Unsuccessful vaccination against Salmonella due to a large number of serovars, and antibiotic resistance, necessitates the development of novel therapeutics to treat salmonellosis. The development of anti-virulence agents against multi-drug-resistant bacteria is a novel strategy because of its non-bacterial feature. Hence, a thorough study of the type three secretion system (T3SS) of Salmonella would help us better understand its role in bacterial pathogenesis and development of anti-virulence agents. However, T3SS can be inhibited by different chemicals at different stages of infection and sequenced delivery of effectors can be blocked to restrict the progression of disease. This review highlights the role of T3SS-1 in the internalization, survival, and replication of Salmonella within the intestinal epithelium and T3SS inhibitors. We concluded that the better we understand the structures and functions of T3SS, the more we have chances to develop anti-virulence agents. Furthermore, greater insights into the T3SS inhibitors of Salmonella would help in the mitigation of the antibiotic resistance problem and would lead us to the era of new therapeutics against salmonellosis.
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