A Candida albicans strain with high MIC for caspofungin and no FKS1 mutations exhibits a high chitin content and mutations in two chitinase genes.
We studied the cell wall of a Candida albicans laboratory mutant exhibiting a high minimum inhibitory concentration (MIC; 8 μg ml(-1)) for caspofungin without bearing FKS1 mutations. This strain showed a reduced level of ß 1,3 D glucan (0.43×) and a higher chitin content (2.3×) than a control strain even when grown without caspofungin. No significant over- or under-expression of chitin synthase or chitinase genes was observed. However, point mutations were detected in the chitinase 2 and 3 genes. These mutations, which may affect the enzymatic activity of the encoded protein products involved in the degradation of the chitin, could have led to an increased concentration of that component, allowing the strain to compensate for its low ß 1,3 D glucan content and the effect of caspofungin.
UMR 145 IRD/UM1: VIH/SIDA et Maladies Associées, UFR des Sciences Pharmaceutiques et Biologiques, Montpellier Cedex, France.
P
P
Drakulovski
C
C
Dunyach
S
S
Bertout
J
J
Reynes
M
M
Mallié
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D000077336:Caspofungin; D002473:Cell Wall / Q000737:chemistry; D002686:Chitin / Q000378:metabolism*; D002688:Chitinases / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000494:pharmacology*; D005656:Fungal Proteins / Q000235:genetics; D005964:Glucosyltransferases / Q000235:genetics; D006801:Humans; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D011509:Proteoglycans; D047071:beta-Glucans / Q000032:analysis
D000935:Antifungal Agents; D054714:Echinocandins; D005656:Fungal Proteins; D055666:Lipopeptides; D050505:Mutant Proteins; D011509:Proteoglycans; D047071:beta-Glucans; D002686:Chitin; C010770:polysaccharide-K; D005964:Glucosyltransferases; D002688:Chitinases; D000077336:Caspofungin