Increase of virulence and its phenotypic traits in drug-resistant strains of Candida albicans

Letizia Angiolella, Anna Rita Stringaro, Flavia De Bernardis, Brunella Posteraro, Mariantonietta Bonito, Laura Toccacieli, Antonella Torosantucci, Marisa Colone, Maurizio Sanguinetti, Antonio Cassone, Anna Teresa Palamara

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Abstract

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; C023RFLC)- or micafungin (FK; CO23RFK)-resistant strains of Candida albicans by treating a FLC- and FK-susceptible strain of this fungus (CO23S) with stepwise-increasing concentrations of either drug. Molecular analyses showed that CO23RFLC had acquired markedly increased expression of the drug-resistance efflux pump encoded by the MDR1 gene, whereas CO23RFK had a homozygous mutation in the FSK1 gene. These genetic modifications did not alter to any extent the growth capacity of the drug-resistant strains in vitro, either at 28°C or at 37°C, 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 bionlm formation. Overall, our data demonstrate that experimentally induced resistance to antifungal drugs, irrespective of drug family, can substantially divert C. albicans biology, affecting in particular biological properties of potential relevance for deep-seated candidiasis.

Original languageEnglish
Pages (from-to)927-936
Number of pages10
JournalAntimicrobial Agents and Chemotherapy
Volume52
Issue number3
DOIs
Publication statusPublished - Mar 2008

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Candida albicans
Virulence
Fungal Drug Resistance
Pharmaceutical Preparations
Infection
Hyphae
Fluconazole
Candidiasis
Drug Resistance
Cell Wall
Genes
Plastics
Polysaccharides
Estrogens
Fungi
Mutation
Mortality
Growth

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Increase of virulence and its phenotypic traits in drug-resistant strains of Candida albicans. / Angiolella, Letizia; Stringaro, Anna Rita; De Bernardis, Flavia; Posteraro, Brunella; Bonito, Mariantonietta; Toccacieli, Laura; Torosantucci, Antonella; Colone, Marisa; Sanguinetti, Maurizio; Cassone, Antonio; Palamara, Anna Teresa.

In: Antimicrobial Agents and Chemotherapy, Vol. 52, No. 3, 03.2008, p. 927-936.

Research output: Contribution to journalArticle

Angiolella, L, Stringaro, AR, De Bernardis, F, Posteraro, B, Bonito, M, Toccacieli, L, Torosantucci, A, Colone, M, Sanguinetti, M, Cassone, A & Palamara, AT 2008, 'Increase of virulence and its phenotypic traits in drug-resistant strains of Candida albicans', Antimicrobial Agents and Chemotherapy, vol. 52, no. 3, pp. 927-936. https://doi.org/10.1128/AAC.01223-07
Angiolella L, Stringaro AR, De Bernardis F, Posteraro B, Bonito M, Toccacieli L et al. Increase of virulence and its phenotypic traits in drug-resistant strains of Candida albicans. Antimicrobial Agents and Chemotherapy. 2008 Mar;52(3):927-936. https://doi.org/10.1128/AAC.01223-07
Angiolella, Letizia ; Stringaro, Anna Rita ; De Bernardis, Flavia ; Posteraro, Brunella ; Bonito, Mariantonietta ; Toccacieli, Laura ; Torosantucci, Antonella ; Colone, Marisa ; Sanguinetti, Maurizio ; Cassone, Antonio ; Palamara, Anna Teresa. / Increase of virulence and its phenotypic traits in drug-resistant strains of Candida albicans. In: Antimicrobial Agents and Chemotherapy. 2008 ; Vol. 52, No. 3. pp. 927-936.
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