Silencing of Salmonella typhimurium Pathogenesis: Atenolol Acquires Efficient Anti-Virulence Activities

Abstract

The targeting of bacterial virulence is proposed as a promising approach to overcoming the bacterial resistance development to antibiotics. <i>Salmonella enterica</i> is one of the most important gut pathogens that cause a wide diversity of local and systemic illnesses. The <i>Salmonella</i> virulence is controlled by interplayed systems namely Quorum sensing (QS) and type three secretion system (T3SS). Furthermore, the <i>Salmonella</i> 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 <i>S. enterica</i> serovar Typhimurium in vitro, in silico, and in vivo. The present findings revealed a significant atenolol ability to diminish the <i>S. typhimurium</i> 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 <i>sdiA</i>, and norepinephrine membranal sensors qseC and qseE. Moreover, atenolol significantly protected mice against <i>S. typhimurium</i>. 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 <i>S. typhimurium</i> targets. In conclusion, atenolol is a promising anti-virulence candidate to alleviate the <i>S. typhimurium</i> pathogenesis by targeting its QS and T3SS systems besides diminishing the eavesdropping on the host cells.