Background
Candida is an opportunistic pathogen that can cause a variety of infections, from superficial to systemic, where the immune system is weakened. It has been suggested that the intestinal tract is a source of Candida infection; however, the role of commensal bacteria and intestinal immunity in Candida colonization in the intestinal tract is unclear. This study aimed to understand the symbiotic relationship between gut bacteria and fungi in people with HIV (PWH).
Methods
A total of 96 PWH with immunological recovery (median CD4 count: 637 cells/μl) were recruited and DNA was extracted from their stools. We identified bacterial and fungal flora by examining bacterial 16S rDNA V3-V4 and fungal ITS1 regions using the MiSeq next-generation sequencer and QIIME2 analysis pipeline. Bacterial extracellular vesicles (BEVs) were isolated from Escherichia coli culture supernatants using ultracentrifugation and size-exclusion chromatography.
Results
Candida were detected in 25% (24/96) of PWH. The undetected group was associated with a higher titer of anti-C. albicans-IgG antibodies in the plasma. The Candida-detected group had significantly higher alpha diversity in the bacterial microbiome than the undetected group, with more short-chain fatty acid (SCFA)-producing Lachnospiraceae and less E. coli. Cell-free supernatant extracted from a laboratory strain of E. coli induced hyphal formation of C. albicans in vitro, while supernatants from Lactobacillus did not show such an effect. Purified BEV from E. coli induced the transactivation of hyphae-specific genes, such as Candida Als3 and Hwp1, and yeast-to-hyphal transition of C. albicans in a few hours.
Conclusions
Our results demonstrate the impact of BEVs secreted from specific commensal bacteria on Candida morphogenesis and clarify one of the mechanisms of Candida intestinal colonization. Normally, the host immune system, particularly soluble IgA, targets and eliminates Candida hyphae; however, under immunocompromised conditions, the hyphal invasion of Candida which has escaped the elimination process may promote systemic candidiasis. The effects of BEVs secreted by commensal bacteria are thought to be varied. Understanding the molecular basis of BEVs in hyphal formation of C. albicans in the intestinal tract may lead to new therapeutic strategies to prevent pathogenic overgrowth of C. albicans.
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