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

Abstract

ABSTRACTThe pathogenesis ofCandida glabratainfections is poorly understood. We studied the pathogenesis of intra-abdominal candidiasis (IAC) in mice that were infected intraperitoneally withC. glabrataand sterile feces.C. glabrataBG2 (5 × 108CFU) caused a 100% mortality rate. Sublethal inocula of BG2 (1 × 108or 1 × 107CFU) caused peritonitis that progressed to abscesses. Three clinicalC. glabratastrains (5 × 108CFU) caused 80 to 100% mortality rates, while a fourth (strain 346) caused a 29% mortality rate. Following sublethal inocula (1 × 107CFU), the intra-abscess burdens of virulent strain 356 were ∼1 log greater than those of strain 346. AC. glabrataΔplb1-2mutant (phospholipase B genes disrupted) killed mice as well as BG2 did. When sublethal inocula were used, however, the Δplb1-2mutant was associated with more rapid abscess resolution and lower intra-abscess burdens; these findings were reversed byPLB1andPLB2reinsertion. The Δplb1-2mutant was also more susceptible than BG2 to killing by human neutrophilsin vitro. BG2 and the Δplb1-2mutant were indistinguishable during hematogenously disseminated candidiasis.C. albicansSC5314 was more virulent thanC. glabrataBG2 during IAC, causing a 100% mortality rate following a challenge with 5 × 107CFU. In contrast, a sublethal inoculum (1 × 107CFU) 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 ofC. glabrataIAC mimics disease in humans and distinguishes the relative virulence of clinical and gene disruption strains.C. glabratadiffered fromC. albicansduring IAC by being less lethal and eliciting dampened neutrophil responses but resulting in more persistent peritonitis and abscesses.