Multiple Candida strains in the course of a single systemic infection.

Species and strain variabilities have been monitored during the history of a prolonged Candida infection in a single compromised bone marrow transplant patient by analyzing sugar assimilation patterns, high-frequency switching repertoires, and Southern blot hybridization patterns with two cloned mid-repeat sequences (Ca3 and Ca7) which are species specific for Candida albicans and one cloned mid-repeat sequence (Ct13-8) which is species specific for Candida tropicalis. Evidence is presented that during the course of this infection (i) two strains of C. albicans and three strains of C. tropicalis were distinguished by their switching repertoires, Southern blot hybridization patterns, and sugar assimilation patterns; (ii) the three C. tropicalis strains were in a high-frequency mode of switching; (iii) two C. tropicalis strains coexisted in the blood and three C. tropicalis strains coexisted in the throat at different times during the history of the infection; (iv) amphotericin B treatment selectively removed one of two C. tropicalis strains coexisting in the blood and this strain exhibited greater susceptibility to amphotericin B in vitro (the remaining strain was subsequently removed from the blood by flucytosine treatment); and (v) both the strain removed from the blood by amphotericin B and the strain removed from the blood by flucytosine reappeared several days later at another site of infection. It is demonstrated for the first time that C. tropicalis is capable of high-frequency switching of colony morphology just as C. albicans is, that there is more than one strain-specific switching repertoire in C. tropicalis, and that a C. tropicalis mid-repeat sequence can be used for discriminating species and assessing strain relatedness, as previously demonstrated for C. albicans mid-repeat sequences.