Squalene epoxidase encoded by ERG1 affects morphogenesis and drug susceptibilities of Candida albicans
Authors: Ritu Pasrija
Tulika Prasad
Shankarling Krishnamurthy
Joachim F Ernst
Rajendra Prasad
Journal: Journal of Antimicrobial Chemotherapy (2005)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: erg1 mutant; ergosterol biosynthesis; Candida albicans; squalene epoxidase; ERG1 gene
Affiliations: School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India. 

Abstract:  Objectives: Functional characterization of the erg1 mutant of ergosterol biosynthesis of Candida albicans. Methods: We disrupted the ERG1 gene of C. albicans, which encodes squalene epoxidase (EC 1.14.99.7). Since the disruption of both alleles of ERG1 was lethal, the second allele of a heterozygous disruptant was placed under the control of a regulable promoter, MET3p, which is repressed by methionine and cysteine. Results: The reverse-phase HPLC analysis of sterol, extracted from the conditional mutant strain, showed a total lack of ergosterol and instead accumulation of squalene. This imbalance in sterol composition led to defects in growth and increased susceptibilities to drugs including fluconazole, ketoconazole, cycloheximide, nystatin, amphotericin B and terbinafine. Reduced drug efflux activity of the erg1 mutant was associated with poor surface localization of Cdr1p, suggesting that enhanced passive diffusion and reduced efflux mediated by the ABC (ATP binding cassette) transporter Cdr1p increases drug susceptibility. Additionally, conditional erg1 mutant strains were unable to form hyphae in various media. Conclusions: Taken together, our results demonstrate that the absence of ergosterol, which is one of the constituents of membrane microdomains (rafts), has a direct effect on drug susceptibility and morphogenesis of C. albicans. 

Retracted: No

PubPeer comments:
 Figure 4E. * Red boxes: two panels representing different experiments appear to show an overlap. ![file] , 
 The paper finishes with an Acknowledgement,  We acknowledge and appreciate our colleagues for their valuable efforts and comments on this paper. This invites the question: If colleagues contributed valuable efforts to the paper, why weren t they co-authors? Similar sentences appear in a number of [other problematic papers] . , 
 Fig 5D.  Protein expression of HN1 in LM3 cell lines transfected with NC, si-hsa_circ_0000092, miR-338-3p mimic, or combined si-hsa_circ_0000092 and miR-338-3p inhibitor, determined by Western blot analysis . ![file] I also compiled this montage of Western Blots, sourced from various papers, each with its own PP thread. To my mind there is (as it were) a family kinship among them all, all sampling a small corner of  morphological space . Many other family members could be adduced. Clockwise from upper left: - [Wang et al (2020)] - [Gao et al (2021)] - [Chen et al (2020)] - [He et al (2021)] . ![file] In addition, WBs from [Lv et al (2020)] *[retracted]* ![] Also the WBs from [Gao, Feng Tan (2019)] *[retracted]*. ![] This may be my over-active imagination, but the present WB seems to fit into the same genre. Is it possible for the authors to upload or link to a higher-resolution scan of the original blot , to dispel any concerns? ,