Effective Antibiofilm Polyketides against Staphylococcus aureus from the Pyranonaphthoquinone Biosynthetic Pathways of Streptomyces Species

Abstract

dStreptomyces bacteria are renowned for their ability to produce bioactive secondary metabolites. Recently, synthetic biology has enabled the production of intermediates and shunt products, which may have altered biological activities compared to the end products of the pathways. Here, we have evaluated the potential of recently isolated alnumycins and other closely related pyranonaphthoquinone (PNQ) polyketides against Staphylococcus aureus biofilms. The antimicrobial potency of the compounds against planktonic cells and biofilms was determined by redox dye-based viability staining, and the antibiofilm efficacy of the compounds was confirmed by viable counting. A novel antistaphylococcal polyketide, alnumycin D, was identified. Unexpectedly, the C-ribosylated pathway shunt product alnumycin D was more active against planktonic and biofilm cells than the pathway end product alnumycin A, where a ribose unit has been converted into a dioxane moiety. The evaluation of the antibiofilm potential of other alnumycins revealed that the presence of the ribose moiety in pyranose form is essential for high activity against preformed biofilms. Furthermore, the antibiofilm potential of other closely related PNQ polyketides was examined. Based on their previously reported activity against planktonic S. aureus cells, granaticin B, kalafungin, and medermycin were also selected for testing, and among them, granaticin B was found to be the most potent against preformed biofilms. The most active antibiofilm PNQs, alnumycin D and granaticin B, share several structural features that may be important for their antibiofilm activity. They are uncharged, glycosylated, and also contain a similar oxygenation pattern of the lateral naphthoquinone ring. These findings highlight the potential of antibiotic biosynthetic pathways as a source of effective antibiofilm compounds.

Antimicrobial and anti-biofilm activity of hexadentated macrocyclic complex of copper (II) derived from thiosemicarbazide against Staphylococcus aureus

“…Similarly, the anti-biofilm activity was also assessed using resazurin. The protocol used was same as mentioned above with slight modifications 29 , 30 . Briefly, the anti-biofilm effect of Cu complex was determined on 24 h and 72 h old biofilms.…”

Bioactivities and molecular networking-based elucidation of metabolites of potent actinobacterial strains isolated from the Unkeshwar geothermal springs in India

“…A few studies have demonstrated that Streptomyces species modulate biolm formation in P. aeruginosa and S. aureus cultures. 34,35 Micromonospora species have rarely been reported for their anti-biolm activities; however, our strain showed higher biolm inhibition as compared to the Streptomyces strain. We also tested the anticancer activity of the extracts using the breast cancer cell line MCF7.…”

Formation, Antibiotic Resistance, and Control Strategies of Staphylococcus epidermidis Biofilm

“…Special plants and Actinomycetes are both rich sources of bioactive substances, notably antibiotics, enzymes, enzyme inhibitors, and pharmacologically active agents [4,5]. Moreover, some Actinomycete species were reported to produce inhibitors against biofilm formation by Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa [6][7][8][9].…”