Abstract
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.