Effect of progesterone on Candida albicans biofilm formation under acidic conditions: A transcriptomic analysis.

Vulvovaginal candidiasis (VVC) caused by Candida albicans is a common disease worldwide. A very important C. albicans virulence factor is its ability to form biofilms on epithelium and/or on intrauterine devices promoting VVC. It has been shown that VVC has a hormonal dependency and that progesterone affects virulence traits of C. albicans cells. To understand how the acidic environment (pH 4) and progesterone (either alone and in combination) modulate C. albicans response during formation of biofilm, a transcriptomic analysis was performed together with characterization of the biofilm properties. Compared to planktonic cells, acidic biofilm-cells exhibited major changes in their transcriptome, including modifications in the expression of 286 genes that were not previously associated with biofilm formation in C. albicans. The vast majority of the genes up-regulated in the acidic biofilm cells (including those uniquely identified in our study) are known targets of Sfl1, and consistently, Sfl1 deletion is herein shown to impair the formation of acidic biofilms (pH 4). Under the acidic conditions used, the presence of progesterone reduced C. albicans biofilm biomass and structural cohesion. Transcriptomic analysis of biofilms developed in the presence of progesterone led to the identification of 65 down-regulated genes including, among others, the regulator Tec1 and several of its target genes, suggesting that the function of this transcription factor is inhibited by the presence of the hormone. Additionally, progesterone reduced the susceptibility of biofilm cells to fluconazole, consistent with an up-regulation of efflux pumps. Overall, the results of this study show that progesterone modulates C. albicans biofilm formation and genomic expression under acidic conditions, which may have implications for C. albicans pathogenicity in the vaginal environment.

The CgHaa1-Regulon Mediates Response and Tolerance to Acetic Acid Stress in the Human Pathogen Candida glabrata.

To thrive in the acidic vaginal tract, Candida glabrata has to cope with high concentrations of acetic acid. The mechanisms underlying C. glabrata tolerance to acetic acid at low pH remain largely uncharacterized. In this work, the essential role of the CgHaa1 transcription factor (encoded by ORF CAGL0L09339g) in the response and tolerance of C. glabrata to acetic acid is demonstrated. Transcriptomic analysis showed that CgHaa1 regulates, directly or indirectly, the expression of about 75% of the genes activated under acetic acid stress. CgHaa1-activated targets are involved in multiple physiological functions including membrane transport, metabolism of carbohydrates and amino acids, regulation of the activity of the plasma membrane H+-ATPase, and adhesion. Under acetic acid stress, CgHaa1 increased the activity and the expression of the CgPma1 proton pump and contributed to increased colonization of vaginal epithelial cells by C. glabrata CgHAA1, and two identified CgHaa1-activated targets, CgTPO3 and CgHSP30, are herein demonstrated to be determinants of C. glabrata tolerance to acetic acid. The protective effect of CgTpo3 and of CgHaa1 was linked to a role of these proteins in reducing the accumulation of acetic acid inside C. glabrata cells. In response to acetic acid stress, marked differences were found in the regulons controlled by CgHaa1 and by its S. cerevisiae ScHaa1 ortholog, demonstrating a clear divergent evolution of the two regulatory networks. The results gathered in this study significantly advance the understanding of the molecular mechanisms underlying the success of C. glabrata as a vaginal colonizer.

Tuberculosis multiorgánica en el Hospital Goyeneche de Arequipa, 1990 a 1994

Se realizó una revisión de cinco años (1990-1994) de pacientes internados con diagnóstico de tuberculosis en el Hospital Goyeneche de Arequipa-Perú; de 843 pacientes de tuberculosis, 107 (12.69 por ciento) presentaron tuberculosis multiorgánica, cuyo diagnóstico fue hecho al encontrar el bacilo tuberculoso, el granuloma tuberculoso o por clínica y prueba terapéutica. En 490 (49.10 por ciento) localizaciones se halló el bacilo de Koch; en 442 (44.29 por ciento) se realizó el diagnóstico por clínica y por prueba terapéutica y en 66 (6.61 por ciento) el diagnóstico fue por anatomía patológica. La mortalidad en tuberculosis pulmonar fue de 8.20 por ciento, en la tuberculosis extrapulmonar fue de 16.98 por ciento y en la tuberculosis multiorgánica fue de 15.89 por ciento. La tuberculosis multiorgánica mostró 41 formas de asociaciones, la asociación más frecuente fue pulmonar-pleural, que coincide con los hallazgos de V.Farga en Chile (9) y R.Ballón en otro hospital estatal de Arequipa (2). Tres pacientes tuvieron hasta seis localizaciones. El grupo etáreo más afectado, fue el de 15 a 45 años de edad. Los orgános o sistemas más afectados fueron: Pulmonar 75.26 por ciento, Pleural 15.72 por ciento, Enteroperitoneal 14.72 por ciento, Urinario 2.10 por ciento, Genital 1.10 por ciento y Laringea 0.80 por ciento. En la tuberculosis multiorgánica y extra-pulmonar en una sola localización, el número de varones y mujeres afectados es semejante, a diferencia con la tuberculosis solo pulmonar, que predominó en varones. En tres pacientes de sexo masculino con tuberculosis multiorgánica (cuyas edades fueron: 18, 27 y 55 años), se encontró asociado SIDA. A cinco pacientes se encontró tuberculosis multiorgánica por necropsia