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ABSTRACTCandida albicansis a normal member of the gastrointestinal (GI) tract microbiota of healthy humans, but during host immunosuppression or alterations in the bacterial microbiota, C. albicanscan disseminate and cause life-threatening illness. The bacterial microbiome of the GI tract, including lactic acid bacteria (LAB), plays a vital role in preventing fungal invasion. However, little is known about the role of C. albicansin shaping the bacterial microbiota during antibiotic recovery. We investigated the fungal burdens in the GI tracts of germfree mice and mice with a disturbed microbiome to demonstrate the role of the microbiota in preventing C. albicanscolonization. Histological analysis demonstrated that colonization with C. albicansduring antibiotic treatment does not trigger overt inflammation in the murine cecum. Bacterial diversity is reduced long term following cefoperazone treatment, but the presence of C. albicansduring antibiotic recovery promoted the recovery of bacterial diversity. Cefoperazone diminishes Bacteroidetespopulations long term in the ceca of mice, but the presence of C. albicansduring cefoperazone recovery promoted Bacteroidetespopulation recovery. However, the presence of C. albicansresulted in a long-term reduction in Lactobacillusspp. and promoted Enterococcus faecalispopulations. Previous studies have focused on the ability of bacteria to alter C. albicans; this study addresses the ability of C. albicansto alter the bacterial microbiota during nonpathogenic colonization.

ABSTRACTThe indigenous bacterial microbiome of the stomach, including lactobacilli, is vital in promoting colonization resistance against Candida albicans. However, there are gaps in our understanding about C. albicansgastric colonization versus disease, especially during the postantibiotic recovery phase. This study compared the gastric responses to C. albicansstrains CHN1 and SC5314 in microbiome-disturbed and germfree mice to elucidate the contribution of the indigenous microbiota in C. albicanscolonization versus disease and yeast-bacterium antagonism during the post-cefoperazone recolonization period. C. albicanscan prevent the regrowth of Lactobacillusspp. in the stomach after cefoperazone and promote increased colonization by Enterococcusspp. Using a culture-independent analysis, the effects of oral cefoperazone on the gastric bacterial microbiota were observed to last at least 3 weeks after the cessation of the antibiotic. Disturbance of the gastric bacterial community by cefoperazone alone was not sufficient to cause gastritis, C. albicanscolonization was also needed. Gastritis was not evident until after day 7 in cefoperazone-treated infected mice. In contrast, in germfree mice which lack a gastric microbiota, C. albicansinduced gastric inflammation within 1 week of inoculation. Therefore, the gastric bacterial community in cefoperazone-treated mice during the first week of postantibiotic recolonization was sufficient to prevent the development of gastritis, despite being ineffective at conferring colonization resistance against C. albicans. Altogether, these data implicate a dichotomy between C. albicanscolonization and gastric disease that is bacterial microbiome dependent.

The indigenous bacterial microbiome of the stomach, including lactobacilli, is vital in promoting colonization resistance against Candida albicans. However, there are gaps in our understanding about C. albicans gastric colonization versus disease, especially during the postantibiotic recovery phase. This study compared the gastric responses to C. albicans strains CHN1 and SC5314 in microbiome-disturbed and germfree mice to elucidate the contribution of the indigenous microbiota in C. albicans colonization versus disease and yeast-bacterium antagonism during the post-cefoperazone recolonization period. C. albicans can prevent the regrowth of Lactobacillus spp. in the stomach after cefoperazone and promote increased colonization by Enterococcus spp. Using a culture-independent analysis, the effects of oral cefoperazone on the gastric bacterial microbiota were observed to last at least 3 weeks after the cessation of the antibiotic. Disturbance of the gastric bacterial community by cefoperazone alone was not sufficient to cause gastritis, C. albicans colonization was also needed. Gastritis was not evident until after day 7 in cefoperazone-treated infected mice. In contrast, in germfree mice which lack a gastric microbiota, C. albicans induced gastric inflammation within 1 week of inoculation. Therefore, the gastric bacterial community in cefoperazone-treated mice during the first week of postantibiotic recolonization was sufficient to prevent the development of gastritis, despite being ineffective at conferring colonization resistance against C. albicans. Altogether, these data implicate a dichotomy between C. albicans colonization and gastric disease that is bacterial microbiome dependent.

Candida albicans produces lipid metabolites that are functionally similar to host prostaglandins. These studies, using mass spectrometry, demonstrate that C. albicans produces authentic prostaglandin E2(PGE2) from arachidonic acid. Maximal PGE2production was achieved at 37°C in stationary-phase culture supernatants and in cell-free lysates generated from stationary-phase cells. Interestingly, PGE2production is inhibited by both nonspecific cyclooxygenase and lipoxygenase inhibitors but not by inhibitors specific for the cyclooxygenase 2 isoenzyme. The C. albicans genome does not possess a cyclooxygenase homolog; however, several genes that may play a role in prostaglandin production from C. albicans were investigated. It was found that a C. albicans fatty acid desaturase homolog (Ole2) and a multicopper oxidase homolog (Fet3) play roles in prostaglandin production, with ole2/ole2 and fet3/fet3 mutant strains exhibiting reduced PGE2levels compared with parent strains. This work demonstrates that the synthesis of PGE2in C. albicans proceeds via novel pathways.