Silencing of Salmonella typhimurium Pathogenesis: Atenolol Acquires Efficient Anti-Virulence Activities.
Abrar K ThabitKhalid EljaalyAyat ZawawiTarek S IbrahimAhmed G EissaSamar S ElbaramawiWael A H HegazyMahmoud A ElfakyPublished in: Microorganisms (2022)
The targeting of bacterial virulence is proposed as a promising approach to overcoming the bacterial resistance development to antibiotics. Salmonella enterica is one of the most important gut pathogens that cause a wide diversity of local and systemic illnesses. The Salmonella virulence is controlled by interplayed systems namely Quorum sensing (QS) and type three secretion system (T3SS). Furthermore, the Salmonella spy on the host cell via sensing the adrenergic hormones enhancing its virulence. The current study explores the possible anti-virulence activities of β-adrenoreceptor blocker atenolol against S. enterica serovar Typhimurium in vitro, in silico, and in vivo. The present findings revealed a significant atenolol ability to diminish the S. typhimurium biofilm formation, invasion into HeLa cells, and intracellular replication inside macrophages. Atenolol significantly downregulated the encoding genes of the T3SS-type II, QS receptor Lux analogs sdiA , and norepinephrine membranal sensors qseC and qseE. Moreover, atenolol significantly protected mice against S. typhimurium . For testing the possible mechanisms for atenolol anti-virulence activities, an in silico molecular docking study was conducted to assess the atenolol binding ability to QS receptor SdiA and norepinephrine membranal sensors QseC. Atenolol showed the ability to compete on the S. typhimurium targets. In conclusion, atenolol is a promising anti-virulence candidate to alleviate the S. typhimurium pathogenesis by targeting its QS and T3SS systems besides diminishing the eavesdropping on the host cells.
Keyphrases
- biofilm formation
- listeria monocytogenes
- escherichia coli
- pseudomonas aeruginosa
- staphylococcus aureus
- molecular docking
- antimicrobial resistance
- candida albicans
- cystic fibrosis
- cell cycle arrest
- induced apoptosis
- molecular dynamics simulations
- single cell
- type diabetes
- gene expression
- cell therapy
- cell death
- bone marrow
- cancer therapy
- endoplasmic reticulum stress
- multidrug resistant
- drug delivery
- oxidative stress
- genome wide
- binding protein
- gram negative
- dna methylation
- angiotensin ii
- cell proliferation
- low cost
- insulin resistance
- angiotensin converting enzyme