Candida glabrata Intra-Abdominal Candidiasis Is Characterized by Persistence within the Peritoneal Cavity and Abscesses

The pathogenesis of Candida glabrata infections is poorly understood. We studied the pathogenesis of intra-abdominal candidiasis (IAC) in mice that were infected intraperitoneally with C. glabrata and sterile feces. C. glabrata BG2 (5 x 10(8) CFU) caused a 100% mortality rate. Sublethal inocula of BG2 (1 x 10(8) or 1 x 10(7) CFU) caused peritonitis that progressed to abscesses. Three clinical C. glabrata strains (5 x 10(8) CFU) caused 80 to 100% mortality rates, while a fourth (strain 346) caused a 29% mortality rate. Following sublethal inocula (1 x 10(7) CFU), the intra-abscess burdens of virulent strain 356 were similar to 1 log greater than those of strain 346. A C. glabrata Delta plb1-2 mutant (phospholipase B genes disrupted) killed mice as well as BG2 did. When sublethal inocula were used, however, the Delta plb1-2 mutant was associated with more rapid abscess resolution and lower intra-abscess burdens; these findings were reversed by PLB1 and PLB2 reinsertion. The Delta plb1-2 mutant was also more susceptible than BG2 to killing by human neutrophils in vitro. BG2 and the Delta plb1-2 mutant were indistinguishable during hematogenously disseminated candidiasis. C. albicans SC5314 was more virulent than C. glabrata BG2 during IAC, causing a 100% mortality rate following a challenge with 5 x 10(7) CFU. In contrast, a sublethal inoculum (1 x 10(7) CFU) of BG2 caused less neutrophil infiltration and greater burdens in peritoneal fluid than SC5314 did and abscesses that persisted longer and contained greater burdens. In conclusion, a mouse model of C. glabrata IAC mimics disease in humans and distinguishes the relative virulence of clinical and gene disruption strains. C. glabrata differed from C. albicans during IAC by being less lethal and eliciting dampened neutrophil responses but resulting in more persistent peritonitis and abscesses.