{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:59:06Z","timestamp":1790949546852,"version":"4.1.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2008,3,1]],"date-time":"2008-03-01T00:00:00Z","timestamp":1204329600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2008,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    There is concern about the rise of antifungal drug resistance, but little is known about comparative biological properties and pathogenicity of drug-resistant strains. We generated fluconazole (FLC; CO23\n                    <jats:sub>RFLC<\/jats:sub>\n                    )- or micafungin (FK; CO23\n                    <jats:sub>RFK<\/jats:sub>\n                    )-resistant strains of\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    by treating a FLC- and FK-susceptible strain of this fungus (CO23\n                    <jats:sub>S<\/jats:sub>\n                    ) with stepwise-increasing concentrations of either drug. Molecular analyses showed that CO23\n                    <jats:sub>RFLC<\/jats:sub>\n                    had acquired markedly increased expression of the drug-resistance efflux pump encoded by the\n                    <jats:italic>MDR1<\/jats:italic>\n                    gene, whereas CO23\n                    <jats:sub>RFK<\/jats:sub>\n                    had a homozygous mutation in the\n                    <jats:italic>FSK1<\/jats:italic>\n                    gene. These genetic modifications did not alter to any extent the growth capacity of the drug-resistant strains in vitro, either at 28\u00b0C or at 37\u00b0C, but markedly increased their experimental pathogenicity in a systemic mouse infection model, as assessed by the overall mortality and target organ invasion. Interestingly, no apparent increase in the vaginopathic potential of the strains was observed with an estrogen-dependent rat vaginal infection. The increased pathogenicity of drug-resistant strains for systemic infection was associated with a number of biochemical and physiological changes, including (i) marked cellular alterations associated with a different expression and content of major cell wall polysaccharides, (ii) more rapid and extensive hypha formation in both liquid and solid media, and (iii) increased adherence to plastic and a propensity for biofilm formation. Overall, our data demonstrate that experimentally induced resistance to antifungal drugs, irrespective of drug family, can substantially divert\n                    <jats:italic>C. albicans<\/jats:italic>\n                    biology, affecting in particular biological properties of potential relevance for deep-seated candidiasis.\n                  <\/jats:p>","DOI":"10.1128\/aac.01223-07","type":"journal-article","created":{"date-parts":[[2008,1,7]],"date-time":"2008-01-07T20:43:40Z","timestamp":1199738620000},"page":"927-936","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":57,"title":["Increase of Virulence and Its Phenotypic Traits in Drug-Resistant Strains of\n                    <i>Candida albicans<\/i>"],"prefix":"10.1128","volume":"52","author":[{"given":"Letizia","family":"Angiolella","sequence":"first","affiliation":[{"name":"Department of Public Health Sciences G. Sanarelli, University of Rome \u201cLa Sapienza,\u201d Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Rita","family":"Stringaro","sequence":"additional","affiliation":[{"name":"Department of Technology and Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"De Bernardis","sequence":"additional","affiliation":[{"name":"Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanita\u0300, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brunella","family":"Posteraro","sequence":"additional","affiliation":[{"name":"Istituto di Microbiologia, Universita\u0300 Cattolica del Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariantonietta","family":"Bonito","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences G. 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