Evaluación del factor de transcripción Crz1 como nueva diana antifúngica para Candida auris multidrogo resistente mediante tecnología CRISPR Cas9

En los últimos años, las enfermedades fúngicas (EFIs) se han convertido en un problema de salud pública, debido a que 1,2 millones de personas en el mundo padecen estas infecciones. La mortalidad asociada con la EFI es similar a la de la tuberculosis y 3 veces más que la malariaADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.3390/jof3040057","ISSN":"2309-608X","PMID":"29371573","abstract":"Fungal diseases kill more than 1.5 million and affect over a billion people. However, they are still a neglected topic by public health authorities even though most deaths from fungal diseases are avoidable. Serious fungal infections occur as a consequence of other health problems including asthma, AIDS, cancer, organ transplantation and corticosteroid therapies. Early accurate diagnosis allows prompt antifungal therapy; however this is often delayed or unavailable leading to death, serious chronic illness or blindness. Recent global estimates have found 3,000,000 cases of chronic pulmonary aspergillosis, ~223,100 cases of cryptococcal meningitis complicating HIV/AIDS, ~700,000 cases of invasive candidiasis, ~500,000 cases of Pneumocystis jirovecii pneumonia, ~250,000 cases of invasive aspergillosis, ~100,000 cases of disseminated histoplasmosis, over 10,000,000 cases of fungal asthma and ~1,000,000 cases of fungal keratitis occur annually. Since 2013, the Leading International Fungal Education (LIFE) portal has facilitated the estimation of the burden of serious fungal infections country by country for over 5.7 billion people (>80% of the world's population). These studies have shown differences in the global burden between countries, within regions of the same country and between at risk populations. Here we interrogate the accuracy of these fungal infection burden estimates in the 43 published papers within the LIFE initiative.","author":[{"dropping-particle":"","family":"Bongomin","given":"Felix","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gago","given":"Sara","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Oladele","given":"Rita","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Denning","given":"David","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Fungi","id":"ITEM-1","issue":"4","issued":{"date-parts":[["2017","10","18"]]},"page":"57","title":"Global and Multi-National Prevalence of Fungal Diseases—Estimate Precision","type":"article-journal","volume":"3"},"uris":["http://www.mendeley.com/documents/?uuid=b517c477-e86f-3c56-8947-4e990efb972a"]}],"mendeley":{"formattedCitation":"(1)","plainTextFormattedCitation":"(1)","previouslyFormattedCitation":"(1)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(1). Los géneros Candida y Aspergillus son responsables del 70 a 90% de las EFIs. Candida spp., conforma un grupo de levaduras oportunistas, el principal agente etiológico es Candida albicans; Sin embargo, la prevalencia de especies no albicans (por ejemplo, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. auris) es creciente ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1093/jac/dkx444","ISSN":"0305-7453","author":[{"dropping-particle":"","family":"Lamoth","given":"Frederic","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lockhart","given":"Shawn R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Berkow","given":"Elizabeth L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Calandra","given":"Thierry","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Antimicrobial Chemotherapy","id":"ITEM-1","issue":"suppl_1","issued":{"date-parts":[["2018","1","1"]]},"page":"i4-i13","publisher":"Oxford University Press","title":"Changes in the epidemiological landscape of invasive candidiasis","type":"article-journal","volume":"73"},"uris":["http://www.mendeley.com/documents/?uuid=b8ed50e4-9891-3d23-8fc8-631834353f25"]},{"id":"ITEM-2","itemData":{"DOI":"10.5772/intechopen.81813","author":[{"dropping-particle":"","family":"Alberto Cortés","given":"Jorge","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fernanda Corrales","given":"Ivohne","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Fungal Infection","id":"ITEM-2","issued":{"date-parts":[["2018","11","10"]]},"publisher":"IntechOpen","title":"Invasive Candidiasis: Epidemiology and Risk Factors","type":"chapter"},"uris":["http://www.mendeley.com/documents/?uuid=9a55a4a9-5e87-3e94-964f-b82e3f99e63a"]}],"mendeley":{"formattedCitation":"(2,3)","plainTextFormattedCitation":"(2,3)","previouslyFormattedCitation":"(2,3)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(2,3). la especie más prevalente es C. albicans con una tasa de mortalidad del ~30%ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1093/jac/dkp507","PMID":"20106864","abstract":"OBJECTIVES Invasive fungal infections (IFIs) contribute significantly to mortality and morbidity in patients receiving myelosuppressive chemotherapy for haematological malignancies. The present study investigates the overall survival (OS), infection-related mortality and changes in treatment of IFIs in our department from 1995 until 2006. METHODS Outcomes of all chemotherapy courses were retrospectively evaluated using a standard questionnaire. Modified EORTC/MSG criteria for IFIs were applied: a positive PCR result for Aspergillus spp. in bronchoalveolar lavage was also defined as probable IFI. RESULTS In total, 1693 chemotherapy courses in 592 patients were evaluated. Sixty-three percent of chemotherapy courses were given to treat acute myeloid leukaemia, with the rest for acute lymphoblastic leukaemia or aggressive lymphoma. IFIs were observed in 139/592 patients [23.5%, 95% confidence interval (CI) 20%-27%] and in 149/1693 courses (8.8%, 95% CI 8%-10%). IFI-related mortality was 56.9% in 1995-2001 and 28.6% in 2002-06, P < 0.001. Accordingly, median OS in patients with IFI increased: 54 days (95% CI 26-82 days) in 1995-2001 versus 229 days (95% CI 35-423 days) in 2002-06, P = 0.001. By multivariate analysis, factors predictive for better OS were controlled disease after chemotherapy [hazard ratio (HR) 0.228, P < 0.001], possible IFI (in contrast to proven/probable IFI, HR 0.537, P = 0.005), age