Azalomycin F5a, a polyhydroxy macrolide binding to the polar head of phospholipid and targeting to lipoteichoic acid to kill methicillin-resistant Staphylococcus aureus

Yuan, Ganjun; Li, Xu; Xu, Xuejie; Li, Peibo; Zhong, Qiuyan; Xia, Hailin; Hu, Yue; Li, Ping‐Yi; Song, Xiaoyuan; Li, Junfang; Liu, Qianru

doi:10.1016/j.biopha.2018.11.067

Cited by 22 publications

(46 citation statements)

References 82 publications

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“…Our previous works indicate that azalomycin F 5a could bind to the polar head of cell membrane phospholipids and target lipoteichoic acids, and eventually damage the cell membrane and lead to the cell lysis or/and autolysis of S. aureus [11,37]. Therefore, we believe that azalomycin F 5a could rapidly penetrate the S. aureus biofilm to damage the cell membranes, leading to cell lysis or autolysis, similar to daptomycin being able to quickly penetrate S. epidermidis biofilms [38].…”

Section: Discussionmentioning

confidence: 93%

“…Azalomycin F 5a (purity, 98.2%) was isolated from the fermentation of Streptomyces hygroscopicus var. azalomyceticus according to our published methods [1], and widely used in our previous works [11,37,51]. The stock solution of azalomycin F 5a , stored at −20 • C, was prepared by dissolving in dimethyl sulfoxide (DMSO) to obtain a concentration of 2048 µg/mL.…”

Section: Azalomycin F 5amentioning

confidence: 99%

“…Biofilms were grown on silicone disks as described above. After treated with azalomcyin F 5a , the discs were gently washed twice with PBS to remove nonadherent cells, and then erectly placed in the wells of a 24-well plate containing PBS and nucleic acid stains SYTO-9/PI (1:5) provided in a BacLight Live/Dead staining kit (Invitrogen) [11,25,26]. After the plate stayed for 15 min at 25 • C in the dark, the disks were taken from wells, and observed under a confocal laser scanning microscope (Olympus Fluoview TM FV1000) equipped with a detector and filter sets for monitoring SYTO-9 and PI.…”

Section: Confocal Laser Scanning Microscopymentioning

confidence: 99%

“…The antimicrobial assays indicated that azalomycin F 5a , together with its derivatives, had remarkable anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activities [10]. Our recent studies have also shown that azalomycin F 5a simultaneously targets cell membrane phospholipid and lipoteichoic acid (LTA), resulting in increases in the cell membrane permeability of S. aureus [11]. LTA is an anionic surface polymer anchoring to the cell membrane of Gram-positive bacteria and consisting of glycerol phosphate repeats [12,13].…”

Section: Introductionmentioning

confidence: 99%

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Azalomycin F5a Eradicates Staphylococcus aureus Biofilm by Rapidly Penetrating and Subsequently Inducing Cell Lysis

Yuan

et al. 2020

IJMS

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Antimicrobial resistance has emerged as a serious threat to public health. Bacterial biofilm, as a natural lifestyle, is a major contributor to resistance to antimicrobials. Azalomycin F5a, a natural guanidine-containing polyhydroxy macrolide, has remarkable activities against Gram-positive bacteria, including Staphylococcus aureus, a major causative agent of hospital-acquired infections. To further evaluate its potential to be developed as a new antimicrobial agent, its influence on S. aureus biofilm formation was evaluated using the crystal violet method, and then its eradication effect against mature biofilms was determined by confocal laser scanning microscopy, the drop plate method, and regrowth experiments. The results showed that azalomycin F5a could significantly inhibit S. aureus biofilm formation, and such effects were concentration dependent. In addition, it can also eradicate S. aureus mature biofilms with the minimum biofilm eradication concentration of 32.0 μg/mL. As extracellular deoxyribonucleic acid (eDNA) plays important roles in the structural integrity of bacterial biofilm, its influence on the eDNA release in S. aureus biofilm was further analyzed using gel electrophoresis. Combined with our previous works, these results indicate that azalomycin F5a could rapidly penetrate biofilm and causes damages to the cell membrane, leading to an increase in DNase release and eventually eradicating S. aureus biofilm.

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Section: Discussionmentioning

confidence: 93%

Section: Azalomycin F 5amentioning

confidence: 99%

Section: Confocal Laser Scanning Microscopymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Azalomycin F5a Eradicates Staphylococcus aureus Biofilm by Rapidly Penetrating and Subsequently Inducing Cell Lysis

Yuan

et al. 2020

IJMS

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“…azalomyceticus revealed that the guanidyl side chain of the marginolactone antibiotic plays pivotal role in antibacterial effect. Consequently, modification of agmatinase enzyme encoding gene expression emerges as a promising target to enhance antibacterial activity (Yuan et al 2019 ). Expression profiling revealed DEGs encoding enzymes responsible for fatty acid biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

Structural and functional comparison of Saccharomonospora azurea strains in terms of primycin producing ability

Kovacs

Seffer

Pénzes-Hűvös

et al. 2020

World J Microbiol Biotechnol

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Emerging and re-emerging microbial pathogens, together with their rapid evolution and adaptation against antibiotics, highlight the importance not only of screening for new antimicrobial agents, but also for deepening knowledge about existing antibiotics. Primycin is a large 36-membered non-polyene macrolide lactone exclusively produced by Saccharomonospora azurea. This study provides information about strain dependent primycin production ability in conjunction with the structural, functional and comparative genomic examinations. Comparison of high- and low-primycin producer strains, transcriptomic analysis identified a total of 686 differentially expressed genes (DEGs), classified into diverse Cluster of Orthologous Groups. Among them, genes related to fatty acid synthesis, self-resistance, regulation of secondary metabolism and agmatinase encoding gene responsible for catalyze conversion between guanidino/amino forms of primycin were discussed. Based on in silico data mining methods, we were able to identify DEGs whose altered expression provide a good starting point for the optimization of fermentation processes, in order to perform targeted strain improvement and rational drug design.

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Synthetic and natural guanidine derivatives as antitumor and antimicrobial agents: A review

Gomes

Varela

Pires

et al. 2023

Bioorganic Chemistry

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Azalomycin F5a, a polyhydroxy macrolide binding to the polar head of phospholipid and targeting to lipoteichoic acid to kill methicillin-resistant Staphylococcus aureus

Cited by 22 publications

References 82 publications

Azalomycin F5a Eradicates Staphylococcus aureus Biofilm by Rapidly Penetrating and Subsequently Inducing Cell Lysis

Azalomycin F5a Eradicates Staphylococcus aureus Biofilm by Rapidly Penetrating and Subsequently Inducing Cell Lysis

Structural and functional comparison of Saccharomonospora azurea strains in terms of primycin producing ability

Synthetic and natural guanidine derivatives as antitumor and antimicrobial agents: A review

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