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Pathogenic diversity amongst serotype C VGIII and VGIV Cryptococcus gattii isolates.

Rodrigues J, Fonseca FL, Schneider RO, Godinho RM, Firacative C, Maszewska K, Meyer W, Schrank A, Staats C, Kmetzsch L, Vainstein MH, Rodrigues ML - Sci Rep (2015)

Bottom Line: This great phenotypic diversity reflected in differential pathogenicity.VGIV isolates WM 779 and 106.97 were similar in their ability to cause lethality and produced higher pulmonary fungal burden in a murine model of cryptococcosis, while isolate ATCC 24066 (VGIII) was unable to reach the brain and caused reduced lethality in intranasally infected mice.These results demonstrate a high diversity in the pathogenic potential of isolates of C. gattii belonging to the molecular types VGIII and VGIV.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Microbiologia Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

ABSTRACT
Cryptococcus gattii is one of the causative agents of human cryptococcosis. Highly virulent strains of serotype B C. gattii have been studied in detail, but little information is available on the pathogenic properties of serotype C isolates. In this study, we analyzed pathogenic determinants in three serotype C C. gattii isolates (106.97, ATCC 24066 and WM 779). Isolate ATCC 24066 (molecular type VGIII) differed from isolates WM 779 and 106.97 (both VGIV) in capsule dimensions, expression of CAP genes, chitooligomer distribution, and induction of host chitinase activity. Isolate WM 779 was more efficient than the others in producing pigments and all three isolates had distinct patterns of reactivity with antibodies to glucuronoxylomannan. This great phenotypic diversity reflected in differential pathogenicity. VGIV isolates WM 779 and 106.97 were similar in their ability to cause lethality and produced higher pulmonary fungal burden in a murine model of cryptococcosis, while isolate ATCC 24066 (VGIII) was unable to reach the brain and caused reduced lethality in intranasally infected mice. These results demonstrate a high diversity in the pathogenic potential of isolates of C. gattii belonging to the molecular types VGIII and VGIV.

No MeSH data available.


Related in: MedlinePlus

Analysis of C. gattii chitooligomers and host-derived chitinase activity.A. In vitro and in vivo detection of chitooligomers using TRITC-WGA. The typical polarized pattern of chitooligomer detection was observed in vitro. In vivo analysis revealed annular patterns of oligomer detection in isolates 106.97 and WM 779 and negative staining for the ATCC 24066 isolate. Scale bar, 5 μm. B. Pulmonary chitinase activity after infection with C. gattii. From day 14 to 21 post infection, chitinase activity was significantly higher when mice was infected with isolates 106.97 or WM 779, in comparison to the ATCC 24066 isolate (P < 0.05).
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f6: Analysis of C. gattii chitooligomers and host-derived chitinase activity.A. In vitro and in vivo detection of chitooligomers using TRITC-WGA. The typical polarized pattern of chitooligomer detection was observed in vitro. In vivo analysis revealed annular patterns of oligomer detection in isolates 106.97 and WM 779 and negative staining for the ATCC 24066 isolate. Scale bar, 5 μm. B. Pulmonary chitinase activity after infection with C. gattii. From day 14 to 21 post infection, chitinase activity was significantly higher when mice was infected with isolates 106.97 or WM 779, in comparison to the ATCC 24066 isolate (P < 0.05).

Mentions: Chitooligomers are readily detectable components of the cell wall-capsule interface in both C. neoformans and C. gattii (molecular type VGII)25. These structures participate in the architecture37 and biological functions38 of capsular components. We therefore evaluated whether chitooligomer detection varied among the three isolates studied here. Microscopic analysis of C. gattii cells grown in vitro revealed that all three isolates had the staining profile that was previously observed in C. gattii serotype B and C. neoformans serotype A isolates25, consisting of polarized regions of the cell wall recognized by WGA (Fig. 6A). Considering that the profile of chitooligomer detection in vivo varies depending on the induction of pulmonary chitinases37, we also tested the distribution of GlcNAc oligomers in these three isolates after infection of mice. In this analysis, 106.97 and WM 779 cells obtained from the lungs of infected animals had an annular pattern of chitooligomer staining. However, similar experiments with the ATCC 24066 isolate gave negative results for chitooligomer staining. We also tested the levels of chitinase activity in the lungs of infected mice (Fig. 6B). C. gattii 106.97 and WM 779 (annular detection of chitooligomers) induced chitinase activity in a time-dependent fashion. In contrast, C. gattii ATCC 24066 isolate (no chitooligomer detection) induced chitinase activity at the lowest levels.


