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Antifungal susceptibility pattern and biofilm-related genes expression in planktonic and biofilm cells of Candida parapsilosis species complex.

ABSTRACT: Background and Purpose:Candida parapsilosis complex isolates are mainly responsible for nosocomial catheter-related infection in immunocompromised patients. Biofilm formation is regarded as one of the most pertinent key virulence factors in the development of these emerging infections. The present study aimed to compare in vitro antifungal susceptibility patterns and biofilm-related genes expression ratio in planktonic and biofilm's cells of clinically C. parapsilosis complex isolates. Materials and Methods:The current study was conducted on a number of 17 clinical C. parapsilosis complex (10 C. parapsilosis sensu stricto, 5 C. orthopsilosis, and 2 C. metapsilosis). The antifungal susceptibility patterns of amphotericin B, ?uconazole, itraconazole, voriconazole, posaconazole, and caspofungin in planktonic and biofilm forms were closely examined using CLSI M27-A3 broth microdilution method. The expression levels of biofilm-related genes (BCR1, EFG1, and FKS1) were evaluated in planktonic and biofilm's cells using Real-time polymerase chain reaction (PCR) technique. Results:The obtained results indicated that all C. parapsilosis complex isolates were able to produce high and moderate amounts of biofilm forms. In addition, the sessile minimum inhibitory concentrations were reported to be high for fluconazole (? 64 µg/ml), itraconazole, voriconazole, and posaconazole (? 16 µg/ml), as compared to planktonic minimum inhibitory concentrations. Moreover, a significant difference was observed between antifungal susceptibility patterns for all azole antifungal agents (P<0.05). Furthermore, the BCR1 overexpression was considered significant in biofilms with regard to planktonic cells in C. parapsilosis species complex (P=0.002). Conclusion:C. parapsilosis complex isolates were found susceptible to most of the tested antifungal drugs, while biofilms demonstrated a noticeable resistant to azoles. The marked discrepancy noted in antifungal susceptibility patterns among these species should be highlighted to achieve effective therapeutic treatment.

SUBMITTER: Modiri M

PROVIDER: S-EPMC7034785 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Antifungal susceptibility pattern and biofilm-related genes expression in planktonic and biofilm cells of <i>Candida parapsilosis</i> species complex.

Modiri Mona M Hashemi Seyed Jamal SJ GhazvinI Roshanak Daie RD Khodavaisy Sadegh S Ahmadi Ali A Ghaffari Mansoureh M Rezaie Sassan S

Current medical mycology 20190101 4

<h4>Background and purpose</h4><i>Candida parapsilosis</i> complex isolates are mainly responsible for nosocomial catheter-related infection in immunocompromised patients. Biofilm formation is regarded as one of the most pertinent key virulence factors in the development of these emerging infections. The present study aimed to compare <i>in vitro</i> antifungal susceptibility patterns and biofilm-related genes expression ratio in planktonic and biofilm's cells of clinically <i>C. parapsilosis</i ...[more]

PMID: 32104742

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Project description:Candida parapsilosis complex is one of the most common non-albicans Candida species that cause candidemia, especially invasive candidiasis. The purpose of this study was to evaluate the antifungal susceptibilities of both colonized and invasive clinical C. parapsilosis complex isolates to 10 drugs: amphotericin (AMB), anidulafungin (AFG), caspofungin (CAS), micafungin (MFG), fluconazole (FLZ), voriconazole (VRZ), itraconazole (ITZ), posaconazole (POZ), 5-flucytosine (FCY), and isaconazole (ISA). In total, 884 C. parapsilosis species complex isolates were gathered between January 2005 and December 2020. C. parapsilosis, Candida metapsilosis, and Candida orthopsilosis accounted for 86.3, 8.1, and 5.5% of the cryptic species, respectively. The resistance/non-wild-type rate of bloodstream C. parapsilosis to the drugs was 3.5%, of C. metapsilosis to AFG and CAS was 7.7%, and of C. orthopsilosis to FLZ and VRZ was 15% and to CAS, MFG, and POZ was 5%. The geometric mean (GM) minimum inhibitory concentrations (MICs) of non-bloodstream C. parapsilosis for CAS (0.555 mg/L), MFG (0.853 mg/L), FLZ (0.816 mg/L), VRZ (0.017 mg/L), ITZ (0.076 mg/L), and POZ (0.042 mg/L) were significantly higher than those of bloodstream C. parapsilosis, for which the GM MICs were 0.464, 0.745, 0.704, 0.015, 0.061, and 0.033 mg/L, respectively (P < 0.05). The MIC distribution of the bloodstream C. parapsilosis strains collected from 2019 to 2020 for VRZ, POZ, and ITZ were 0.018, 0.040, and 0.073 mg/L, significantly higher than those from 2005 to 2018, which were 0.013, 0.028, and 0.052 mg/L (P < 0.05). Additionally, MIC distributions of C. parapsilosis with FLZ and the distributions of C. orthopsilosis with ITZ and POZ might be higher than those in Clinical and Laboratory Standards Institute studies. Furthermore, a total of 143 C. parapsilosis complex isolates showed great susceptibility to ISA. Overall, antifungal treatment of the non-bloodstream C. parapsilosis complex isolates should be managed and improved. The clinicians are suggested to pay more attention on azoles usage for the C. parapsilosis complex isolates. In addition, establishing the epidemiological cutoff values (ECVs) for azoles used in Eastern China may offer better guidance for clinical treatments. Although ISA acts on the same target as other azoles, it may be used as an alternative therapy for cases caused by FLZ- or VRZ-resistant C. parapsilosis complex strains.

