Detection of Mutated erg11 and fks1 Genes among Resistant Candida Species Isolated in Pregnant Women in Mbarara, Uganda

Abstract

Background:  Vulvovaginal candidiasis is estimated to range between 35-60% among pregnant women worldwide. The emergency of anti-fungal resistance in Candida species against azoles and caspofungin is a rising concern because there is a limited range of choices of antifungals to be used in pregnant women with low toxicity. In Uganda, the burden of vulvovaginal candidiasis is estimated to be 48%. However, there is limited data regarding in vitro phenotypic and genotypic anti-fungal susceptibility patterns among candida species isolated from pregnant women. Thus, this study aimed to screen for the two mutated famous erg11 and fks1 genes that lead to anti-fungal resistance among clinical candida isolates. Methods: A cross-sectional study involving 90 Candida species isolates previously collected from a larger study carried out from Mbarara regional referral hospital. Phenotypic susceptibility methods (Kirby-Bauer and minimum inhibitory concentration) while Polymerase chain reaction method and gel electrophoresis were used for detection of the amplified mutated ERG11 and FKS1 genes. Mean and chi-square tests were used to evaluate the associations of resistance patterns between resistant and susceptible isolates. Results: Out of the 90 Candida isolates recovered, 56% were Candida albicans, C.glabrata were 31.11% (28/90), C. parapsilosis and C.famata accounted for 4.44% (4/90) each, C. krusei accounted for 3.33% (3/90) while C. tropicalis accounted for 1.11% (1/90). All the Candida isolates were susceptible to caspofungin while fluconazole resistance was 34.4%. The FKS1 mutated gene was not detected in randomly selected caspofungin susceptible isolates. The ERG11 mutated gene was detected in 80.6% of the fluconazole-resistant isolates and 87.5% of the isolates with intermediate activity towards fluconazole.  Conclusion: This study provides evidence that mutated erg11 gene causes reduced fluconazole drug susceptibility (p-value 0.001). Susceptible dose dependence should not be ignored as it may be associated with ERG11 gene mutation leading to resistance to fluconazole.