The Antimicrobial Peptide MAF-1A Acts on the Transcriptional Response of Candida parapsilosis

2019 ◽  
Author(s):  
Rong Cheng ◽  
Wei Li ◽  
Klarke M. Sample ◽  
Qiang Xu ◽  
Lin Liu ◽  
...  

Abstract Background Candida parapsilosis is a major fungal pathogen that can cause sepsis in man. Novel antifungal agents are urgently required due to the threat of resistance to current therapeutic strategies. MAF-1A is a novel cationic antimicrobial peptide isolated from Musca domestica and is effective against a variety of Candida species. However, its antifungal mechanism is still unclear. Here, RNA-seq was used to identify differentially expressed genes (DEGs) in Candida parapsilosis after MAF-1A exposure. And then, we want to understand how the antimicrobial peptide MAF-1A work as an antifungal agent. Results The early (6 hour) response included 1122 genes with increased expression and 1065 genes with decreased expression. The late (18 hour) response was associated with the increased expression of 101 genes and decreased expression of 151 genes. When treated with MAF-1A from six to 18 hours, 42 genes were no longer expressed at elevated levels, and 25 genes that had a decreased expression pattern were reversed and demonstrated an increased expression pattern. KEGG enrichment showed that the DEGs caused by MAF-1A mainly involved amino acid synthesis and metabolism, oxidative phosphorylation, sterol synthesis and apoptosis. Conclusion These results indicate that MAF-1A may have multiple downstream effects in Candida parapsilosis. MAF-1A may exert antifungal activity by interfering with Candida parapsilosis cell membrane integrity and the function of certain organelles.

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9767
Author(s):  
Rong Cheng ◽  
Wei Li ◽  
Klarke M. Sample ◽  
Qiang Xu ◽  
Lin Liu ◽  
...  

Candida parapsilosis is a major fungal pathogen that leads to sepsis. New and more effective antifungal agents are required due to the emergence of resistant fungal strains. MAF-1A is a cationic antifungal peptide isolated from Musca domestica that is effective against a variety of Candida species. However, the mechanism(s) of its antifungal activity remains undefined. Here, we used RNA-seq to identify differentially expressed genes (DEGs) in Candida parapsilosis following MAF-1A exposure. The early (6 h) response included 1,122 upregulated and 1,065 downregulated genes. Late (18 h) responses were associated with the increased expression of 101 genes and the decreased expression of 151 genes. Upon MAF-1A treatment for 18 h, 42 genes were upregulated and 25 genes were downregulated. KEGG enrichment showed that the DEGs in response to MAF-1A were mainly involved in amino acid synthesis and metabolism, oxidative phosphorylation, sterol synthesis, and apoptosis. These results indicate that MAF-1A exerts antifungal activity through interference with Candida parapsilosis cell membrane integrity and organelle function. This provides new insight into the interaction between Candida parapsilosis and this antimicrobial peptide and serves as a reference for future Candida parapsilosis therapies.


2015 ◽  
Vol 470 (2) ◽  
pp. 243-253 ◽  
Author(s):  
Myung-Chul Chung ◽  
Scott N. Dean ◽  
Monique L. van Hoek

In addition to membrane disruption, the cathelicidin antimicrobial peptide LL-37 translocates through the bacterial inner membrane to target intracellular molecules. Our data suggest that the CAMP LL-37 is able can specifically bind to the cytoplasmic protein AcpP resulting in the inhibition of fatty acid synthesis and bacterial killing. Our studies introduce a novel mechanism for cationic antimicrobial peptides, which may be useful in future drug development for the treatment of antibiotic-resistant bacterial infection.


2020 ◽  
Vol Volume 13 ◽  
pp. 2509-2520
Author(s):  
Huiling Ma ◽  
Xinyu Zhao ◽  
Longbing Yang ◽  
Peipei Su ◽  
Ping Fu ◽  
...  

2020 ◽  
Vol 85 ◽  
pp. 47-58
Author(s):  
Y Jiang ◽  
Y Liu

Various studies have observed that increased nutrient supply promotes the growth of bloom-forming cyanobacteria, but only a limited number of studies have investigated the influence of increased nutrient supply on bloom-forming cyanobacteria at the proteomic level. We investigated the cellular and proteomic responses of Microcystis aeruginosa to elevated nitrogen and phosphorus supply. Increased supply of both nutrients significantly promoted the growth of M. aeruginosa and the synthesis of chlorophyll a, protein, and microcystins. The release of microcystins and the synthesis of polysaccharides negatively correlated with the growth of M. aeruginosa under high nutrient levels. Overexpressed proteins related to photosynthesis, and amino acid synthesis, were responsible for the stimulatory effects of increased nutrient supply in M. aeruginosa. Increased nitrogen supply directly promoted cyanobacterial growth by inducing the overexpression of the cell division regulatory protein FtsZ. NtcA, that regulates gene transcription related to both nitrogen assimilation and microcystin synthesis, was overexpressed under the high nitrogen condition, which consequently induced overexpression of 2 microcystin synthetases (McyC and McyF) and promoted microcystin synthesis. Elevated nitrogen supply induced the overexpression of proteins involved in gas vesicle organization (GvpC and GvpW), which may increase the buoyancy of M. aeruginosa. Increased phosphorus level indirectly affected growth and the synthesis of cellular substances in M. aeruginosa through the mediation of differentially expressed proteins related to carbon and phosphorus metabolism. This study provides a comprehensive description of changes in the proteome of M. aeruginosa in response to an increased supply of 2 key nutrients.


