Roles of Three Cryptococcus neoformans and Cryptococcus gattii Efflux Pump-Coding Genes in Response to Drug Treatment [Mechanisms of Resistance]
Chang, M., Sionov, E., Khanal Lamichhane, A., Kwon-Chung, K. J., Chang, Y. C.
The American Society for Microbiology (ASM)
Published 2018
The American Society for Microbiology (ASM)
Published 2018
| Publication Date: |
2018-03-28
|
|---|---|
| Publisher: |
The American Society for Microbiology (ASM)
|
| Print ISSN: |
0066-4804
|
| Electronic ISSN: |
1098-6596
|
| Topics: |
Biology
Medicine
|
| Published by: |
| _version_ | 1836398866436456448 |
|---|---|
| autor | Chang, M., Sionov, E., Khanal Lamichhane, A., Kwon-Chung, K. J., Chang, Y. C. |
| beschreibung | Cryptococcus neoformans and Cryptococcus gattii species complexes are the etiologic agents of cryptococcosis. We have deciphered the roles of three ABC transporters, Afr1, Afr2, and Mdr1, in the representative strains of the two species, C. neoformans H99 and C. gattii R265. Deletion of AFR1 in H99 and R265 drastically reduced the levels of resistance to three xenobiotics and three triazoles, suggesting that Afr1 is the major drug efflux pump in both strains. Fluconazole susceptibility was not affected when AFR2 or MDR1 was deleted in both strains. However, when these genes were deleted in combination with AFR1 , a minor additive effect in susceptibility toward several drugs was observed. Deletion of all three genes in both strains caused further increases in susceptibility toward fluconazole and itraconazole, suggesting that Afr2 and Mdr1 augment Afr1 function in pumping these triazoles. Intracellular accumulation of Nile Red significantly increased in afr1 mutants of both strains, but rhodamine 6G accumulation increased only in the mdr1 mutant of H99. Thus, the three efflux pumps play different roles in the two strains when exposed to different azoles and xenobiotics. AFR1 and AFR2 expression was upregulated in H99 and R265 when treated with fluconazole. However, MDR1 expression was upregulated only in R265 under the same conditions. We screened a library of transcription factor mutants and identified several mutants that manifested either altered fluconazole sensitivity or an increase in the frequency of fluconazole heteroresistance. Gene expression analysis suggests that the three efflux pumps are regulated independently by different transcription factors in response to fluconazole exposure. |
| citation_standardnr | 6218851 |
| datenlieferant | ipn_articles |
| feed_id | 515 |
| feed_publisher | The American Society for Microbiology (ASM) |
| feed_publisher_url | http://www.asm.org/ |
| insertion_date | 2018-03-28 |
| journaleissn | 1098-6596 |
| journalissn | 0066-4804 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | The American Society for Microbiology (ASM) |
| quelle | Antimicrobial Agents and Chemotherapy |
| relation | http://aac.asm.org/cgi/content/short/62/4/e01751-17?rss=1 |
| search_space | articles |
| shingle_author_1 | Chang, M., Sionov, E., Khanal Lamichhane, A., Kwon-Chung, K. J., Chang, Y. C. |
| shingle_author_2 | Chang, M., Sionov, E., Khanal Lamichhane, A., Kwon-Chung, K. J., Chang, Y. C. |
| shingle_author_3 | Chang, M., Sionov, E., Khanal Lamichhane, A., Kwon-Chung, K. J., Chang, Y. C. |
| shingle_author_4 | Chang, M., Sionov, E., Khanal Lamichhane, A., Kwon-Chung, K. J., Chang, Y. C. |
| shingle_catch_all_1 | Roles of Three Cryptococcus neoformans and Cryptococcus gattii Efflux Pump-Coding Genes in Response to Drug Treatment [Mechanisms of Resistance] Cryptococcus neoformans and Cryptococcus gattii species complexes are the etiologic agents of cryptococcosis. We have deciphered the roles of three ABC transporters, Afr1, Afr2, and Mdr1, in the representative strains of the two species, C. neoformans H99 and C. gattii R265. Deletion of AFR1 in H99 and R265 drastically reduced the levels of resistance to three xenobiotics and three triazoles, suggesting that Afr1 is the major drug efflux pump in both strains. Fluconazole susceptibility was not affected when AFR2 or MDR1 was deleted in both strains. However, when these genes were deleted in combination with AFR1 , a minor additive effect in susceptibility toward several