Detection of Mutated erg11 and fks1 Genes among Resistant Candida Species Isolated in Pregnant Women in Mbarara, Uganda
Nalumaga Pauline Petra *
Department of Microbiology, Faculty of Medicine, Medical Mycology Unit, Mbarara University of Science and Technology, Mbarara, Uganda.
James Kiguli Mukasa
Department of Microbiology and Immunology, School of Health Sciences, Soroti University, Soroti, Uganda.
Benson Musinguzi
Department of Medical Laboratory Science, Faculty of Health Sciences, Muni University, Arua, Uganda and Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda.
Jude Collins Busingye
Department of Microbiology, Faculty of Medicine, Medical Mycology Unit, Mbarara University of Science and Technology, Mbarara, Uganda.
Daniel Wambua Muasya
Department of Clinical Studies, Faculty of Veterinary Medicine, University of Nairobi, Nairobi, Kenya.
Israel Kiiza Njovu
Department of Microbiology, Faculty of Medicine, Medical Mycology Unit, Mbarara University of Science and Technology, Mbarara, Uganda.
Abraham Birungi
Department of Microbiology, Faculty of Medicine, Medical Mycology Unit, Mbarara University of Science and Technology, Mbarara, Uganda.
Kennedy Kassaza
Department of Microbiology, Faculty of Medicine, Medical Mycology Unit, Mbarara University of Science and Technology, Mbarara, Uganda.
Joel Bazira
Department of Microbiology, Faculty of Medicine, Medical Mycology Unit, Mbarara University of Science and Technology, Mbarara, Uganda.
Herbert Itabangi
Department of Microbiology, Faculty of Medicine, Medical Mycology Unit, Mbarara University of Science and Technology, Mbarara, Uganda and Department of Microbiology and Immunology, Mycology Unit, Busitema University, Mbale, Uganda.
*Author to whom correspondence should be addressed.
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.
Keywords: erg11, fks1, azoles, echinocandins, Candida species