Metatranscriptomics reveals metabolic adaptation and induction of virulence factors by Haemophilus parasuis during lung infection

International audienceAbstractHaemophilus parasuis is a common inhabitant of the upper respiratory tract of pigs, and the causative agent of Glässer’s disease. This disease is characterized by polyserositis and arthritis, produced by the severe inflammation caused by the systemic spread of the bacterium. After an initial colonization of the upper respiratory tract, H. parasuis enters the lung during the early stages of pig infection. In order to study gene expression at this location, we sequenced the ex vivo and in vivo H. parasuis Nagasaki transcriptome in the lung using a metatranscriptomic approach. Comparison of gene expression under these conditions with that found in conventional plate culture showed generally reduced expression of genes associated with anabolic and catabolic pathways, coupled with up-regulation of membrane-related genes involved in carbon acquisition, iron binding and pathogenesis. Some of the up-regulated membrane genes, including ABC transporters, virulence-associated autotransporters (vtaAs) and several hypothetical proteins, were only present in virulent H. parasuis strains, highlighting their significance as markers of disease potential. Finally, the analysis also revealed the presence of numerous antisense transcripts with possible roles in gene regulation. In summary, this data sheds some light on the scarcely studied in vivo transcriptome of H. parasuis, revealing nutritional virulence as an adaptive strategy for host survival, besides induction of classical virulence factors

Education efforts may contribute to wider acceptance of human papillomavirus self-sampling

Victoria Crofts,1,* Emmanuel Flahault,1,* Pierre-Marie Tebeu,2 Sarah Untiet,3 Gisèle Kengne Fosso,2 Michel Boulvain,3 Pierre Vassilakos,4 Patrick Petignat3 1Faculty of Medicine, University of Geneva, Geneva, Switzerland; 2Department of Gynecology and Obstetrics, University Center Hospital, Yaoundé, Cameroon; 3Department of Gynecology and Obstetrics, Geneva University Hospitals, Geneva, Switzerland; 4Geneva Foundation for Medical Education and Research, Geneva, Switzerland *These authors contributed equally to this paper Background: Information about women’s acceptance of new screening methods in Sub-Saharan Africa is limited. The aim of this study was to report on women’s acceptance of human papillomavirus (HPV) self-sampling following an educational intervention on cervical cancer and HPV.Methods: Women were recruited from the city of Tiko and a low-income neighborhood of Yaoundé, both in Cameroon. Written and oral instructions about how to perform an unsupervised HPV self-sample were given to participants, who performed the test in a private room. Acceptability of HPV self-sampling was evaluated by questionnaire. Participants previously screened for cervical cancer by a physician were asked additional questions to assess their personal preferences about HPV self-sampling.Results: A sample of 540 women were prospectively enrolled in the study; median age was 43 years old (range 30–65 years). Participants expressed a high level of acceptance of HPV self-sampling as a screening method following information sessions about cervical cancer and HPV. Most expressed no embarrassment, pain, anxiety, or discomfort (95.6%, 87.8%, 91.3%, and 85.0%, respectively) during the information sessions. Acceptance of the method had no correlation with education, knowledge, age, or socio-professional class. Eighty-six women (16%) had a history of previous screening; they also reported high acceptance of HPV self-sampling.Conclusion: Educational interventions on cancer and HPV were associated with high acceptability of HPV self-testing by Cameroonian women. Further evaluation of the intervention in a larger sample and using a control group is recommended.Keywords: Cameroon women, cervical cancer screening, HPV, low-resource country, physician sampling, self-samplin

CLCN2 chloride channel mutations in familial hyperaldosteronism type II

Primary aldosteronism, a common cause of severe hypertension 1 , features constitutive production of the adrenal steroid aldosterone. We analyzed a multiplex family with familial hyperaldosteronism type II (FH-II) 2 and 80 additional probands with unsolved early-onset primary aldosteronism. Eight probands had novel heterozygous variants in CLCN2, including two de novo mutations and four independent occurrences of a mutation encoding an identical p.Arg172Gln substitution; all relatives with early-onset primary aldosteronism carried the CLCN2 variant found in the proband. CLCN2 encodes a voltage-gated chloride channel expressed in adrenal glomerulosa that opens at hyperpolarized membrane potentials. Channel opening depolarizes glomerulosa cells and induces expression of aldosterone synthase, the rate-limiting enzyme for aldosterone biosynthesis. Mutant channels show gain of function, with higher open probabilities at the glomerulosa resting potential. These findings for the first time demonstrate a role of anion channels in glomerulosa membrane potential determination, aldosterone production and hypertension. They establish the cause of a substantial fraction of early-onset primary aldosteronism

CLCN2 chloride channel mutations in familial hyperaldosteronism type II

Primary aldosteronism, a common cause of severe hypertension1, features constitutive production of the adrenal steroid aldosterone. We analyzed a multiplex family with familial hyperaldosteronism type II (FH-II)2 and 80 additional probands with unsolved early-onset primary aldosteronism. Eight probands had novel heterozygous variants in CLCN2, including two de novo mutations and four independent occurrences of a mutation encoding an identical p.Arg172Gln substitution; all relatives with early-onset primary aldosteronism carried the CLCN2 variant found in the proband. CLCN2 encodes a voltage-gated chloride channel expressed in adrenal glomerulosa that opens at hyperpolarized membrane potentials. Channel opening depolarizes glomerulosa cells and induces expression of aldosterone synthase, the rate-limiting enzyme for aldosterone biosynthesis. Mutant channels show gain of function, with higher open probabilities at the glomerulosa resting potential. These findings for the first time demonstrate a role of anion channels in glomerulosa membrane potential determination, aldosterone production and hypertension. They establish the cause of a substantial fraction of early-onset primary aldosteronism