Study on the inhibitory effect of selective estrogen receptor modulators on Streptococcus mutans

doi:10.7518/hxkq.2022.02.014

Abstract

Abstract: Objective

To screen small-molecule antibacterial drugs and investigate the antibacterial effect and mechanism of selective estrogen receptor modulators (SERMs) against Streptococcus mutans (S.mutans).

Methods

The minimum inhibitory concentration of 426 Food and Drug Administration (FDA)-approved small-molecule drugs against S. mutans was determined using the microdilution method, and the target of SERMs acting on S. mutans was explored by employing a random transposon mutant library.

Results

Among the 426 FDA-approved SERMs, toremiphene, tamoxifen, clomiphene, and raloxifene exhibited excellent antibacterial effects against S.mutans. Results of mutant library screening showed that the two mutant strains were resistant to clomiphene. The gene sequence of the resistant strains showed that the transposon insertion sites were located in the genes of smu_546 and smu_874.

Conclusion

SERMs, such as toremifene, tamoxifen, clomiphene, and raloxifene, exerted obvious antibacterial effects on S. mutans, and their targets may be proteins expressed by smu_546 and smu_874 gene.

Key words: Streptococcus mutans, dental caries, antibacterial effect, transposon mutant library

CLC Number:

Q 786

Liao Shengnan, Weitong Lü, Tang Quan, Ma Yuwen, Liu Lijia, Wang Liang, Peng Xian. Study on the inhibitory effect of selective estrogen receptor modulators on Streptococcus mutans[J]. West China Journal of Stomatology, 2022, 40(2): 218-224.

Figures/Tables 5

Tab 1

Fig 1

Fig 2

Tab 2

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类别	药物	MIC/（μmol·L^-1）
抗菌剂	201#硝唑尼特	12.5
	293#辛伐他汀	25
	338#硝酸咪康唑	6.25
激素	242#环戊丙酸睾丸素	3.125
	597#丙酸睾酮	50
选择性雌激素受体调节剂	287#枸橼酸托瑞米芬	6.25
	342#枸橼酸他莫西芬	6.25
	449#盐酸雷洛昔芬	6.25
	599#枸橼酸克罗米芬	3.125
受体激动剂/阻滞剂	395#硫酸沙丁胺醇	6.25
	486#甲磺酸多沙唑嗪	50
	500#氯雷他定	6.25
	549#盐酸奈必洛尔	25
断裂点簇集区-艾贝尔逊白血病病毒抑制剂	406#尼洛替尼	6.25
哺乳动物雷帕霉素靶蛋白抑制剂	408#雷帕霉素	6.25
	411#坦罗莫司	6.25
	424#阿瑞匹坦	6.25
	569#葡萄籽提取物	12.5

测序菌落	120 bp片段的序列	插入位点
Tn01	TATATTAACTATAGAT	Smu_20
Tn02	TATGCGGGTCCTTT	Smu_16
Tn03	TAATCATGTAGCTAAGA	Smu_766
Tn04	TAATTTCACAAGCACA	436 bp at 5side：conserved hypothetical protein；42 bp at 3side：hypothetical protein
Tn05	TACCAGCCACTAGGAA	Smu_1491
Tn06	TAATTTCACAAGCACA	436 bp at 5side：conserved hypothetical protein；42 bp at 3side：hypothetical protein
Tn07	TATGTGGCGCGGTATT	Smu_580
Tn08	TAGCAGAACTTTAAAA	*
Tn09	TATTGAAAGGATAAAT	153 bp at 5side：conserved hypothetical protein；22 bp at 3side：conserved hypothetical protein
Tn10	TAATTTCACAAGCACA	Smu_342

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