ObjectiveTo investigate the effect ofCandida albicans(C. albicans) on proliferation and virulence ofStreptococcus mutans(S. mutans), and to verify the role of the ergosterol pathway in it.MethodsAfter single- and co-cultivation ofC. albicanswild-type 5314 andS. mutansUA159, the absorbance value of OD600and colony-forming units (CFU) were detected to reflect the influence ofC. albicanson the growth ofS. mutans. To reflect the influence ofC. albicanson the virulence ofS. mutans, the production of extracellular polysaccharides was detected by anthrone-vitriol method, and the acid production capacity was detected by a pH meter. After single- and co-cultivation ofC. albicansmutant strains andS. mutans, the growth ofS. mutanswas evaluated by CFU. After inhibiting the ergosterol pathway by 0 mg/L, 0.012 5 mg/L, and 0.025 mg/L fluconazole for 24 h, the CFU of single- and co-cultivatedC. albicanswild-type andS. mutanswere detected.ResultsThe OD600absorbance value and CFU in theco-cultivation ofC.albicanswild-type andS. mutanswas higher than that in the single culture (P<0 .05), and the production of extracellular polysaccharides inS. mutanswas increased whenS. mutanswas co-cultured withC.albicans(P<0 .05), accompanied with a more obvious decrease of ph (P<0 .05). fourteen strains in whole 42C. albicansmutant strains lost the growth-promoting effect onS. mutans, including 6 ergosterol synthesis-related mutant strains. After co-cultivation of the 6 ergosterol synthesis-related mutant strains andS. mutans, the CFU ofS. mutansremained unchanged or decreased. After inhibiting the ergosterol pathway by 0.012 5 mg/L and 0.025 mg/L fluconazole, the CFU ofS. mutansin the co-cultivation ofC.albicanswild-type andS. mutanswas lower than that without fluconazole treatment (P<0 .05), while the cfu ofC. albicansandS. mutanssingle-cultivations did not change significantly (P>0.05) and the CFU ofC. albicansin the co-cultivation ofC. albicanswild-type andS. mutansdid not change significantly (P>0.05).ConclusionC.albicanscan enhance the growth ability and virulence ofS. mutansthrough the ergosterol-related pathway. This process can be inhibited by fluconazole, which is expected to become a novel strategy to prevent and treat dental caries.