biostudies-literatureRai MNResearch Services and Knowledge Transfer Office, University of MacauFundo para o Desenvolvimento das Ciências e da Tecnologiae73832https://www.ebi.ac.uk/biostudies/studies/S-EPMC11554308biostudies-literatureUnknown13<i>Candida glabrata</i> can thrive inside macrophages and tolerate high levels of azole antifungals. These innate abilities render infections by this human pathogen a clinical challenge. How <i>C. glabrata</i> reacts inside macrophages and what is the molecular basis of its drug tolerance are not well understood. Here, we mapped genome-wide RNA polymerase II (RNAPII) occupancy in <i>C. glabrata</i> to delineate its transcriptional responses during macrophage infection in high temporal resolution. RNAPII profiles revealed dynamic <i>C. glabrata</i> responses to macrophages with genes of specialized pathways activated chronologically at different times of infection. We identified an uncharacterized transcription factor (CgXbp1) important for the chronological macrophage response, survival ineLifeTemporal transcriptional response of <i>Candida glabrata</i> during macrophage infection reveals a multifaceted transcriptional regulator CgXbp1 important for macrophage response and fluconazole resistance.PMC115543080033/2021/A1MYRG2019-00099-FHSMYRG2022-00107-FHS0099/2022/A2Shen LTan KRai MNParsania CLan QWong KHRai RChen RShirgaonkar NfalseTemporal transcriptional response of <i>Candida glabrata</i> during macrophage infection reveals a multifaceted transcriptional regulator CgXbp1 important for macrophage response and fluconazole resistance.<i>Candida glabrata</i> can thrive inside macrophages and tolerate high levels of azole antifungals. These innate abilities render infections by this human pathogen a clinical challenge. How <i>C. glabrata</i> reacts inside macrophages and what is the molecular basis of its drug tolerance are not well understood. Here, we mapped genome-wide RNA polymerase II (RNAPII) occupancy in <i>C. glabrata</i> to delineate its transcriptional responses during macrophage infection in high temporal resolution. RNAPII profiles revealed dynamic <i>C. glabrata</i> responses to macrophages with genes of specialized pathways activated chronologically at different times of infection. We identified an uncharacterized transcription factor (CgXbp1) important for the chronological macrophage response, survival in2024-01-01T00:00:00Z2024 Oct2026-07-09T12:18:27.379Z2025-04-07T08:47:02.11ZS-EPMC115543083935673910.7554/eLife.73832