1. The role of Candida albicans transcription factor RLM1 in response to carbon adaptation
- Author
-
Oliveira-Pacheco, João, Alves, R., Costa-Barbosa, Augusto, Rodrigues, Bruno Cerqueira, Silva, Patrícia Pereira, Paiva, Sandra, Silva, Sónia Carina, Henriques, Mariana, Pais, Célia, Sampaio, Paula, and Universidade do Minho
- Subjects
0301 basic medicine ,Microbiology (medical) ,media_common.quotation_subject ,030106 microbiology ,lcsh:QR1-502 ,Microbiology ,lcsh:Microbiology ,Cell wall ,03 medical and health sciences ,Immune system ,C. albicans ,Secretion ,Internalization ,Candida albicans ,Original Research ,media_common ,2. Zero hunger ,lactate ,Science & Technology ,Ciências Naturais::Ciências Biológicas ,biology ,Chemistry ,Biofilm ,carbon adaptation ,biology.organism_classification ,candidiasis ,cell wall remodeling ,Corpus albicans ,3. Good health ,Cell biology ,Interleukin 10 ,030104 developmental biology ,alternative carbon sources ,RLM1 - Abstract
Candida albicans is the main causative agent of candidiasis and one of the most frequent causes of nosocomial infections worldwide. In order to establish an infection, this pathogen supports effective stress responses to counter host defenses and adapts to changes in the availability of important nutrients, such as alternative carbon sources. These stress responses have clear implications on the composition and structure of Candida cell wall. Therefore, we studied the impact of lactate, a physiologically relevant carbon source, on the activity of C. albicans RLM1 transcriptional factor. RLM1 is involved in the cell wall integrity pathway and plays an important role in regulating the flow of carbohydrates into cell wall biosynthesis pathways. The role of C. albicans RLM1 in response to lactate adaptation was assessed in respect to several virulence factors, such as the ability to grow under cell wall damaging agents, filament, adhere or form biofilm, as well as to immune recognition. The data showed that growth of C. albicans cells in the presence of lactate induces the secretion of tartaric acid, which has the potential to modulate the TCA cycle on both the yeast and the host cells. In addition, we found that adaptation of C. albicans cells to lactate reduces their internalization by immune cells and consequent % of killing, which could be correlated with a lower exposure of the cell wall -glucans. In addition, absence of RLM1 has a minor impact on internalization, compared with the wild-type and complemented strains, but it reduces the higher efficiency of lactate grown cells at damaging phagocytic cells and induces a high amount of IL-10, rendering these cells more tolerable to the immune system. The data suggests that RLM1 mediates cell wall remodeling during carbon adaptation, impacting their interaction with immune cells., This study was supported by the Portuguese National Funding Agency for Science, Research and Technology FCT. RA received FCT Ph.D. fellowship (PD/BD/113813/2015) and AC-B received FCT Ph.D. fellowship SFRH/BD/133513/2017. The work on CBMA was supported by FEDER through POFC-COMPETE and by FCT through strategic funding UID/BIA/04050/2013. The work on CEB was supported by Pest-OE/EQB/LA0023/2013, from FCT, "BioHealth - Biotechnology and Bioengineering approaches to improve health quality," Ref. NORTE-07-0124-FEDER-000027, co-funded by the Programa Operacional Regional do Norte (ON.2 - O Novo Norte), QREN, FEDER, and the project "Consolidating Research Expertise and Resources on Cellular and Molecular Biotechnology at CEB/IBB," Ref. FCOMP-01-0124-FEDER-027462., info:eu-repo/semantics/publishedVersion
- Published
- 2018