Pathogenic diversity amongst serotype C VGIII and VGIV Cryptococcus gattii isolates.

Rodrigues J, Fonseca FL, Schneider RO, Godinho RM, Firacative C, Maszewska K, Meyer W, Schrank A, Staats C, Kmetzsch L, Vainstein MH, Rodrigues ML - Sci Rep (2015)

Analysis of C. gattii chitooligomers and host-derived chitinase activity.A. In vitro and in vivo detection of chitooligomers using TRITC-WGA. The typical polarized pattern of chitooligomer detection was observed in vitro. In vivo analysis revealed annular patterns of oligomer detection in isolates 106.97 and WM 779 and negative staining for the ATCC 24066 isolate. Scale bar, 5 μm. B. Pulmonary chitinase activity after infection with C. gattii. From day 14 to 21 post infection, chitinase activity was significantly higher when mice was infected with isolates 106.97 or WM 779, in comparison to the ATCC 24066 isolate (P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4495446&req=5

f6: Analysis of C. gattii chitooligomers and host-derived chitinase activity.A. In vitro and in vivo detection of chitooligomers using TRITC-WGA. The typical polarized pattern of chitooligomer detection was observed in vitro. In vivo analysis revealed annular patterns of oligomer detection in isolates 106.97 and WM 779 and negative staining for the ATCC 24066 isolate. Scale bar, 5 μm. B. Pulmonary chitinase activity after infection with C. gattii. From day 14 to 21 post infection, chitinase activity was significantly higher when mice was infected with isolates 106.97 or WM 779, in comparison to the ATCC 24066 isolate (P < 0.05).
Mentions: Chitooligomers are readily detectable components of the cell wall-capsule interface in both C. neoformans and C. gattii (molecular type VGII)25. These structures participate in the architecture37 and biological functions38 of capsular components. We therefore evaluated whether chitooligomer detection varied among the three isolates studied here. Microscopic analysis of C. gattii cells grown in vitro revealed that all three isolates had the staining profile that was previously observed in C. gattii serotype B and C. neoformans serotype A isolates25, consisting of polarized regions of the cell wall recognized by WGA (Fig. 6A). Considering that the profile of chitooligomer detection in vivo varies depending on the induction of pulmonary chitinases37, we also tested the distribution of GlcNAc oligomers in these three isolates after infection of mice. In this analysis, 106.97 and WM 779 cells obtained from the lungs of infected animals had an annular pattern of chitooligomer staining. However, similar experiments with the ATCC 24066 isolate gave negative results for chitooligomer staining. We also tested the levels of chitinase activity in the lungs of infected mice (Fig. 6B). C. gattii 106.97 and WM 779 (annular detection of chitooligomers) induced chitinase activity in a time-dependent fashion. In contrast, C. gattii ATCC 24066 isolate (no chitooligomer detection) induced chitinase activity at the lowest levels.

Bottom Line: This great phenotypic diversity reflected in differential pathogenicity.VGIV isolates WM 779 and 106.97 were similar in their ability to cause lethality and produced higher pulmonary fungal burden in a murine model of cryptococcosis, while isolate ATCC 24066 (VGIII) was unable to reach the brain and caused reduced lethality in intranasally infected mice.These results demonstrate a high diversity in the pathogenic potential of isolates of C. gattii belonging to the molecular types VGIII and VGIV.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Microbiologia Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

ABSTRACT
Cryptococcus gattii is one of the causative agents of human cryptococcosis. Highly virulent strains of serotype B C. gattii have been studied in detail, but little information is available on the pathogenic properties of serotype C isolates. In this study, we analyzed pathogenic determinants in three serotype C C. gattii isolates (106.97, ATCC 24066 and WM 779). Isolate ATCC 24066 (molecular type VGIII) differed from isolates WM 779 and 106.97 (both VGIV) in capsule dimensions, expression of CAP genes, chitooligomer distribution, and induction of host chitinase activity. Isolate WM 779 was more efficient than the others in producing pigments and all three isolates had distinct patterns of reactivity with antibodies to glucuronoxylomannan. This great phenotypic diversity reflected in differential pathogenicity. VGIV isolates WM 779 and 106.97 were similar in their ability to cause lethality and produced higher pulmonary fungal burden in a murine model of cryptococcosis, while isolate ATCC 24066 (VGIII) was unable to reach the brain and caused reduced lethality in intranasally infected mice. These results demonstrate a high diversity in the pathogenic potential of isolates of C. gattii belonging to the molecular types VGIII and VGIV.

No MeSH data available.


Related in: MedlinePlus