drugs was observed. Deletion of all three genes in both strains caused further increases in susceptibility toward fluconazole and itraconazole, suggesting that Afr2 and Mdr1 augment Afr1 function in pumping these triazoles. Intracellular accumulation of Nile Red significantly increased in afr1 mutants of both strains, but rhodamine 6G accumulation increased only in the mdr1 mutant of H99. Thus, the three efflux pumps play different roles in the two strains when exposed to different azoles and xenobiotics. AFR1 and AFR2 expression was upregulated in H99 and R265 when treated with fluconazole. However, MDR1 expression was upregulated only in R265 under the same conditions. We screened a library of transcription factor mutants and identified several mutants that manifested either altered fluconazole sensitivity or an increase in the frequency of fluconazole heteroresistance. Gene expression analysis suggests that the three efflux pumps are regulated independently by different transcription factors in response to fluconazole exposure. Chang, M., Sionov, E., Khanal Lamichhane, A., Kwon-Chung, K. J., Chang, Y. C. The American Society for Microbiology (ASM) 0066-4804 00664804 1098-6596 10986596 |
| shingle_catch_all_2 | Roles of Three Cryptococcus neoformans and Cryptococcus gattii Efflux Pump-Coding Genes in Response to Drug Treatment [Mechanisms of Resistance] Cryptococcus neoformans and Cryptococcus gattii species complexes are the etiologic agents of cryptococcosis. We have deciphered the roles of three ABC transporters, Afr1, Afr2, and Mdr1, in the representative strains of the two species, C. neoformans H99 and C. gattii R265. Deletion of AFR1 in H99 and R265 drastically reduced the levels of resistance to three xenobiotics and three triazoles, suggesting that Afr1 is the major drug efflux pump in both strains. Fluconazole susceptibility was not affected when AFR2 or MDR1 was deleted in both strains. However, when these genes were deleted in combination with AFR1 , a minor additive effect in susceptibility toward several drugs was observed. Deletion of all three genes in both strains caused further increases in susceptibility toward fluconazole and itraconazole, suggesting that Afr2 and Mdr1 augment Afr1 function in pumping these triazoles. Intracellular accumulation of Nile Red significantly increased in afr1 mutants of both strains, but rhodamine 6G accumulation increased only in the mdr1 mutant of H99. Thus, the three efflux pumps play different roles in the two strains when exposed to different azoles and xenobiotics. AFR1 and AFR2 expression was upregulated in H99 and R265 when treated with fluconazole. However, MDR1 expression was upregulated only in R265 under the same conditions. We screened a library of transcription factor mutants and identified several mutants that manifested either altered fluconazole sensitivity or an increase in the frequency of fluconazole heteroresistance. Gene expression analysis suggests that the three efflux pumps are regulated independently by different transcription factors in response to fluconazole exposure. Chang, M., Sionov, E., Khanal Lamichhane, A., Kwon-Chung, K. J., Chang, Y. C. The American Society for Microbiology (ASM) 0066-4804 00664804 1098-6596 10986596 |
| shingle_catch_all_3 | Roles of Three Cryptococcus neoformans and Cryptococcus gattii Efflux Pump-Coding Genes in Response to Drug Treatment [Mechanisms of Resistance] Cryptococcus neoformans and Cryptococcus gattii species complexes are the etiologic agents of cryptococcosis. We have deciphered the roles of three ABC transporters, Afr1, Afr2, and Mdr1, in the representative strains of the two species, C. neoformans H99 and C. gattii R265. Deletion of AFR1 in H99 and R265 drastically reduced the levels of resistance to three xenobiotics and three triazoles, suggesting that Afr1 is the major drug efflux pump in both strains. Fluconazole susceptibility was not affected when AFR2 or MDR1 was deleted in both strains. However, when these genes were deleted in combination with AFR1 , a minor additive effect in susceptibility toward several drugs was observed. Deletion of all three genes in both strains caused further increases in susceptibility toward