scholarly journals Cell Wall Proteome Profiling of a Candida albicans Fluconazole-Resistant Strain from a Lebanese Hospital Patient Using Tandem Mass Spectrometry—A Pilot Study

2021 ◽  
Vol 9 (6) ◽  
pp. 1161
Author(s):  
Andy Awad ◽  
Pamela El Khoury ◽  
Geovanni Geukgeuzian ◽  
Roy A. Khalaf

Candida albicans is an opportunistic pathogenic fungus responsible for high mortality rates in immunocompromised individuals. Azole drugs such as fluconazole are the first line of therapy in fungal infection treatment. However, resistance to azole treatment is on the rise. Here, we employ a tandem mass spectrometry approach coupled with a bioinformatics approach to identify cell wall proteins present in a fluconazole-resistant hospital isolate upon drug exposure. The isolate was previously shown to have an increase in cell membrane ergosterol and cell wall chitin, alongside an increase in adhesion, but slightly attenuated in virulence. We identified 50 cell wall proteins involved in ergosterol biosynthesis such as Erg11, and Erg6, efflux pumps such as Mdr1 and Cdr1, adhesion proteins such as Als1, and Pga60, chitin deposition such as Cht4, and Crh11, and virulence related genes including Sap5 and Lip9. Candidial proteins identified in this study go a long way in explaining the observed phenotypes. Our pilot study opens the way for a future large-scale analysis to identify novel proteins involved in drug-resistance mechanisms.

2016 ◽  
Vol 23 (3) ◽  
pp. 124-129 ◽  
Author(s):  
Fayza A Hassan ◽  
Fatma El-Mougy ◽  
Sahar A Sharaf ◽  
Iman Mandour ◽  
Marian F Morgan ◽  
...  

1994 ◽  
Vol 40 (4) ◽  
pp. 266-272 ◽  
Author(s):  
Kevin C. Hazen ◽  
Pati M. Glee

Cell surface hydrophobicity influences adhesion and virulence of the opportunistic fungal pathogen Candida albicans. Previous studies have shown that cell surface hydrophobicity is due to specific proteins that are exposed on hydrophobic cells but are masked by long fibrils on hydrophilic cells. This observation suggests that hydrophobic cell wall proteins may contain little or no mannosylation. In the present study, the glycosylation levels of three hydrophobic cell wall proteins (molecular mass range between 36 and 40 kDa) derived from yeast cells were examined. One hydrophilic protein (90 kDa) was also tested. Various endoglycosidases (endoglycosidase F – N-glycosidase F, O-glycosidase, β-mannosidase, N-glycosidase F), an exoglycosidase (α-mannosidase), and trifluoromethane sulfonic acid were used to deglycosylate the proteins. All four proteins were reactive to the lectin concanavalin A, demonstrating that they were mannoproteins. However, gel electrophoresis of the control and treated proteins revealed that mannosyl groups of hydrophobic proteins were less than 2 kDa in size, while the mannosyl group of the hydrophilic protein had a molecular mass of approximately 20 kDa. These results suggest that unlike many hydrophilic proteins, hydrophobic proteins may have low levels of glycosylation. Changes in glycosylation may determine exposure of hydrophobic protein regions at the cell surface.Key words: Candida albicans, cell wall, mannoproteins, hydrophobicity, fibrils.


2016 ◽  
Vol 40 (1) ◽  
pp. 151-158 ◽  
Author(s):  
Francyne Kubaski ◽  
Robert W. Mason ◽  
Akiko Nakatomi ◽  
Haruo Shintaku ◽  
Li Xie ◽  
...  

2020 ◽  
Vol 6 (4) ◽  
pp. 81
Author(s):  
Patricia L. Hall ◽  
Hong Li ◽  
Arthur F. Hagar ◽  
S. Caleb Jerris ◽  
Angela Wittenauer ◽  
...  

We screened 51,081 newborns for X-linked adrenoleukodystrophy (ALD) using a two-tiered strategy quantifying very long chain lysophosphatadylcholines (LPC). Our testing strategy used flow injection tandem mass spectrometry for the first-tier analysis of LPCs, and second-tier quantification of C26:0 LPC using liquid chromatography tandem mass spectrometry. There were 364 specimens considered abnormal using our first-tier algorithm that relied on the four LPC measurements and post-analytical tools. Second-tier test results were reported as normal or abnormal based on a cutoff for the single analyte, C26:0 LPC. Eleven cases were reported as abnormal based on second-tier test results. One male with ALD was identified, and two females with peroxisomal biogenesis disorders were also identified. A single female case remains unresolved, due to a loss to follow up after a negative molecular test result for ABCD1 gene sequencing. The positive predictive value for confirmed, clinically relevant disorders during this pilot study was 27.3%. Challenges identified during the study period were based around coverage for confirmatory testing, particularly if family members needed molecular testing, which is an ongoing issue with newborn screening in Georgia. We also encountered issues with the follow up for a patient who remained asymptomatic. Due to the different timelines involved with clinical findings in ALD, follow-up coordination may be more difficult, particularly if the child identified by newborn screening (NBS) is the only member of the family affected, or able to be tested.


2016 ◽  
Vol 118 (4) ◽  
pp. 304-309 ◽  
Author(s):  
Susan Elliott ◽  
Norman Buroker ◽  
Jason J. Cournoyer ◽  
Anna M. Potier ◽  
Joseph D. Trometer ◽  
...  

2010 ◽  
Vol 153 (3) ◽  
pp. 915-924 ◽  
Author(s):  
Ana P. Alonso ◽  
Rebecca J. Piasecki ◽  
Yan Wang ◽  
Russell W. LaClair ◽  
Yair Shachar-Hill

2011 ◽  
Vol 78 (8) ◽  
pp. 953-960 ◽  
Author(s):  
Inderneel Sahai ◽  
Thomas Zytkowicz ◽  
Srimannarayna Rao Kotthuri ◽  
Anantha Lakshmi Kotthuri ◽  
Roger B. Eaton ◽  
...  

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