Abstract
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.
Highlights
Azalomycin F5a (Figure 1), produced by marine Streptomyces sp. 211726, was a main component of the azalomycin F complex, including twelve 36-membered polyhydroxy macrolides [1,2]
Without the intervention of azalomycin F5a, the biofilm of S. aureus was formed in the wells of the 96-well plates by following our established protocols [25,26], and the number of biofilms was determined using the crystal violet method
Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to observe the structure and growth of biofilm covered on disks
Summary
Azalomycin F5a (Figure 1), produced by marine Streptomyces sp. 211726, was a main component of the azalomycin F complex, including twelve 36-membered polyhydroxy macrolides [1,2]. 211726, was a main component of the azalomycin F complex, including twelve 36-membered polyhydroxy macrolides [1,2]. It was isolated from other streptomycete strains [3,4,5], and has shown remarkable antibacterial and antifungal activities [2,3,4,5]. The antimicrobial assays indicated that azalomycin F5a, together with its derivatives, had remarkable anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activities [10]. Our recent studies have shown that azalomycin F5a simultaneously targets cell membrane phospholipid and lipoteichoic acid (LTA), resulting in increases in the cell membrane permeability of S. aureus [11]. Thereby, a review on the chemistry, bioactivity and antimicrobial structure–activity relationships of these compounds was recently presented by us [6], and the conclusion is that these compounds have great potential to be developed into antimicrobial drugs
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