Pyrisulfoxin A

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.

Background: Inhalation of fine particulate matter (PM2.5) is associated with elevated pulmonary injury caused by the loss of vascular barrier integrity. Marine microbial natural products isolated from microbial culture broths were screened for pulmonary protective effects against PM2.5. Two 2,2'-bipyridine compounds isolated from a red alga-associated Streptomyces sp. MC025-collismycin C (2) and pyrisulfoxin A (5)-were found to inhibit PM2.5-mediated vascular barrier disruption. Purpose: To confirm the inhibitory effects of collismycin C and pyrisulfoxin A on PM2.5-induced pulmonary injury STUDY DESIGN: In this study, we investigated the beneficial effects of collismycin C and pyrisulfoxin A on PM-induced lung endothelial cell (EC) barrier disruption and pulmonary inflammation. Methods: Permeability, leukocyte migration, proinflammatory protein activation, reactive oxygen species (ROS) generation, and histology were evaluated in PM2.5-treated ECs and mice. Results: Collismycin C and pyrisulfoxin A significantly scavenged PM2.5-induced ROS and inhibited the ROS-induced activation of p38 mitogen-activated protein kinase as well as activated Akt, which helped in maintaining endothelial integrity, in purified pulmonary endothelial cells. Furthermore, collismycin C and pyrisulfoxin A reduced vascular protein leakage, leukocyte infiltration, and proinflammatory cytokine release in the bronchoalveolar lavage fluid of PM-treated mice. Conclusion: These data suggested that collismycin C and pyrisulfoxin A might exert protective effects on PM-induced inflammatory lung injury and vascular hyperpermeability.