Epigenetic control of pheromone MAPK signaling determines sexual fecundity in Candida albicans.

Several pathogenic Candida species are capable of heritable and reversible switching between two epigenetic states, "white" and "opaque." In Candida albicans, white cells are essentially sterile, whereas opaque cells are mating-proficient. Here, we interrogate the mechanism by which the white-opaque switch regulates sexual fecundity and identify four genes in the pheromone MAPK pathway that are expressed at significantly higher levels in opaque cells than in white cells. These genes encode the ß subunit of the G-protein complex (STE4), the pheromone MAPK scaffold (CST5), and the two terminal MAP kinases (CEK1/CEK2). To define the contribution of each factor to mating, C. albicans white cells were reverse-engineered to express elevated, opaque-like levels of these factors, either singly or in combination. We show that white cells co-overexpressing STE4, CST5, and CEK2 undergo mating four orders of magnitude more efficiently than control white cells and at a frequency approaching that of opaque cells. Moreover, engineered white cells recapitulate the transcriptional and morphological responses of opaque cells to pheromone. These results therefore reveal multiple bottlenecks in pheromone MAPK signaling in white cells and that alleviation of these bottlenecks enables efficient mating by these "sterile" cell types. Taken together, our findings establish that differential expression of several MAPK factors underlies the epigenetic control of mating in C. albicans We also discuss how fitness advantages could have driven the evolution of a toggle switch to regulate sexual reproduction in pathogenic Candida species.

Acceptability and feasibility of home-based hypertension and physical activity screening by community health workers in an under-resourced community in South Africa.

Background: Low-middle-income countries (LMICs) face increasing burdens from non-communicable disease (NCDs) requiring primary care task shifting to community health workers (CHWs). This study explored community members' perceptions of NCD-focused, CHW-led home visits in a historically disadvantaged township of South Africa. Methods: Trained CHWs visited community member homes, performing blood pressure and physical activity (PA) screenings, followed by brief counselling and a satisfaction survey. Semi-structured interviews were conducted within 3 days of the visit to learn about their experiences. Results: CHWs visited 173 households, with 153 adult community members consenting to participate (88.4%). Participants reported that it was easy to understand CHW-delivered information (97%), their questions were answered well (100%), and they would request home service again (93%). Twenty-eight follow-up interviews revealed four main themes: 1) acceptance of CHW visits, 2) openness to counselling, 3) satisfaction with screening and a basic understanding of the results, and 4) receptiveness to the PA advice. Conclusion: Community members viewed CHW-led home visits as an acceptable and feasible method for providing NCD-focused healthcare services in an under-resourced community. Expanding primary care reach through CHWs offers more accessible and individualized care, reducing barriers for individuals in under-resourced communities to access support for NCD risk reduction.