Affiliation:
1. Department of Infectious Diseases, Huashan Hospital, Shanghai Institute of Infectious Disease and Biosecurity and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University , Shanghai, China
2. State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences , Beijing, China
Abstract
ABSTRACT
The human fungal pathogen
Candida albicans
colonizes and infects various host sites with diverse environmental pH. Adaptation to these diverse pH conditions plays a crucial role in its success as a commensal and pathogen. The conserved Rim101 pH sensing pathway is responsible for neutral–alkaline pH responses in
C. albicans
. In this study, we identified a novel Rfg1-Bcr1 regulatory pathway that governs acidic pH responses and regulates filamentation in
C. albicans
. A null mutant library was screened, and we have identified Rfg1 and Bcr1 as key regulators of filamentation under acidic pH conditions. Rfg1 directly binds to the promoter region of Bcr1 to regulate its transcriptional expression, which in turn suppresses the filamentation of
C. albicans
.
PHR1
, an alkaline pH response gene, is significantly activated by the absence of Rfg1, indicating that Rfg1 regulates acidic pH response through the Rim101-Phr1 pathway. Moreover, the cAMP signaling pathway, transcription factors Efg1 and Flo8, and the hyphal-specific G1 cyclin Hgc1 play critical roles in the regulation. Our findings provide new insights into the mechanisms underlying the acidic pH response of
C. albicans,
which reflects its elaborate regulatory control of environmental adaptation.
IMPORTANCE
Candida albicans
is a human commensal and frequent pathogen that encounters a wide range of pH stresses. The ability of
C. albicans
to adapt to changes in extracellular pH is crucial for its success in colonization and pathogenesis. The Rim101 pH sensing pathway is well known to govern neutral–alkaline pH responses in this pathogen. Here, we report a novel Rfg1-Bcr1 regulatory pathway that governs acidic pH responses and regulates filamentous growth in
C. albicans
. In addition, the Rim101-Phr1 pathway, cAMP signaling pathway, transcription factors Efg1 and Flo8, and hyphal-specific G1 cyclin Hgc1 cooperate with this regulation. Our findings provide new insights into the regulatory mechanism of acidic pH response in
C. albicans
.
Funder
MOST | National Key Research and Development Program of China
MOST | National Natural Science Foundation of China
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Cell Biology,Microbiology (medical),Genetics,General Immunology and Microbiology,Ecology,Physiology