Loss of RPS41 but not its paralog RPS42 results in altered growth, filamentation and transcriptome changes in Candida albicans.
Although ribosomal proteins (RPs) are components of the ribosome, and function centrally in protein synthesis, several lines of evidence suggest that S4 ribosomal proteins (Rps4ps) can function in other cellular roles. In Candida albicans, ribosomal protein S4 (Rps4p) is encoded by two distinct but highly similar genes, RPS41 (C2_10620W_A) and RPS42 (C1_01640W_A). Previous studies indicated that in Saccharomyces cerevisiae loss of one isoform generated distinct phenotypes. To probe this relationship in C. albicans, rps41Δ and rps42Δ homozygous null mutants were generated. The transcript levels of the RPS41 and RPS42 genes are asymmetric in C. albicans, RPS41 mRNA levels were similar in wild-type strains and rps42Δ null mutants, while RPS42 gene transcript levels were induced 20 fold relative to wild type in rps41Δ null mutants. We found that the rps41Δ homozygous null mutant showed a reduced growth rate, and had defects in filament formation in liquid media and on solid media, while these phenotypes were not observed in the rps42Δ mutant strain. Neither the rps41Δ nor rps42Δ mutant strains displayed differential sensitivity to azoles, although intriguingly ectopic expression of either RPS41 or RPS42 in a wild-type strain leads to decreased sensitivity to fluconazole (FLC). C. albicans cDNA microarray analysis experiments found that carbohydrate and nitrogen metabolic processes were repressed but transport-process-related genes were up-regulated in the rps41Δ mutant. Overall, our present study suggests that loss of the RPS41 gene but not its paralog the RPS42 gene can generate distinct phenotypes including effects on growth rate, morphological transitions, and susceptibility to osmotic stress due to the fact that mRNA levels of RPS41 is much higher than RPS42 in C. albicans.
Center for New Drug Research, Department of Pharmacology, School of Pharmacy, Second Military Medical University, No. 325 Guohe Road, Shanghai 200433, China; Key Laboratory of the Plateau of the Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command, No. 333 Binhe South Road, Lanzhou 730050, China.
Hui
H
Lu
Center for New Drug Research, Department of Pharmacology, School of Pharmacy, Second Military Medical University, No. 325 Guohe Road, Shanghai 200433, China; Pharmacy Department, General Hospital of Jiangsu Armed Police, No. 8 Jiangdu South Road, Yangzhou 225000, China.
Xiang-Wen
XW
Yao
Biology Department, Concordia University, No. 7141 Sherbrooke Street West, Montreal, Quebec H4B 1R6, Canada.
Malcolm
M
Whiteway
Center for New Drug Research, Department of Pharmacology, School of Pharmacy, Second Military Medical University, No. 325 Guohe Road, Shanghai 200433, China; Key Laboratory of the Plateau of the Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command, No. 333 Binhe South Road, Lanzhou 730050, China.
Juan
J
Xiong
Center for New Drug Research, Department of Pharmacology, School of Pharmacy, Second Military Medical University, No. 325 Guohe Road, Shanghai 200433, China.
Ze-bin
ZB
Liao
Center for New Drug Research, Department of Pharmacology, School of Pharmacy, Second Military Medical University, No. 325 Guohe Road, Shanghai 200433, China. Electronic address: 13761571578@163.com.
Yuan-Ying
YY
Jiang
Center for New Drug Research, Department of Pharmacology, School of Pharmacy, Second Military Medical University, No. 325 Guohe Road, Shanghai 200433, China. Electronic address: caoyingying608@163.com.
Ying-Ying
YY
Cao
D002176:Candida albicans / Q000235:genetics* / Q000502:physiology; D015725:Fluconazole / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism*; D005658:Fungi / Q000235:genetics / Q000502:physiology; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D009154:Mutation; D009997:Osmotic Pressure; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects
D005656:Fungal Proteins; D012333:RNA, Messenger; D015725:Fluconazole
Candida albicans; Growth rate; Morphological transition; Ribosomal protein S4; cDNA microarrays