Oral Fungal Infections: Past, Present, and Future

Abstract

Oral fungal infections have afflicted humans for millennia. Hippocrates (ca. 460-370 BCE) described two cases of oral aphthae associated with severe underlying diseases that could well have been oral candidiasis. While oral infections caused by other fungi such as cryptococcosis, aspergillosis, mucormycosis, histoplasmosis, blastomycosis, and coccidioidomycosis occur infrequently, oral candidiasis came to the fore during the AIDS epidemic as a sentinel opportunistic infection signaling the transition from HIV infection to AIDS. The incidence of candidiasis in immunocompromised AIDS patients highlighted the importance of host defenses in preventing oral fungal infections. A greater understanding of the nuances of human immune systems has revealed that mucosal immunity in the mouth delivers a unique response to fungal pathogens. Oral fungal infection does not depend solely on the fungus and the host, however, and attention has now focussed on interactions with other members of the oral microbiome. It is evident that there is inter-kingdom signaling that affects microbial pathogenicity. The last decade has seen significant advances in the rapid qualitative and quantitative analysis of oral microbiomes and in the simultaneous quantification of immune cells and cytokines. The time is ripe for the application of machine learning and artificial intelligence to integrate more refined analyses of oral microbiome composition (including fungi, bacteria, archaea, protozoa and viruses—including SARS-CoV-2 that causes COVID-19). This analysis should incorporate the quantification of immune cells, cytokines, and microbial cell signaling molecules with signs of oral fungal infections in order to better diagnose and predict susceptibility to oral fungal disease.

Magnolol as a potent antifungal agent inhibits Candida albicans virulence factors via the PKC and Cek1 MAPK signaling pathways

“…Oral candidiasis, one of the most common opportunistic infections, caused mainly by Candida albicans, has seen a significant increase in prevalence due in part to the widespread application of broad-spectrum antibiotics, immunosuppressants, and glucocorticoids. Long-term oral candidiasis can lead to severe deep fungal infections, even inducing cancer and endangering life (Cannon, 2022). The mortality rate of invasive candidiasis can reach 40-60% (McCarty et al, 2021).…”

Marine Compounds with Anti-Candida sp. Activity: A Promised “Land” for New Antifungals

“…However, in the last decade, the non- Candida albicans Candida species (NCACs) (e.g., Candida glabrata , Candida krusei , Candida tropicalis , or Candida parapsilosis ) have been escalating due to the widespread use and even overuse of broad-spectrum antimicrobial drugs. In addition, and more alarmingly, NCACs have been linked to high rates of antifungal resistance and chronic infections [ 1 , 2 , 3 ].…”

Candida Carriers among Individuals with Tongue Piercing—A Real-Time PCR Study

“…Oral fungal infection does not depend solely on the fungus and the host, however, and attention has now focused on interactions with other members of the oral microbiome. It is evident that there is inter-kingdom signaling that affects microbial pathogenicity [ 1 ]. When the oral eubiosis is altered, the dynamic and polymicrobial oral microbiome could be a direct precursor of different diseases including oral candidiasis.…”