2019 ◽  
Vol 23 (19) ◽  
pp. 2102-2121
Author(s):  
Hiroyuki Kawafuchi ◽  
Lijian Ma ◽  
Md Imran Hossain ◽  
Tsutomu Inokuchi

O-Acylated 2,2,6,6-tetramethylpiperidine-N-oxyls (abbr. O-AcylTEMPOs) are easily available and stable carboxylic derivatives, but their utility in organic synthesis is unexplored in contrast to analogues, such as the N-methoxy-N-methylamides, known as Weinreb amides. Especially, the O–N unit of the O-acylTEMPOs dictates a fairly electronwithdrawing character for the carbonyl function. This enhances the reactivity and stability of the resulting enolate ions. Accordingly, O-acylTEMPOs allow various transformations and this review encompasses seven topics: (1) Reactivity of O-acylTEMPOs towards nucleophiles and chemoselective transformations, (2) Reactivity of anionic species derived from O-acylTEMPOs, (3) E-Selective Knoevenagel condensation of acetoacetylTEMPOs and synthesis of furans, (4) Electrocyclization of 2,4-dienones derived from acetoacetic derivatives and 2-substituted enals, (5) Diastereoselective addition of amide anion to O-(2-alkenoyl)TEMPOs and β-amino acid synthesis, (6) Thermolysis of O-acylTEMPOs, and (7) Applications for Umpolung reactions using O-benzoylTEMPOs, useful for the electrophilic amination of alkenes and alkynes.


2020 ◽  
Vol 13 ◽  
Author(s):  
Milad Ashrafizadeh ◽  
Saeed Samarghandian ◽  
Kiavash Hushmandi ◽  
Amirhossein Zabolian ◽  
Md Shahinozzaman ◽  
...  

Background: Ischemia/reperfusion (I/R) injury is a serious pathologic event that occurs due to restriction in blood supply to an organ, followed by hypoxia. This condition leads to enhanced levels of pro-inflammatory cytokines such as IL-6 and TNF-, and stimulation of oxidative stress via enhancing reactive oxygen species (ROS) levels. Upon reperfusion, blood supply increases, but it deteriorates condition, and leads to generation of ROS, cell membrane disruption and finally, cell death. Plant derived-natural compounds are well-known due to their excellent antioxidant and anti-inflammatory activities. Quercetin is a flavonoid exclusively found in different vegetables, herbs, and fruits. This naturally occurring compound possesses different pharmacological activities making it appropriate option in disease therapy. Quercetin can also demonstrate therapeutic effects via affecting molecular pathways such as NF-B, PI3K/Akt and so on. Methods: In the present review, we demonstrate that quercetin administration is beneficial in ameliorating I/R injury via reducing ROS levels, inhibition of inflammation, and affecting molecular pathways such as TLR4/NF-B, MAPK and so on. Results and conclusion: Quercetin can improve cell membrane integrity via decreasing lipid peroxidation. Apoptotic cell death is inhibited by quercetin via down-regulation of Bax, and caspases, and upregulation of Bcl-2. Quercetin is able to modulate autophagy (inhibition/induction) in decreasing I/R injury. Nanoparticles have been applied for delivery of quercetin, enhancing its bioavailability and efficacy in alleviation of I/R injury. Noteworthy, clinical trials have also confirmed the capability of quercetin in reducing I/R injury.


Author(s):  
Zhikai Ye ◽  
Haishuang Zhu ◽  
Shan Zhang ◽  
Jing Li ◽  
Jin Wang ◽  
...  

Designing the homogeneous assembly of the bio–nano interface to fine-tune the interactions between the nanoprobes and biological systems is of prime importance to improve the antimicrobial efficiency of nanomedicines.


Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1707
Author(s):  
Wayiza Masamba

α-Amino acids find widespread applications in various areas of life and physical sciences. Their syntheses are carried out by a multitude of protocols, of which Petasis and Strecker reactions have emerged as the most straightforward and most widely used. Both reactions are three-component reactions using the same starting materials, except the nucleophilic species. The differences and similarities between these two important reactions are highlighted in this review.


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