Candida parapsilosis Mdr1B and Cdr1B Are Drivers of Mrr1-Mediated Clinical Fluconazole Resistance

Doorley, Laura A.; Rybak, Jeffrey M.; Zhang, Qing; Morschhäuser, Joachim; Rogers, P. David

doi:10.1128/aac.00289-22

Cited by 12 publications

(21 citation statements)

References 33 publications

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“…Independently from increased copy number, overexpression of CDR1B in the resistant isolate CPS-C and in MRR1 RI clone, expressing the GOF MRR1 allele, was observed. This strongly suggests that expression of CDR1B gene is regulated by MRR1 transcription factor as suggested by Doorley et al (8). Interestingly, the CDR1 (CLUG_03113) expression in C. lusitaniae was also shown to be regulated by GOF mutation in MRR1 (15).…”

Section: Discussionmentioning

confidence: 63%

“…However, CPAR2_304370 has approximately 15 copies in CPS-B compared to 4 copies found in CPS-A and CPS-C. CPAR2_304370 is a member of the Cdr1 multidrug transporters, recently named CDR1B in C. parapsilosis (8). The increase in the copy number of CDR1B in CPS-B is correlated with an increase in expression of approximately 9,5-fold of CDR1B in comparison to isolate CPS-A (Figure 1).…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 95%

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Clinical azole cross-resistance in Candida parapsilosis is related to a novel MRR1 gain-of-function mutation

Branco

Ryan

Silva

et al. 2022

Clinical Microbiology and Infection

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Section: Discussionmentioning

confidence: 63%

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 95%

Clinical azole cross-resistance in Candida parapsilosis is related to a novel MRR1 gain-of-function mutation

Branco

Ryan

Silva

et al. 2022

Clinical Microbiology and Infection

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“…C. parapsilosis isolates share a common antimicrobial profile in which the high MIC to fluconazole (FLU > 256 mg/L) stands out. Azole resistance in C. parapsilosis is well documented, being at the molecular level associated with two multidrug transporters (Cdr1 and Mdr1) and an enzyme involved in ergosterol biosynthesis (lanosterol 14α-demethylase coded by the ERG11 gene) [ 27 , 28 , 29 ].…”

Section: Resultsmentioning

confidence: 99%

Antimicrobial Resistance and Biofilms Underlying Catheter-Related Bloodstream Coinfection by Enterobacter cloacae Complex and Candida parapsilosis

et al. 2022

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Biofilm-associated infections are a public health concern especially in the context of healthcare-associated infections such as catheter-related bloodstream infections (CRBSIs). We evaluated the biofilm formation and antimicrobials resistance (AMR) of Enterobacter cloacae complex and Candida parapsilosis co-isolated from a CRBSI patient. Antimicrobial susceptibility of central venous catheters (CVCs) and hemoculture (HC) isolates was evaluated, including whole genome sequencing (WGS) resistome analysis and evaluation of gene expression to obtain insight into their AMR determinants. Crystal violet assay was used to assess dual biofilm biomass and microscopy was used to elucidate a microorganism’s distribution within biofilms assembled on different materials. Bacteria were multidrug-resistant including resistance to colistin and beta-lactams, likely linked to the mcr-9-like phosphoethanolamine transferase and to an ACT family cephalosporin-hydrolyzing class C beta-lactamase, respectively. The R398I and Y132F mutations in the ERG11 gene and its differential expression might account for C. parapsilosis resistance to fluconazole. The phenotype of dual biofilms assembled on glass, polystyrene and polyurethane depends on the material and how biofilms were initiated by one or both pathogens. Biofilms assembled on polyurethane were denser and richer in the extracellular polymeric matrix, and microorganisms were differently distributed on the inner/outer surface of the CVC.

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“…Recently, researchers described a new azole resistance mechanism in Candida , particularly among C. parapsilosis isolates, involving another Cdr1-like gene, the CDR1B (CPAR2_304370). Expression of a GOF mutation in the MRR1 gene impacts the fluconazole susceptibility in C. parapsilosis through CDR1B overexpression [ 114 , 127 ]. CDR1 (CLUG_03113) expression in Candida lusitaniae is also shown to be regulated by GOF mutation in MRR1 [ 128 ].…”

Section: Antifungals and Resistance Mechanismsmentioning

confidence: 99%

Candida parapsilosis Virulence and Antifungal Resistance Mechanisms: A Comprehensive Review of Key Determinants

Branco

Miranda

Rodrigues

2023

JoF

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Candida parapsilosis is the second most common Candida species isolated in Asia, Southern Europe, and Latin America and is often involved in invasive infections that seriously impact human health. This pathogen is part of the psilosis complex, which also includes Candida orthopsilosis and Candida metapsilosis. C. parapsilosis infections are particularly prevalent among neonates with low birth weights, individuals who are immunocompromised, and patients who require prolonged use of a central venous catheter or other indwelling devices, whose surfaces C. parapsilosis exhibits an enhanced capacity to adhere to and form biofilms. Despite this well-acknowledged prevalence, the biology of C. parapsilosis has not been as extensively explored as that of Candida albicans. In this paper, we describe the molecular mechanistic pathways of virulence in C. parapsilosis and show how they differ from those of C. albicans. We also describe the mode of action of antifungal drugs used for the treatment of Candida infections, namely, polyenes, echinocandins, and azoles, as well as the resistance mechanisms developed by C. parapsilosis to overcome them. Finally, we stress the importance of the ongoing search for species-specific features that may aid the development of effective control strategies and thus reduce the burden on patients and healthcare costs.

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Candida parapsilosis Mdr1B and Cdr1B Are Drivers of Mrr1-Mediated Clinical Fluconazole Resistance

Cited by 12 publications

References 33 publications

Clinical azole cross-resistance in Candida parapsilosis is related to a novel MRR1 gain-of-function mutation

Clinical azole cross-resistance in Candida parapsilosis is related to a novel MRR1 gain-of-function mutation

Antimicrobial Resistance and Biofilms Underlying Catheter-Related Bloodstream Coinfection by Enterobacter cloacae Complex and Candida parapsilosis

Candida parapsilosis Virulence and Antifungal Resistance Mechanisms: A Comprehensive Review of Key Determinants

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