Genetic diversity and antifungal susceptibilities of environmental Cryptococcus neoformansand Cryptococcus gattiispecies complexes

Cryptococcosis is an opportunistic systemic mycosis caused by Cryptococcus neoformansand C. gattiispecies complexes and is of increasing global importance. Maintaining continued surveillance of the antifungal susceptibility of environmental C. neoformansand C. gattiiisolates is desirable for better managing cryptococcosis by identifying resistant isolates and revealing the emergence of intrinsically resistant species. Relevant research data from Egypt are scarce. Thus, this study aimed to report the genetic diversity of C. neoformansand C. gattiispecies complexes originating from different environmental sources in Egypt, antifungal susceptibility profiles, antifungal combinations, and correlations of susceptibility with genotypes. A total of 400 environmental samples were collected, 220 from birds and 180 from trees. Cryptococcusspp. were found in 58 (14.5%) of the samples, 44 (75.9%) of the isolates were recovered from birds and 14 (24.1%) from trees. These isolates were genotyped using M13 polymerase chain reaction-fingerprinting and URA5 gene restriction fragment length polymorphism analysis. Of the 31 C. neoformansisolates, 24 (77.4%), 6 (19.4%) and one (4.4%) belonged to VNI, VNII, and VNIII genotypes, respectively. The 27 C. gattiiisolates belonged to VGI (70.4%), VGII (18.5%), and VGIII (11.1%) genotypes. Non-wild type C. neoformansand C. gattiiisolates that may have acquired resistance to azoles, amphotericin B (AMB), and terbinafine (TRB) were observed. C. gattiiVGIII was less susceptible to fluconazole (FCZ) and itraconazole (ITZ) than VGI and VGII. C. neoformansisolates showed higher minimum inhibitory concentrations (MICs) to FCZ, ITZ, and voriconazole (VRZ) than those of C. gattiiVGI and VGII. Significant (P< 0.001) correlations were found between the MICs of VRZ and ITZ (r= 0.64) in both C. neoformansand C. gattiiisolates, FCZ and TRB in C. neoformansisolates, and FCZ and TRB (r= 0.52) in C. gattiiisolates.