Project description:Candida haemulonii, Candida haemulonii var. vulnera and Candida duobushaemulonii, which form the C. haemulonii complex, are emerging etiologic agents of fungal infections known to be resistant to the most commonly used antifungals. The well-established anti-Candida potential of metal complexes containing 1,10-phenanthroline (phen) ligands encouraged us to evaluate different copper(II), manganese(II), and silver(I) phen chelates for their ability to inhibit planktonic growth and biofilm of C. haemulonii species complex. Two novel coordination complexes, {[Cu(3,6,9-tdda)(phen)2].3H2O.EtOH}n and [Ag2(3,6,9-tdda)(phen)4].EtOH (3,6,9-tddaH2 = 3,6,9-trioxaundecanedioic acid), were synthesized in a similar fashion to the other, previously documented, sixteen copper(II), manganese(II), and silver(I) chelates employed herein. Three isolates of each C. haemulonii species complex were used and the effect of the metal chelates on viability was determined utilizing the CLSI standard protocol and on biofilm-growing cells using the XTT assay. Cytotoxicity of the chelates was evaluated by the MTT assay, employing lung epithelial cells. The majority of the metal chelates were capable of interfering with the viability of planktonic-growing cells of all the fungal isolates. The silver complexes were the most effective drugs (overall geometric mean of the minimum inhibitory concentration (GM-MIC) ranged from 0.26 to 2.16 ?M), followed by the manganese (overall GM-MIC ranged from 0.87 to 10.71 ?M) and copper (overall GM-MIC ranged from 3.37 to >72 ?M) chelates. The manganese chelates (CC50 values ranged from 234.51 to >512 ?M) were the least toxic to the mammalian cells, followed by the silver (CC50 values ranged from 2.07 to 13.63 ?M) and copper (CC50 values ranged from 0.53 to 3.86 ?M) compounds. When tested against mature biofilms, the chelates were less active, with MICs ranging from 2- to 33-fold higher levels when compared to the planktonic MIC counterparts. Importantly, manganese(II), copper(II), and silver(I) phen chelates are relatively cheap and easy to synthesize and they offer significant antifungal chemotherapeutic potential for the treatment of highly resistant pathogens.

Project description:Background and purposeOpportunistic fungal infections have been on a growing trend since the last two decades. Among the opportunistic fungal agents, Candida species, Cryptococcus neoformans, and Aspergillus fumigatus account for most of the life-threatening infections in immunocompromised individuals. Regarding this, the present study aimed to investigate the molecular identification and antifungal susceptibility pattern of Candida species isolated from HIV-infected patients.Materials and methodsThis study was conducted on 80 clinical samples collected from HIV-infected patients with suspected candidiasis referring to Tagore Medical College and Hospital, Rathinamangalam and Government Hospital of Thoracic Medicine, in Chennai, India, for 18 months (i.e., May 2016-December 2017). Phenotypic and molecular identification was accomplished using internal transcribed spacer region 1 (ITS1) and ITS4 primers. The antifungal susceptibility pattern of the isolates against four antifungal agents was also determined by both disk diffusion and broth dilution methods.ResultsIn the present study, the prevalence of candidiasis was obtained as 75% (n=60). Candida tropicalis was the predominant identified species. All the emerging species (i.e., Kodamaea ohmeri, Hanseniaspora opuntiae, and C. orthopsilosis) were identified through molecular identification since the phenotypic identification was inconclusive. In terms of the susceptibility pattern, 63.3% and 18.3% of the isolates were resistant to fluconazole and voriconazole, respectively. Candida albicans was also found to be resistant to amphotericin B.ConclusionMolecular assay led to the identification of K. ohmeri, H. opuntiae, and C. orthopsilosis, which were multidrug-resistant. This study highlighted the need for the prompt and timely identification of clinical yeast isolates given the emergence of many rare species and their capability of causing life-threatening infections and outbreaks. In the laboratories where molecular diagnostic methods are not available, alternative services of reference laboratories can be utilized as cost-effective measures. With regard to the growing prevalence of antifungal drug resistance, antifungal susceptibility testing should be made mandatory for effective patient management.

Dataset Information

Antifungal susceptibility pattern and biofilm-related genes expression in planktonic and biofilm cells of Candida parapsilosis species complex.

Publications

Antifungal susceptibility pattern and biofilm-related genes expression in planktonic and biofilm cells of <i>Candida parapsilosis</i> species complex.

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