Colonization Mediated by T6SS-ClpV Disrupts Host Gut Microbiota and Enhances Virulence of <i>Salmonella enterica</i> serovar Typhimurium

<i>Salmonella enterica</i> serovar Typhimurium (<i>S.</i> Typhimurium) is a common foodborne enteric pathogen that infects humans or mammals and colonizes the intestinal tract primarily by invading the host following ingestion. Meanwhile, ClpV is a core secreted protein of the bacterial type VI secretion system (T6SS). Because elucidating ClpV's role in the pathogenesis of T6SS is pivotal for revealing the virulence mechanism of <i>Salmonella</i>, in our study, <i>clpV</i> gene deletion mutants were constructed using a λ-red-based recombination system, and the effect of <i>clpV</i> mutation on SL1344's pathogenicity was examined in terms of stress resistance, motility, cytokine secretion, gut microbiota, and a BALB/c mouse model. Among the results, ClpV affected SL1344's motility and was also involved in cell invasion, adhesion, and intracellular survival in the MDBK cell model but did not affect invasion or intracellular survival in the RAW264.7 cell model. Moreover, <i>clpV</i> gene deletion significantly reduced the transcription levels of GBP2b, IFNB1, IL-6, NLRP3, NOS2, and TNF-α proinflammatory factor levels but significantly increased transcription levels of IL-4 and IL-10 anti-inflammatory factors. Last, ClpV appeared to closely relate to the pathogenicity of <i>S.</i> Typhimurium <i>in vivo</i>, which can change the gut environment and cause dysbiosis of gut microbiota. Our findings elucidate the functions of ClpV in <i>S</i>. Typhimurium and illustrating interactions between T6SS and gut microbiota help to clarify the mechanisms of the pathogenesis of foodborne diseases.