Abstract

Biofilm formation plays a critical role in antimicrobial resistance in Staphylococcus aureus. Here, we investigated the potential of crude extracts of 79 Micronesian marine microorganisms to inhibit S. aureus biofilm formation. An extract of Streptomyces sp. MC025 inhibited S. aureus biofilm formation. Bioactivity-guided isolation led to the isolation of a series of 2,2′-bipyridines: collismycin B (1), collismycin C (2), SF2738 D (3), SF2738 F (4), pyrisulfoxin A (5), and pyrisulfoxin B (6). Among these bipyridines, collismycin C (2) was found to be the most effective inhibitor of biofilm formation by methicillin-sensitive S. aureus and methicillin-resistant S. aureus (MRSA), and this compound inhibited MRSA biofilm formation by more than 90% at a concentration of 50 μg/mL. The antibiofilm activity of collismycin C was speculated to be related to iron acquisition and the presence and position of the hydroxyl group of 2,2′-bipyridines.

Highlights

  • The emerging rate of antibiotic resistance is a huge threat to public health [1]

  • It is necessary to discover a new drug that can control the infection of S. aureus and methicillin-resistant S. aureus (MRSA)

  • Inhibition of biofilm formation of S. aureus is thought as a strategy to control infection of S. aureus without an additional increase in antibiotic resistance

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Summary

Introduction

Staphylococcus aureus is a major pathogen that frequently causes infections to the patients in the hospital and is well-known with high rate of antibiotic resistance such as methicillin-resistant S. aureus (MRSA) [2]. Subinhibitory concentrations of several antibiotics often increase biofilm formation [5,6,7]. Inhibition of biofilm formation of S. aureus is thought as a strategy to control infection of S. aureus without an additional increase in antibiotic resistance. The antibiofilm activities of the extracts of 79 cultured bacterial strains isolated from Micronesian marine organisms were evaluated, and a series of bipyridine compounds were. The antibiofilm activities of the isolated compounds were evaluated by biofilm formation assays in 96-well microtiter plates, and confocal microscopy, in order to identify biofilm inhibitors targeting S. aureus strains including methicillin-resistant S. aureus (MRSA). The antibiofilm mechanism of most active compound was studied

Results and Discussion
13 Ctypical
Isolation of Microbial Strains from Micronesian Marine Samples
Small-Scale Fermentation and Extraction
Biofilm-Forming Bacterial Strains and Culture Conditions
Antibiofilm Assays
Confocal Laser Microscopy

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