fluconazole and itraconazole, suggesting that Afr2 and Mdr1 augment Afr1 function in pumping these triazoles. Intracellular accumulation of Nile Red significantly increased in afr1 mutants of both strains, but rhodamine 6G accumulation increased only in the mdr1 mutant of H99. Thus, the three efflux pumps play different roles in the two strains when exposed to different azoles and xenobiotics. AFR1 and AFR2 expression was upregulated in H99 and R265 when treated with fluconazole. However, MDR1 expression was upregulated only in R265 under the same conditions. We screened a library of transcription factor mutants and identified several mutants that manifested either altered fluconazole sensitivity or an increase in the frequency of fluconazole heteroresistance. Gene expression analysis suggests that the three efflux pumps are regulated independently by different transcription factors in response to fluconazole exposure. Chang, M., Sionov, E., Khanal Lamichhane, A., Kwon-Chung, K. J., Chang, Y. C. The American Society for Microbiology (ASM) 0066-4804 00664804 1098-6596 10986596 |
| shingle_catch_all_4 | Roles of Three Cryptococcus neoformans and Cryptococcus gattii Efflux Pump-Coding Genes in Response to Drug Treatment [Mechanisms of Resistance] Cryptococcus neoformans and Cryptococcus gattii species complexes are the etiologic agents of cryptococcosis. We have deciphered the roles of three ABC transporters, Afr1, Afr2, and Mdr1, in the representative strains of the two species, C. neoformans H99 and C. gattii R265. Deletion of AFR1 in H99 and R265 drastically reduced the levels of resistance to three xenobiotics and three triazoles, suggesting that Afr1 is the major drug efflux pump in both strains. Fluconazole susceptibility was not affected when AFR2 or MDR1 was deleted in both strains. However, when these genes were deleted in combination with AFR1 , a minor additive effect in susceptibility toward several drugs was observed. Deletion of all three genes in both strains caused further increases in susceptibility toward fluconazole and itraconazole, suggesting that Afr2 and Mdr1 augment Afr1 function in pumping these triazoles. Intracellular accumulation of Nile Red significantly increased in afr1 mutants of both strains, but rhodamine 6G accumulation increased only in the mdr1 mutant of H99. Thus, the three efflux pumps play different roles in the two strains when exposed to different azoles and xenobiotics. AFR1 and AFR2 expression was upregulated in H99 and R265 when treated with fluconazole. However, MDR1 expression was upregulated only in R265 under the same conditions. We screened a library of transcription factor mutants and identified several mutants that manifested either altered fluconazole sensitivity or an increase in the frequency of fluconazole heteroresistance. Gene expression analysis suggests that the three efflux pumps are regulated independently by different transcription factors in response to fluconazole exposure. Chang, M., Sionov, E., Khanal Lamichhane, A., Kwon-Chung, K. J., Chang, Y. C. The American Society for Microbiology (ASM) 0066-4804 00664804 1098-6596 10986596 |
| shingle_title_1 | Roles of Three Cryptococcus neoformans and Cryptococcus gattii Efflux Pump-Coding Genes in Response to Drug Treatment [Mechanisms of Resistance] |
| shingle_title_2 | Roles of Three Cryptococcus neoformans and Cryptococcus gattii Efflux Pump-Coding Genes in Response to Drug Treatment [Mechanisms of Resistance] |
| shingle_title_3 | Roles of Three Cryptococcus neoformans and Cryptococcus gattii Efflux Pump-Coding Genes in Response to Drug Treatment [Mechanisms of Resistance] |
| shingle_title_4 | Roles of Three Cryptococcus neoformans and Cryptococcus gattii Efflux Pump-Coding Genes in Response to Drug Treatment [Mechanisms of Resistance] |
| timestamp | 2025-06-30T23:33:52.711Z |
| titel | Roles of Three Cryptococcus neoformans and Cryptococcus gattii Efflux Pump-Coding Genes in Response to Drug Treatment [Mechanisms of Resistance] |
| titel_suche | Roles of Three Cryptococcus neoformans and Cryptococcus gattii Efflux Pump-Coding Genes in Response to Drug Treatment [Mechanisms of Resistance] |
| topic | W WW-YZ |
| uid | ipn_articles_6218851 |