Development of Echinocandin Resistance in Candida haemulonii: An Emergent, Widespread, and Opportunistic Fungal Pathogen
Abstract
:1. Introduction
2. Materials and Methods
2.1. Fungal Strain and Culture Conditions
2.2. Generation of the Echinocandin-Evolved C. haemulonii Strain
2.3. Antifungal Susceptibility Assay
2.4. Sequence Analysis of the FKS1 Gene
2.5. Growth Curves
2.6. Biofilm Formation
2.7. Chitin Content
2.8. Ultrastructural Architecture
2.9. Cell Wall Integrity and Stress Response
2.10. Macrophage Interaction
2.11. In Vivo Assays Using the Galleria mellonella Model
2.11.1. Larval Survival Assay
2.11.2. Hemocyte Density
2.11.3. Larvae Treatment with Antifungals
2.11.4. Fungal Burden
2.12. Statistical Analysis
3. Results
3.1. Generation and Altered Susceptibility in the Evolved C. haemulonii Strain
3.2. FKS1 Gene Analysis
3.3. Cell Wall Integrity and Stress Response
3.4. Acquisition of Resistance to CAS Is Associated with a Fitness Cost
3.5. Fungi–Macrophage Interplay
3.6. Acquisition of CAS Resistance Resulted in In Vivo Attenuated Virulence and Antifungal Resistance
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Antifungals | MIC Values (mg/L) | |||||
---|---|---|---|---|---|---|
Parental Strain | Evolved Strains Obtained under Different CAS Concentrations a | |||||
Ch4 | Ch4 0.25 mg/L | Ch4 0.5 mg/L | Ch4′r 1.0 mg/L | Ch4′r 2.0 mg/L | Ch4′r 4.0 mg/L | |
CAS | 0.5 | 0.5 | 0.5 | >16 | >16 | >16 |
MICA | 0.25 | 0.25 | 0.5 | >16 | >16 | >16 |
AND | 0.125 | 0.125 | 0.25 | >16 | >16 | >16 |
Genes | Nucleotide Sequence (Position/Mutation) | Amino Acid Sequence (Position/Mutation) | Fungal Strains |
---|---|---|---|
FKS1 HS1 | |||
1924—TTCTTGACTTTGTCCTTGAGAGATCCT | 635—FLTLSLRD | B11899 a | |
1924—TTCTTGACTTTGTCCTTGAGAGATCCT | 635—FLTLSLRD | Ch4 | |
1924—TTCTTGACTTTGTCCTTGAGAGATCCT | 635—FLTLSLRD | Ch4′r | |
FKS1 HS2 | |||
4048—GACTGGATTAGACGTTATACCTTG | 1350—DWIRRYT | B11899 a | |
4048—GACTGGATTAGACGTTATACCTTG | 1350—DWIRRYT | Ch4 | |
4048—GACTGGATTAGACATTATACCTTG | 1350—DWIRHYT | Ch4′r |
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Silva, L.N.; Ramos, L.S.; Oliveira, S.S.C.; Magalhães, L.B.; Cypriano, J.; Abreu, F.; Macedo, A.J.; Branquinha, M.H.; Santos, A.L.S. Development of Echinocandin Resistance in Candida haemulonii: An Emergent, Widespread, and Opportunistic Fungal Pathogen. J. Fungi 2023, 9, 859. https://doi.org/10.3390/jof9080859
Silva LN, Ramos LS, Oliveira SSC, Magalhães LB, Cypriano J, Abreu F, Macedo AJ, Branquinha MH, Santos ALS. Development of Echinocandin Resistance in Candida haemulonii: An Emergent, Widespread, and Opportunistic Fungal Pathogen. Journal of Fungi. 2023; 9(8):859. https://doi.org/10.3390/jof9080859
Chicago/Turabian StyleSilva, Laura N., Lívia S. Ramos, Simone S. C. Oliveira, Lucas B. Magalhães, Jefferson Cypriano, Fernanda Abreu, Alexandre J. Macedo, Marta H. Branquinha, and André L. S. Santos. 2023. "Development of Echinocandin Resistance in Candida haemulonii: An Emergent, Widespread, and Opportunistic Fungal Pathogen" Journal of Fungi 9, no. 8: 859. https://doi.org/10.3390/jof9080859