1887

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Volume 73, Issue 7

The role of acetylcysteine on adhesion and biofilm formation of isolated from catheter-related candidemia Open Access

Abstract

Anti-fungal agents are increasingly becoming less effective due to the development of resistance. In addition, it is difficult to treat organisms that form biofilms due to a lack of ability of drugs to penetrate the biofilms. We are attempting to assess the effect of a new therapeutic agent, -acetylcysteine (NAC), on adhesion and biofilm formation in clinical strains. Meanwhile, to detect the transcription level changes of adhesion and biofilm formation-associated genes ( and ) when administrated with NAC in strains, furthermore, to explore the mechanism of drug interference on biofilms.

N-acetylcysteine (NAC) exhibits certain inhibitory effects on adhesion and biofilm formation in C. parapsilosis clinical strains from CRBSIs through: (1) down-regulating the expression of the CpEFG1 gene, making it a highly potential candidate for the treatment of C. parapsilosis catheter-related bloodstream infections (CRBSIs), (2) regulating the metabolism and biofilm -forming factors of cell structure.

To determine whether non-antifungal agents can exhibit inhibitory effects on adhesion, amounts of total biofilm formation and metabolic activities of isolates from candidemia patients, NAC was added to the yeast suspensions at different concentrations, respectively. Reverse transcription was used to detect the transcriptional levels of adhesion-related genes ( and ) and biofilm formation-related factors ( and ) in the knockout strain, CP7 and CP5 clinical strains in the presence of NAC. To further explore the mechanism of NAC on the biofilms of , RNA sequencing was used to calculate gene expression, comparing the differences among samples. Gene Ontology (GO) enrichment analysis helps to illustrate the difference between two particular samples on functional levels.

A high concentration of NAC reduces the total amount of biofilm formation in . Following co-incubation with NAC, the expression of in both CP7 and CP5 clinical strains decreased, while there were no significant changes in the transcriptional levels of compared with the untreated strain. GO enrichment analysis showed that the metabolism and biofilm-forming factors of cell structure were all regulated after NAC intervention.

The non-antifungal agent NAC exhibits certain inhibitory effects on clinical isolate biofilm formation by down-regulating the expression of the gene, making it a highly potential candidate for the treatment of catheter-related bloodstream infections.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): adhesion , biofilm formation , Candida parapsilosis , candidemia and N-acetylcysteine
Funding
This study was supported by the:
  • Fundamental Research Funds for Central Universities of the Central South University (Award NO.2042022kf1096)
    • Principle Award Recipient: ZuoXiaoshu
© 2024 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2024-07-03
2024-09-15
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References

