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PacC\/Rim signaling elicits the primary pH response in both model and pathogenic fungi and has been studied in multiple fungal species. In the predominant human pathogenic fungi, namely,\n            <jats:named-content content-type=\"genus-species\">Candida albicans<\/jats:named-content>\n            ,\n            <jats:named-content content-type=\"genus-species\">Aspergillus fumigatus<\/jats:named-content>\n            , and\n            <jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>\n            , this pathway is required for many functions associated with pathogenesis and virulence. Aspects of this pathway are fungus specific and do not exist in mammalian cells. In this review, we highlight recent advances in our understanding of PacC\/Rim-mediated functions and discuss the growing interest in this cascade and its factors as potential drug targets for antifungal strategies. We focus on both conserved and distinctive features in model and pathogenic fungi, highlighting the specificities of PacC\/Rim signaling in\n            <jats:named-content content-type=\"genus-species\">C. albicans<\/jats:named-content>\n            ,\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            , and\n            <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n            . We consider the role of this pathway in fungal virulence, including modulation of the host immune response. Finally, as now recognized for other signaling cascades, we highlight the role of pH in adaptation to antifungal drug pressure. By acting on the PacC\/Rim pathway, it may therefore be possible (i) to ensure fungal specificity and to limit the side effects of drugs, (ii) to ensure broad-spectrum efficacy, (iii) to attenuate fungal virulence, (iv) to obtain additive or synergistic effects with existing antifungal drugs through tolerance inhibition, and (v) to slow the emergence of resistant mutants.\n          <\/jats:p>","DOI":"10.1128\/ec.00313-13","type":"journal-article","created":{"date-parts":[[2014,1,18]],"date-time":"2014-01-18T04:02:55Z","timestamp":1390017775000},"page":"342-352","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":92,"title":["pH Signaling in Human Fungal Pathogens: a New Target for Antifungal Strategies"],"prefix":"10.1128","volume":"13","author":[{"given":"Muriel","family":"Cornet","sequence":"first","affiliation":[{"name":"Laboratoire TIMC-IMAG-TheREx, UMR 5525 CNRS-UJF, Universit\u00e9 Joseph Fourier, Grenoble, France"},{"name":"Parasitologie-Mycologie, Institut de Biologie et de Pathologie, CHU de Grenoble, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Gaillardin","sequence":"additional","affiliation":[{"name":"INRA, UMR1319 Micalis, Jouy-en-Josas, France"},{"name":"AgroParisTech, Micalis, Jouy-en-Josas, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004404"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.3109\/1048410903241444"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1835"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1567-1364.2009.00578.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1578"},{"key":"e_1_3_2_7_2","first-page":"856","article-title":"Signaling cascades as drug targets in model and pathogenic fungi","volume":"9","author":"Bastidas RJ","year":"2008","unstructured":"BastidasRJReedyJLMorales-JohanssonHHeitmanJCardenasME. 2008. 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