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Robust, Comprehensive Molecular, and Phenotypical Characterisation of Atypical Candida albicans Clinical Isolates From Bogota, Colombia.

ABSTRACT: Candida albicans is commensal in human microbiota and is known to be the commonest opportunistic pathogen, having variable clinical outcomes that can lead to up to 60% mortality. Such wide clinical behaviour can be attributed to its phenotypical plasticity and high genetic diversity. This study characterised 10 Colombian clinical isolates which had already been identified as C. albicans by molecular tests; however, previous bioinformatics analysis of protein mass spectra and phenotypical characteristics has shown that this group of isolates has atypical behaviour, sharing characteristics of both C. africana and C. albicans. This study was aimed at evaluating atypical isolates' pathogenic capability in the Galleria mellonella model; susceptibility profiles were determined and MLST was used for molecular characterisation. Cluster analysis, enabling unbiased bootstrap to classify the isolates and establish their cluster membership and e-BURST, was used for establishing clonal complexes (CC). Both approaches involved using representative MLST data from the 18 traditional C. albicans clades, as well as C. albicans-associated and minor species. Ten atypical isolates were distributed as follows: 6/10 (B71, B41, B60, R6, R41, and R282) were grouped into a statistically well-supported atypical cluster (AC) and constituted a differentiated CC 6; 2/10 of the isolates were clearly grouped in clade 1 and were concurrent in CC 4 (B80, B44). Another 2/10 atypical isolates were grouped in clade 10 and concurred in CC 7 (R425, R111); most atypical isolates were related to geographically distant isolates and some represented new ST. Isolates B41 and R41 in the AC had greater virulence. Isolate B44 was fluconazole-resistant and was grouped in clade 1. The atypical nature of the isolates studied here was demonstrated by the contrast between phenotypical traits (C. africana-like), molecular markers (C. albicans-like), virulence, and antifungal resistance, highlighting the widely described genetic plasticity for this genus. Our results showed that the atypical isolates forming well-differentiated groups belonged to C. albicans. Our findings could contribute towards developing molecular epidemiology approaches for managing hospital-acquired infection.

SUBMITTER: Rodriguez-Leguizamon G

PROVIDER: S-EPMC7738613 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Robust, Comprehensive Molecular, and Phenotypical Characterisation of Atypical Candida albicans Clinical Isolates From Bogotá, Colombia.

Rodríguez-Leguizamón Giovanni G Ceballos-Garzón Andrés A Suárez Carlos F CF Patarroyo Manuel A MA Parra-Giraldo Claudia M CM

Frontiers in cellular and infection microbiology 20201202

Candida albicans is commensal in human microbiota and is known to be the commonest opportunistic pathogen, having variable clinical outcomes that can lead to up to 60% mortality. Such wide clinical behaviour can be attributed to its phenotypical plasticity and high genetic diversity. This study characterised 10 Colombian clinical isolates which had already been identified as C. albicans by molecular tests; however, previous bioinformatics analysis of protein mass spectra and phenot ...[more]

PMID: 33344263

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Project description:BackgroundCandida albicans remains as the first cause of nosocomial fungal infections in hospitals worldwide and its susceptibility pattern should be better described in our tertiary care hospitals.MethodsThis study aimed at identifying the caspofungin susceptibility pattern regarding nosocomial Candida albicans infection in ten tertiary care hospitals using the methodology proposed by CLSI M27-A3 and CLSI M27-S4, and its association with risk factors and clinical outcome. The approach involved descriptive research concerning the diagnosis of nosocomial infection during a 7-month period in 10 hospitals in Bogotá, Colombia. Associations were established using exact non-parametric statistical tests having a high statistical power (>95%), suitable for small samples. The exact Mann Whitney test or Kruskall-Wallis non-parametric ANOVA tests were used for distributions which were different to normal or ordinal variables when comparing three or more groups. Multivariate analysis involved using binomial, multinomial and ordinal exact logistical regression models (hierarchical) and discrimination power was evaluated using area under the ROC curve.Results101 nosocomial infections were found in 82,967 discharges, for a Candida spp. infection rate of 12.2 per 10,000 discharges, 30.7% caused by C. albicans, 22.8% by C. tropicalis, 20.8% by C. parapsilosis, 19.8% by other Candida, 3% by C. krusei and 3% by C. glabrata. Statistically significant associations between mortality rate and the absence of parenteral nutrition were found in multivariate analysis (OR = 39.746: 1.794-880.593 95% CI: p = 0.020). The model's predictive power was 83.9%, having an 85.9% significant prediction area (69.5%-100 95% CI; p = 0.001).ConclusionsSignificant differences were found regarding susceptibility results when comparing CLSI M27-A3 to CLSI M27-S4 when shifting clinical break-point values. However, one nosocomial strain was consistent in having reduced susceptibility when using both guidelines without having been directly exposed to echinocandins beforehand and no mutations were found in the FKS1 gene for hot spot 1 and/or hot spot 2 regions, thereby highlighting selective pressure regarding widespread antifungal use in tertiary healthcare centres. Nutritional conditions and low family income were seen to have a negative effect on survival rates.

Project description:Resistance to azole antifungals continues to be a significant problem in the common fungal pathogen Candida albicans. Many of the molecular mechanisms of resistance have been defined with matched sets of susceptible and resistant clinical isolates from the same strain. Mechanisms that have been identified include alterations in the gene encoding the target enzyme ERG11 or overexpression of efflux pump genes including CDR1, CDR2, and MDR1. In the present study, a collection of unmatched clinical isolates of C. albicans was analyzed for the known molecular mechanisms of resistance by standard methods. The collection was assembled so that approximately half of the isolates were resistant to azole drugs. Extensive cross-resistance was observed for fluconazole, clotrimazole, itraconazole, and ketoconazole. Northern blotting analyses indicated that overexpression of CDR1 and CDR2 correlates with resistance, suggesting that the two genes may be coregulated. MDR1 overexpression was observed infrequently in some resistant isolates. Overexpression of FLU1, an efflux pump gene related to MDR1, did not correlate with resistance, nor did overexpression of ERG11. Limited analysis of the ERG11 gene sequence identified several point mutations in resistant isolates; these mutations have been described previously. Two of the most common point mutations in ERG11 associated with resistance, D116E and E266D, were tested by restriction fragment length polymorphism analysis of the isolates from this collection. The results indicated that the two mutations occur frequently in different isolates of C. albicans and are not reliably associated with resistance. These analyses emphasize the diversity of mechanisms that result in a phenotype of azole resistance. They suggest that the resistance mechanisms identified in matched sets of susceptible and resistant isolates are not sufficient to explain resistance in a collection of unmatched clinical isolates and that additional mechanisms have yet to be discovered.

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Robust, Comprehensive Molecular, and Phenotypical Characterisation of Atypical Candida albicans Clinical Isolates From Bogota, Colombia.

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Robust, Comprehensive Molecular, and Phenotypical Characterisation of Atypical <i>Candida albicans</i> Clinical Isolates From Bogotá, Colombia.

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