Radiation used for head and neck cancer increases virulence in Candida tropicalis isolated from a cancer patient

Abstract

BackgroundStudies have shown that radiation from radiotherapy increases the yeast colonization of patients. However it is not clear, if such radiation alters the yeast itself. The aim of the present study was therefore to report the direct impact of gamma radiation on Candida tropicalis. Methods C. tropicalis was obtained from a patient with a carcinoma, a suspension of this yeast containing 2.0 × 103 colony forming units per milliliter was prepared. It was submitted to gamma radiation dosage similar to that used in the treatment of head and neck cancer. After a cumulative dose of 7200 cGy some virulence attributes of C. tropicalis, including macro and micromorphological characteristics, adhesion and biofilm abilities, murine experimental infection and phagocytosis resistance were evaluated on irradiated and non-irradiated yeasts.ResultsAfter irradiation the colony morphology of the yeast was altered from a ring format to a smooth appearance in most colonies. Scanning electron microscopy revealed notable differences in the structures of both these colonies and the yeast cells, with the loss of pseudohyphae following irradiation and an increase in extracellular matrix production. The adherence and biofilm production of the yeast was greater following irradiation, both in terms of the number of yeasts and total biomass production on several abiotic surfaces and TR146 cells. The phagocytic index of the irradiated yeasts was not statistically different; however, the presence of cellular debris was detected in the kidneys of infected animals. Mice infected with irradiated yeasts developed an infection at the site of the yeast inoculation, although systemic infection was unchanged.ConclusionsOur findings show for the first time that C. tropicalis, one of the most important yeasts from colonization, which cause fatal candidemia in cancer patients, is affected by gamma irradiation, with changes to its virulence profile.

Candida biofilm production is associated with higher mortality in patients with candidaemia

“…[31][32][33] Furthermore, the adherence and biofilm production of Candida cells on patient mucosa is higher following radiotherapy, both in terms of number of cells and total biomass production, which may be associated with the increased frequency of fungal mucosal infections. 34,35 We observed candidaemia with bacteraemia in 34% of all cases consistent with the previously described data ranging from 6% to 34.5%. 36 Interestingly, the ratio of candidaemia with concomitant bacteraemia was significantly higher for Candida isolates that produced biofilm with low metabolic activity (this was not seen with biofilm mass).…”

“…There is less evidence for an association between fungi and cancer; it was shown that lesions on the oral mucosa have a greater likelihood of undergoing malignant transformation when infected with Candida compared with those that are not infected . Furthermore, the adherence and biofilm production of Candida cells on patient mucosa is higher following radiotherapy, both in terms of number of cells and total biomass production, which may be associated with the increased frequency of fungal mucosal infections …”

Breakdown of Symbiosis in Radiation-Induced Oral Mucositis

“…For instance, during HN RT, the dynamic synchronous variations in the relative abundances of four genera of bacteria ( Fusobacterium , Porphyromonas , Treponema , and Prevotella ) are reportedly related to the onset of high-grade toxicity [ 10 ]. Eventually, the combination of mucosal barrier impairment, hyposalivation, and dysbiosis favors colonization and invasion by fungi ( Figure 1 ) [ 19 , 25 ].…”

“…These new techniques decrease the frequency and intensity of hypo-salivation, reducing the need for dysbiosis-based discontinuation of cancer therapy. Importantly, intensity-modulated RT may reduce the impact of high-dose RT on fungal virulence profile, which was noticed in C. tropicalis [ 25 ].…”

“…The main commensal yeast in the digestive mucosa is Candida albicans, which is responsible for more than 80% of HN infections, followed by C. glabrata and C. tropicalis. [13,25].…”