Anti-virulence potential of 2-hydroxy-4-methoxybenzaldehyde against methicillin-resistant Staphylococcus aureus and its clinical isolates

Burgeoning antibiotic resistance among bacterial pathogens necessitates the alternative treatment options to control the multidrug-resistant bacterial infections. Plant secondary metabolites, a significant source of structurally diverse compounds, posses several biological activities. The present study was designed to investigate the anti-virulence potential of least explored phytocompound 2-hydroxy-4-methoxybenzaldehyde (HMB) against methicillin-resistant Staphylococcus aureus (MRSA) and its clinical isolates. The minimum inhibitory concentration of HMB was found to be 1024 μg/ml. HMB at sub-MIC (200 μg/ml) exhibited a profound staphyloxanthin inhibitory activity against MRSA and its clinical isolates. Besides, growth curve analysis revealed the non-bactericidal activity of HMB at its sub-MIC. Other virulences of MRSA such as lipase, nuclease, and hemolysin were also significantly inhibited upon HMB treatment. The observations made out of blood and H2O2 sensitivity assay suggested that HMB treatment sensitized the test pathogens and aided the functions of host immune responses. Transcriptomic analysis revealed that HMB targets the virulence regulatory genes such as sigB and saeS to attenuate the production of virulence arsenal in MRSA. Further, the result of in vitro cytotoxicity assay using PBMC cells portrayed the non-toxic nature of HMB. To our knowledge, for the first time, the present study reported the virulence inhibitory property of HMB against MRSA along with plausible molecular mechanisms. Additional studies incorporating in vivo analysis and omics technologies are required to explore the anti-virulence potential of HMB and its mode of action during MRSA infections.