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Typhimurium) has rapidly emerged and increased worldwide. This upsurge is especially true for the European clone of the ST34 <jats:italic>S<\/jats:italic>. Typhimurium monophasic variant. The key distinction between ST34 <jats:italic>S<\/jats:italic>. Typhimurium and its monophasic variant is that the genes that encode for second-phase flagellin (FljB) and the regions around it have been replaced with various multidrug resistance cassettes. To determine if the loss of <jats:italic>fljB<\/jats:italic> or the retention of <jats:italic>fliC<\/jats:italic>,-the gene coding for first-phase flagellin (FliC)-, would impact its pathogenicity, we constructed various mutations, including deletions of <jats:italic>fljB<\/jats:italic>, <jats:italic>fliC<\/jats:italic>, <jats:italic>fliC<\/jats:italic>\/<jats:italic>fljB<\/jats:italic>, and strains where <jats:italic>fliC<\/jats:italic> was replaced with <jats:italic>fljB<\/jats:italic>. Our results showed that the loss of <jats:italic>fljB<\/jats:italic> in ST34 <jats:italic>S<\/jats:italic>. Typhimurium and its monophasic variant does not affect bacterial motility, cell infection ability, survival in macrophages, induced pro-inflammatory cytokines secretion, virulence, or persistent infection in mice. However, the deletion of <jats:italic>fliC<\/jats:italic> caused a significant decrease in these outcomes for both strains, while the replacement of <jats:italic>fliC<\/jats:italic> with <jats:italic>fljB<\/jats:italic> only partially restored these capabilities. Consequently, we determined that FliC is predominant in the flagellar expression of ST34 <jats:italic>S<\/jats:italic>. Typhimurium other than FljB. This finding demonstrates that replacing the <jats:italic>fljB<\/jats:italic> gene with various resistance regions in ST34 <jats:italic>S.<\/jats:italic> Typhimurium monophasic variants can enhance bacterial survival under specific antibiotic farming practices and spread globally.<\/jats:p>","DOI":"10.1186\/s13567-024-01427-2","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T11:05:36Z","timestamp":1734519936000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The predominant role of FliC contributes to the flagella-related pathogenicity of ST34 S. 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