease that affects thousands of individuals worldwide. This fungus has the capacity to survive inside phagocytic cells, which contributes to persistence of infection and dissemination. One of the major antimicrobial mechanisms of host phagocytes is to acidify the phagosomal compartment after ingestion of microbes. This study shows that the capsule of C. neoformans can interfere with full phagosomal acidification by serving as a buffer.https://journals.asm.org/doi/10.1128/mSphere.00437-18CryptococcuscapsulepHphagosome |
| spellingShingle | Carlos M. De Leon-Rodriguez Man Shun Fu M. Osman Çorbali Radames J. B. Cordero Arturo Casadevall The Capsule of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Modulates Phagosomal pH through Its Acid-Base Properties mSphere Cryptococcus capsule pH phagosome |
| title | The Capsule of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Modulates Phagosomal pH through Its Acid-Base Properties |
| title_full | The Capsule of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Modulates Phagosomal pH through Its Acid-Base Properties |
| title_fullStr | The Capsule of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Modulates Phagosomal pH through Its Acid-Base Properties |
| title_full_unstemmed | The Capsule of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Modulates Phagosomal pH through Its Acid-Base Properties |
| title_short | The Capsule of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Modulates Phagosomal pH through Its Acid-Base Properties |
| title_sort | capsule of named content content type genus species cryptococcus neoformans named content modulates phagosomal ph through its acid base properties |
| topic | Cryptococcus capsule pH phagosome |
| url | https://journals.asm.org/doi/10.1128/mSphere.00437-18 |
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