  1. Quindós G. Epidemiology of candidaemia and invasive candidiasis. A changing face. Rev Iberoam Micol 2014; 31:42–48 [View Article] [PubMed]
     [Google Scholar]
  2. Zhang W, Song X, Wu H, Zheng R. Epidemiology, risk factors and outcomes of Candida albicans vs. non-albicans candidaemia in adult patients in Northeast China. Epidemiol Infect 2019; 147:e277 [View Article] [PubMed]
     [Google Scholar]
  3. Xiao Z, Wang Q, Zhu F, An Y. Epidemiology, species distribution, antifungal susceptibility and mortality risk factors of candidemia among critically ill patients: a retrospective study from 2011 to 2017 in a teaching hospital in China. Antimicrob Resist Infect Control 2019; 8:89 [View Article] [PubMed]
     [Google Scholar]
  4. Li Y, Du M, Chen L-A, Liu Y, Liang Z. Nosocomial bloodstream infection due to Candida spp. in China: species distribution, clinical features, and outcomes. Mycopathologia 2016; 181:485–495 [View Article] [PubMed]
     [Google Scholar]
  5. Yamin DH, Husin A, Harun A. Risk factors of Candida parapsilosis catheter-related bloodstream infection. Front Public Health 2021; 9:631865 [View Article] [PubMed]
     [Google Scholar]
  6. Puig-Asensio M, Padilla B, Garnacho-Montero J, Zaragoza O, Aguado JM et al. Epidemiology and predictive factors for early and late mortality in Candida bloodstream infections: a population-based surveillance in Spain. Clin Microbiol Infect 2014; 20:245–254 [View Article] [PubMed]
     [Google Scholar]
  7. Xiao M, Sun Z-Y, Kang M, Guo D-W, Liao K et al. Five-year national surveillance of invasive Candidiasis: species distribution and azole susceptibility from the China hospital invasive fungal surveillance NET (CHIF-NET) study. J Clin Microbiol 2018; 56:e00577-18 [View Article] [PubMed]
     [Google Scholar]
  8. Wang H, Xiao M, Chen SC-A, Kong F, Sun Z-Y et al. In vitro susceptibilities of yeast species to fluconazole and voriconazole as determined by the 2010 National China Hospital Invasive Fungal Surveillance NET (CHIF-NET) study. J Clin Microbiol 2012; 50:3952–3959 [View Article] [PubMed]
     [Google Scholar]
  9. Branco J, Miranda IM, Rodrigues AG. Candida parapsilosis virulence and antifungal resistance mechanisms: a comprehensive review of key determinants. J Fungi 2023; 9:80 [View Article] [PubMed]
     [Google Scholar]
  10. Tóth R, Nosek J, Mora-Montes HM, Gabaldon T, Bliss JM et al. Candida parapsilosis: from genes to the bedside. Clin Microbiol Rev 2019; 32:e00111-18 [View Article] [PubMed]
     [Google Scholar]
  11. Kuhn DM, Chandra J, Mukherjee PK, Ghannoum MA. Comparison of biofilms formed by Candida albicans and Candida parapsilosis on bioprosthetic surfaces. Infect Immun 2002; 70:878–888 [View Article] [PubMed]
     [Google Scholar]
  12. Tenório MC dos S, Graciliano NG, Moura FA, Oliveira ACM de, Goulart MOF. N-Acetylcysteine (NAC): impacts on human health. Antioxidants 2021; 10:967 [View Article] [PubMed]
     [Google Scholar]
  13. Olofsson A-C, Hermansson M, Elwing H. N-acetyl-L-cysteine affects growth, extracellular polysaccharide production, and bacterial biofilm formation on solid surfaces. Appl Environ Microbiol 2003; 69:4814–4822 [View Article] [PubMed]
     [Google Scholar]
  14. Mahmoud Abd El-Baky R, Mohamed Mohamed Abo El Ela D, Fadl Mamoud Gad G. N-Acetylcysteine inhibits and eradicates Candida albicans biofilms. Am J Infect Dis Microbiol 2014122–130 [View Article]
     [Google Scholar]
  15. Blasi F, Page C, Rossolini GM, Pallecchi L, Matera MG et al. The effect of N -acetylcysteine on biofilms: implications for the treatment of respiratory tract infections. Respirat Med 2016; 117:190–197 [View Article]
     [Google Scholar]
  16. Zuo X-S, Liu Y, Cai X, Zhan L, Hu K. Association of different Candida species with catheter-related candidemia, and the potential antifungal treatments against their adhesion properties and biofilm-forming capabilities. J Clin Lab Anal 2021; 35:e23738 [View Article] [PubMed]
     [Google Scholar]
  17. Ding C, Butler G. Development of a gene knockout system in Candida parapsilosis reveals a conserved role for BCR1 in biofilm formation. Eukaryot Cell 2007; 6:1310–1319 [View Article] [PubMed]
     [Google Scholar]
  18. Silva-Dias A, Miranda IM, Rocha R, Monteiro-Soares M, Salvador A et al. A novel flow cytometric protocol for assessment of yeast cell adhesion. Cytometry A 2012; 81:265–270 [View Article] [PubMed]
     [Google Scholar]
  19. Govender NP, Patel J, Magobo RE, Naicker S, Wadula J et al. Emergence of azole-resistant Candida parapsilosis causing bloodstream infection: results from laboratory-based sentinel surveillance in South Africa. J Antimicrob Chemother 2016; 71:1994–2004 [View Article] [PubMed]
     [Google Scholar]
  20. Zuo X-S, Liu Y, Hu K. Epidemiology and risk factors of candidemia due to Candida parapsilosis in an intensive care unit. Rev Inst Med Trop Sao Paulo 2021; 63:e20 [View Article] [PubMed]
     [Google Scholar]
  21. Nakagawa Y, Inomata A, Ogata A, Nakae D. Comparative effects of sulfhydryl compounds on target organellae, nuclei and mitochondria, of hydroxylated fullerene-induced cytotoxicity in isolated rat hepatocytes. J Appl Toxicol 2015; 35:1465–1472 [View Article] [PubMed]
     [Google Scholar]
  22. Mahmoud Abd El-Baky R, Mohamed Mohamed Abo El Ela D, Fadl Mamoud Gad G. N-Acetylcysteine inhibits and eradicates Candida albicans biofilms. Am J Infect Dis Microbiol 2014122–130 [View Article]
     [Google Scholar]
  23. Costa F, Sousa DM, Parreira P, Lamghari M, Gomes P et al. N-acetylcysteine-functionalized coating avoids bacterial adhesion and biofilm formation. Sci Rep 2017; 7:17374 [View Article] [PubMed]
     [Google Scholar]
  24. Bertini A, Zoppo M, Lombardi L, Rizzato C, De Carolis E et al. Targeted gene disruption in Candida parapsilosis demonstrates a role for CPAR2_404800 in adhesion to a biotic surface and in a murine model of ascending urinary tract infection. Virulence 2016; 7:85–97 [View Article] [PubMed]
     [Google Scholar]
  25. Neale MN, Glass KA, Longley SJ, Kim DJ, Laforce-Nesbitt SS et al. Role of the inducible adhesin CpAls7 in binding of Candida parapsilosis to the extracellular matrix under fluid shear. Infect Immun 2018; 86:e00892-17 [View Article] [PubMed]
     [Google Scholar]
  26. Holland LM, Schröder MS, Turner SA, Taff H, Andes D et al. Comparative phenotypic analysis of the major fungal pathogens Candida parapsilosis and Candida albicans. PLoS Pathog 2014; 10:e1004365 [View Article] [PubMed]
     [Google Scholar]
  27. Branco J, Martins-Cruz C, Rodrigues L, Silva RM, Araújo-Gomes N et al. The transcription factor Ndt80 is a repressor of Candida parapsilosis virulence attributes. Virulence 2021; 12:601–614 [View Article] [PubMed]
     [Google Scholar]
  28. Cillingová A, Tóth R, Mojáková A, Zeman I, Vrzoňová R et al. Transcriptome and proteome profiling reveals complex adaptations of Candida parapsilosis cells assimilating hydroxyaromatic carbon sources. PLoS Genet 2022; 18:e1009815 [View Article] [PubMed]
     [Google Scholar]
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The role of N-acetylcysteine on adhesion and biofilm formation of Candida parapsilosis isolated from catheter-related candidemia
J. Med. Microbiol. 73, 001848 (2024); https://doi.org/10.1099/jmm.0.001848
/content/journal/jmm/10.1099/jmm.0.001848
/content/journal/jmm/10.1099/jmm.0.001848
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