Genetic and phenotypic characterization of Candida albicans strains isolated from infectious disease patients in Shanghai

Abstract

Candida albicans, as an opportunistic pathogen, can cause superficial and life-threatening candidiasis in immunocompromised individuals. The formation of surface-associated biofilms and the appearance of drug resistance pose a significant challenge for clinical intervention. In this study, a total of 104 hospital-acquired C. alibcans clinical isolates were collected from sterile sites and mucosal lesions of 92 infectious disease patients in the Shanghai Public Health Clinical Center and analysed. The resistance rates to fluconazole, itraconazole and voriconazole were 12.5 %, 15.4 % and 11.5 % respectively. Multilocus sequence typing (MLST) analysis identified 63 diploid sequence types (DSTs) with a decentralized phylogeny, of which 37 DSTs (58.7 %) had not been reported in the online MLST database. Loss of heterozygosity was observed in ACC1 and ADP1 sequences obtained from six sequential isolates from a patient receiving antifungal treatment, which exemplified the effect of microevolution on C. albicans genetic alterations. Biofilm formation capability, an important virulence trait of C. albicans, was variable among strains isolated from different anatomical sites (P50.0302) and affected by genotypes (P50.0185). The mRNA levels of the azole antifungal target ERG11 gene and efflux pump genes (CDR1, CDR2 and MDR1) were detected in 9-18.1 % of azole-resistant and susceptible-dose dependent (S-DD) isolates. Twelve mutations encoding distinct amino acid substitutions in ERG11 were found in azoleresistant and S-DD isolates. Among them, A114S, Y132H and Y257H substitution in the ERG11 gene may be primarily related to azole resistance. Taken together, we observed a high level of diversity within C. albicans isolates. Multiple inter-related underlying mechanisms, including genetic and environmental factors, may account for high surface adhesion or azole resistance in clinical C. albicans infections.Abbreviations: AAT1, aspartate aminotransferase; ACC1, Acetyl-coenzyme A carboxylase; ACT1, actin; ADP1, ATP-dependent permease; ALS, hyphaspecific surface protein; BSI, nosocomial bloodstream infection; CDR1, CDR2, ATP-dependent efflux pumps; CLSI, Clinical and Laboratory Standard Institute; DST, diploid sequence type; ERG11, cytochrome P450 14a-demethylase; HWP1, hypha-specific cell wall protein; MDR1, major facilitator pump; MLST, multilocus sequence typing; MPI, mannose phosphate isomerase; SAP, secreted aspartyl protease; S-DD, susceptible-dose dependent; SYA1, alanyl-RNA synthetase; VPS13, vacuolar protein sorting protein; XTT, 2,3-bis-(2-methoxy-4-nitro-5-sulphenyl)-2H-tetrazolium-5-carboxanilide; YPD, yeast extract, peptone, dextrose medium; ZWF1b, glucose-6-phosphate dehydrogenase.

Interactions between Candida albicans and Candida glabrata in biofilms: Influence of the strain type, culture medium and glucose supplementation

“…Nevertheless, in mixed biofilms, the total biomass may differ from that found for each single biofilm, depending on the type of relationship established between the microorganisms, as demonstrated in the present study. Rossoni et al used only reference strains to evaluate the interactions among C. albicans , C. krusei and C. glabrata , and emphasised the importance of the use of clinical isolates, since previous studies have demonstrated intra‐species variability for clinical strains of Candida in relation to the capacity of biofilm formation and pathogenicity in animal models . Also, Pathak et al found higher biofilm production (24 hours) by C. glabrata on acrylic surfaces when compared to C. albicans , with a higher biomass when these species were associated .…”

Mixed biofilms formed by C. albicans and non-albicans species: a study of microbial interactions

“…Previous studies demonstrated that the clinical isolates of Candida exhibit intraspecies variability in relation to biofilm forming ability. 29,30 Muadcheingka and Tantivitayakul 31 evaluated the cell surface hydrophobicity (CSH) of 250 clinical isolates from oral candidiasis. CSH is an intrinsic property of the external cell wall layer of Candida; it promotes strong binding and irreversible adherence to the mucosal membrane or other substrates, contributing to biofilm formation.…”

Detection The Prevalence of Adhesins and Extracellular hydrolytic enzymes genes in Candida albicans Biofilm Formation

“…Biofilm formation by C. albicans has shown to be highly variable and is directly associated with pathogenicity and poor clinical outcomes in patients at risk [34]. Biofilm formation was variable among C. albicans strains that were isolated from different anatomical sites [35].…”