Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a super-resistant bacterium with strong pathogenicity, causing broad range of infections in various tissues. α-Hemolysin (Hla) is the main virulence factor of S. aureus. Brazilin (BN), is a homoisoflavonoid derivative, obtained from the wood of Caesalpinia echinata Lam (Brazil-wood), Caesalpinia sappan L (Leguminosae), and Caesalpinia violacea Standl, has been proven to exert excellent antibacterial and anti-virulence effects against S. aureus. However, the underlying mechanisms remain still unclear.
Objective: This study aims to evaluate the inhibitory effect of BN on MRSA virulence and pathogenicity and elucidate its underlying mechanisms.
Methods: Rabbit erythrocytes were used to evaluate the effect of BN on hemocytolysis. The potential target of BN was screened by transcriptomic sequencing and verified by qRT-PCR, western blot (WB), and molecular interaction experiments. The effects of BN on MRSA toxicity and pathogenicity were both validated using A549 cell and mouse skin abscess model caused by MRSA.
Results: BN attenuated the hemolytic activity of MRSA by inhibiting Hla secretion. It was also found that BN blocks its binding to the P1 promoter of the sae operon, and then reduced its transcript level. Remarkably, ΔsaeR strain exhibits significantly reduced hemolytic activity due to impaired regulation of Hla and no extra inhibitory effect was observed in the samples treated with BN. Moreover, BN relieved A549 cell damage and mouse skin abscess induced by MRSA by inhibiting SaeR.
Conclusion: These findings reveal, for the first time, BN can alleviate MRSA virulence and pathogenicity by decreasing the secretion of the Hla via inhibiting SaeR. Overall, this study suggests that BN could be a candidate for being submitted to further studies with the aim of its development as a new antibiotic against MRSA.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.phymed.2025.156616 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Splenic red pulp macrophages eliminate the liver-resistant from the blood circulation of mice.
Sci Adv
March 2025
Center for Infectious Biology, School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China.
Invasive infections by encapsulated bacteria are the major cause of human morbidity and mortality. The liver resident macrophages, Kupffer cells, form the hepatic firewall to clear many encapsulated bacteria in the blood circulation but fail to control certain high-virulence capsule types. Here we report that the spleen is the backup immune organ to clear the liver-resistant serotypes of (pneumococcus), a leading human pathogen.
View Article and Find Full Text PDF6-methyladnosine of vRNA facilitates influenza A virus replication by promoting the interaction of vRNA with polymerase proteins.
Proc Natl Acad Sci U S A
March 2025
State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730000, People's Republic of China.
6-methyladnosine (mA) modification is present in both positive- and negative-strand RNA of influenza A virus (IAV) and affects the replication and pathogenicity of IAV. However, little is known about the regulatory mechanism of mA in IAV RNA. In the present study, we identified the mA methylation of the viral RNA of different IAV subtypes and confirmed that mA modification promotes the polymerase activity and replication of IAV.
View Article and Find Full Text PDFProteasomal processing of the viral replicase ORF1 facilitates HEV-induced liver fibrosis.
Proc Natl Acad Sci U S A
March 2025
Department of Hepatobiliary and Pancreatic Surgery and Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
Chronic infections with hepatitis E virus (HEV), especially those of genotype 3 (G3), frequently lead to liver fibrosis and cirrhosis in patients. However, the causation and mechanism of liver fibrosis triggered by chronic HEV infection remain poorly understood. Here, we found that the viral multiple-domain replicase (ORF1) undergoes unique ubiquitin-proteasomal processing leading to formation of the EV-erived MAD ctivator (HDSA), a viral polypeptide lacking putative helicase and RNA polymerase domains.
View Article and Find Full Text PDFCombatting antibiotic resistance in Gardnerella vaginalis: A comparative in silico investigation for drug target identification.
PLoS One
March 2025
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
Gardnerella vaginalis is the most frequently identified bacterium in approximately 95% of bacterial vaginosis (BV) cases. This species often exhibits resistance to multiple antibiotics, posing challenges for treatment. Therefore, there is an urgent need to develop and explore alternative therapeutic strategies for managing bacterial vaginosis.
View Article and Find Full Text PDFVirulence profile of pathogenic yeasts from snakes: Alternative ways for antifungal strategies.
PLoS One
March 2025
Department of Veterinary Medicine, University of Bari Aldo Moro, Valenzano, Bari, Italy.
Reptiles may act as reservoirs or spreaders of potential pathogenic microorganisms including Candida yeasts. While the epidemiology of yeast species has been thoroughly studied, the virulence profile of isolated species is not well investigated. Therefore, this study aimed to assess the haemolytic, phospholipase, lipase activities and biofilm formation of yeasts isolated from the cloacal swabs of venomous snakes from Marrakech, Morocco (Group I, n = 40) and from non-venomous snakes from Cocullo, Italy (Group II, n = 32).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!