Physiological and transcriptome analysis of Candida albicans in response to X33 antimicrobial oligopeptide treatment

Qunlin Lu; Yuanxiu Wang; Xing Liao; Fu Zhou; Bin Zhang; Xiaoyu Wu

doi:10.3389/fcimb.2023.1123393

Physiological and transcriptome analysis of Candida albicans in response to X33 antimicrobial oligopeptide treatment

Front Cell Infect Microbiol. 2023 Jan 19:13:1123393. doi: 10.3389/fcimb.2023.1123393. eCollection 2023.

Authors

Qunlin Lu^{1

2

3}, Yuanxiu Wang^{1

2

3}, Xing Liao^{1

2

3}, Fu Zhou^{1

2

3}, Bin Zhang^{1

2

3}, Xiaoyu Wu^{1

2

3}

Affiliations

¹ College of Bioscience and Bioengineering, Jiangxi Agriculture University, Nanchang, China.
² Jiangxi Engineering Laboratory for the Development and Utilization of Agricultural Microbial Resources, Jiangxi Agriculture University, Nanchang, China.
³ Collaborative Innovation Center of Postharvest Key Technology and Quality Safety of Fruits and Vegetables in Jiangxi Province, Jiangxi Agriculture University, Nanchang, China.

Abstract

Introduction: Candida albicans is an opportunistic pathogenic fungus, which frequently causes systemic or local fungal infections in humans. The evolution of its drug-resistant mutants necessitate an urgent development of novel antimicrobial agents.

Results: Here, we explored the antimicrobial activity and inhibitory mechanisms of X33 antimicrobial oligopeptide (X33 AMOP) against C. albicans. The oxford cup test results showed that X33 AMOP had strong inhibitory activity against C. albicans, and its MIC and MFC were 0.625 g/L and 2.5 g/L, respectively. Moreover, SEM and TEM showed that X33 AMOP disrupted the integrity of cell membrane. The AKP, ROS, H₂O₂ and MDA contents increased, while the reducing sugar, soluble protein, and pyruvate contents decreased after the X33 AMOP treatment. This indicated that X33 AMOP could damage the mitochondrial integrity of the cells, thereby disrupting the energy metabolism by inducing oxidative stress in C. albicans. Furthermore, transcriptome analysis showed that X33 AMOP treatment resulted in the differential expression of 1140 genes, among which 532 were up-regulated, and 608 were down-regulated. These DEGs were related to protein, nucleic acid, and carbohydrate metabolism, and their expression changes were consistent with the changes in physiological characteristics. Moreover, we found that X33 AMOP could effectively inhibit the virulence attributes of C. albicans by reducing phospholipase activity and disrupting hypha formation.

Discussion: These findings provide the first-ever detailed reference for the inhibitory mechanisms of X33 AMOP against C. albicans and suggest that X33 AMOP is a potential drug candidate for treating C. albicans infections.

Keywords: Candida albicans; X33 antimicrobial oligopeptide; antimicrobial mechanism; cell damage; transcriptomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Infective Agents* / pharmacology
Antifungal Agents / pharmacology
Candida albicans*
Gene Expression Profiling
Humans
Hydrogen Peroxide / metabolism
Hydrogen Peroxide / pharmacology
Oligopeptides / genetics

Substances

Hydrogen Peroxide
Antifungal Agents
Anti-Infective Agents
Oligopeptides

Grants and funding

This study was supported by grants from the Department of Science Technology of Jiangxi Province (Grant No. 20171ACF60006), and the Collaborative Innovation Center of Postharvest Key Technology and Quality Safety of Fruits and Vegetables in Jiangxi Province.