An audit of the medical pre-clinical curriculum at an urban university: sexual and gender minority health content.

Most medical students receive inadequate preparation to care for sexual and gender minority (SGM) patients. A review of one urban medical school's pre-clinical curriculum was conducted to assess coverage of appropriate SGM health content. Curricula that fully or partially addressed American Association of Medical Colleges (AAMC) core competencies for SGM health were categorized in an Excel spreadsheet. For partially met competencies, content that addressed the competency along with what was needed to fully address the competency were documented. AAMC SGM competencies that were not addressed at all were also noted. As a secondary source for triangulation, curricular topics were compared to SGM health content prioritized by Vanderbilt, a leader in championing inclusion of SGM content in medical curricula. Of the 30 AAMC competencies, 10 competencies were addressed, 11 were partially addressed, and 9 were not addressed. Gaps were noted in the AAMC domains of professionalism, systems-based practice, interprofessional collaboration, and personal/professional development. Among Vanderbilt topics, the George Washington University (GW) curriculum lacked content in intersex health, sexually transmitted infections (STIs) in lesbians, vaginitis in lesbians, efficacy of anal microbicides, anal Pap smears, and anal cancer risk and treatment for men who have sex with men (MSM). Despite these weaknesses, GW clocked greater than the national average at 7.5 hours of SGM content. This study provides a roadmap for curricular enhancements needed at GW as well as a prototype for other institutions to audit and improve curricular coverage on SGM health.

Recording of DNA-binding events reveals the importance of a repurposed Candida albicans regulatory network for gut commensalism.

Candida albicans is a fungal component of the human gut microbiota and an opportunistic pathogen. C. albicans transcription factors (TFs), Wor1 and Efg1, are master regulators of an epigenetic switch required for fungal mating that also control colonization of the mammalian gut. We show that additional mating regulators, WOR2, WOR3, WOR4, AHR1, CZF1, and SSN6, also influence gut commensalism. Using Calling Card-seq to record Candida TF DNA-binding events in the host, we examine the role and relationships of these regulators during murine gut colonization. By comparing in-host transcriptomes of regulatory mutants with enhanced versus diminished commensal fitness, we also identify a set of candidate commensalism effectors. These include Cht2, a GPI-linked chitinase whose gene is bound by Wor1, Czf1, and Efg1 in vivo, that we show promotes commensalism. Thus, the network required for a C. albicans sexual switch is biochemically active in the host intestine and repurposed to direct commensalism.

Candida albicans Morphogenesis Programs Control the Balance between Gut Commensalism and Invasive Infection.

Candida albicans is a gut commensal and opportunistic pathogen. The transition between yeast and invasive hyphae is central to virulence but has unknown functions during commensal growth. In a mouse model of colonization, yeast and hyphae co-occur throughout the gastrointestinal tract. However, competitive infections of C. albicans homozygous gene disruption mutants revealed an unanticipated, inhibitory role for the yeast-to-hypha morphogenesis program on commensalism. We show that the transcription factor Ume6, a master regulator of filamentation, inhibits gut colonization, not by effects on cell shape, but by activating the expression of a hypha-specific pro-inflammatory secreted protease, Sap6, and a hyphal cell surface adhesin, Hyr1. Like a ume6 mutant, strains lacking SAP6 exhibit enhanced colonization fitness, whereas SAP6-overexpression strains are attenuated in the gut. These results reveal a tradeoff between fungal programs supporting commensalism and virulence in which selection against hypha-specific markers limits the disease-causing potential of this ubiquitous commensal-pathogen.