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Undesired Effect of Vancomycin Prolonged Treatment: Enhanced Biofilm Production of the Nosocomial Pathogen Candida auris.

ABSTRACT: Fungal infections are often consequent to prolonged antibiotic treatments. Vancomycin (Van) is the first-choice antibiotic in the treatment of Staphylococcus aureus infections associated with colonization of catheter surfaces. We demonstrate the direct effect of Van in promoting the formation of the biofilm of the emergent yeast pathogen Candida auris, developed in the conventional polystyrene microwell plate model, as well as on silicone surfaces (22 and 28% increase in total biomass, respectively) and on an S. aures biofilm, residual after vancomycin treatment, where C. auris achieved 99% of the mixed biofilm population. The effect of Van was assessed also in vivo, in the Galleria mellonella infection model, which showed higher mortality when infected with the yeast pathogen in the presence of the antibiotic. This evidence enhances awareness of the potential risk associated with prolonged antibiotic use in promoting fungal infections.

SUBMITTER: Maione A

PROVIDER: S-EPMC9774269 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Undesired Effect of Vancomycin Prolonged Treatment: Enhanced Biofilm Production of the Nosocomial Pathogen Candida auris.

Maione Angela A Pietra Alessandra La A Salvatore Maria Michela MM Guida Marco M Galdiero Emilia E de Alteriis Elisabetta E

Antibiotics (Basel, Switzerland) 20221208 12

Fungal infections are often consequent to prolonged antibiotic treatments. Vancomycin (Van) is the first-choice antibiotic in the treatment of Staphylococcus aureus infections associated with colonization of catheter surfaces. We demonstrate the direct effect of Van in promoting the formation of the biofilm of the emergent yeast pathogen Candida auris, developed in the conventional polystyrene microwell plate model, as well as on silicone surfaces (22 and 28% increase in total biom ...[more]

PMID: 36551428

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Project description:Candida auris is a recently described pathogenic fungus that is causing invasive outbreaks on all continents. The fungus is of high concern given the numbers of multidrug-resistant strains that have been isolated in distinct sites across the globe. The fact that its diagnosis is still problematic suggests that the spreading of the pathogen remains underestimated. Notably, the molecular mechanisms of virulence and antifungal resistance employed by this new species are largely unknown. In the present work, we compared two clinical isolates of C. auris with distinct drug susceptibility profiles and a Candida albicans reference strain using a multi-omics approach. Our results show that, despite the distinct drug resistance profile, both C. auris isolates appear to be very similar, albeit with a few notable differences. However, compared to C. albicans both C. auris isolates have major differences regarding their carbon utilization and downstream lipid and protein content, suggesting a multifactorial mechanism of drug resistance. The molecular profile displayed by C. auris helps to explain the antifungal resistance and virulence phenotypes of this new emerging pathogen.IMPORTANCECandida auris was first described in Japan in 2009 and has now been the cause of significant outbreaks across the globe. The high number of isolates that are resistant to one or more antifungals, as well as the high mortality rates from patients with bloodstream infections, has attracted the attention of the medical mycology, infectious disease, and public health communities to this pathogenic fungus. In the current work, we performed a broad multi-omics approach on two clinical isolates isolated in New York, the most affected area in the United States and found that the omic profile of C. auris differs significantly from C. albicans In addition to our insights into C. auris carbon utilization and lipid and protein content, we believe that the availability of these data will enhance our ability to combat this rapidly emerging pathogenic yeast.

Project description:Candida auris is an emerging fungal pathogen capable of causing invasive infections in humans. Since its first appearance around 1996, it has been isolated in countries spanning five continents. C. auris is a yeast that has the potential to cause outbreaks in hospitals, can survive in adverse conditions, including dry surfaces and high temperatures, and has been frequently misidentified by traditional methods. Furthermore, strains have been identified that are resistant to two and even all three of the main classes of antifungals currently in use. Several nuclear genome assemblies of C. auris have been published representing different clades and continents, yet until recently, the mitochondrial genomes (mtDNA chromosomes) of this species and the closely related species of C. haemulonii, C. duobushaemulonii, and C. pseudohaemulonii had not been analyzed in depth. We used reads from PacBio and Illumina sequencing to obtain a de novo reference assembly of the mitochondrial genome of the C. auris clade I isolate B8441 from Pakistan. This assembly has a total size of 28.2 kb and contains 13 core protein-coding genes, 25 tRNAs and the 12S and 16S ribosomal subunits. We then performed a comparative analysis by aligning Illumina reads of 129 other isolates from South Asia, Japan, South Africa, and South America with the B8441 reference. The clades of the phylogenetic tree we obtained from the aligned mtDNA sequences were consistent with those derived from the nuclear genome. The mitochondrial genome revealed a generally low genetic variation within clades, although the South Asian clade displayed two sub-branches including strains from both Pakistan and India. In particular, the 86 isolates from Colombia and Venezuela had mtDNA sequences that were all identical at the base level, i.e., a single conserved haplotype or mitochondrial background that exhibited characteristic differences from the Pakistan reference isolate B8441, such as a unique 25-nt insert that may affect function.

Dataset Information

Undesired Effect of Vancomycin Prolonged Treatment: Enhanced Biofilm Production of the Nosocomial Pathogen Candida auris.

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Undesired Effect of Vancomycin Prolonged Treatment: Enhanced Biofilm Production of the Nosocomial Pathogen <i>Candida auris</i>.

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