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C-protein α-antigen modulates the lantibiotic thusin resistance in Streptococcus agalactiae
Antonie van Leeuwenhoek ( IF 2.6 ) Pub Date : 2021-07-28 , DOI: 10.1007/s10482-021-01626-3
Nemanja Mirkovic 1, 2 , Mina Obradovic 1 , Paula M O'Connor 3, 4 , Brankica Filipic 5 , Branko Jovcic 1, 6 , Paul D Cotter 3, 4 , Milan Kojic 1
Affiliation  

Screening for producers of potent antimicrobial peptides, resulted in the isolation of Bacillus cereus BGNM1 with strong antimicrobial activity against Listeria monocytogenes. Genome sequence analysis revealed that BGNM1 contains the gene cluster associated with the production of the lantibiotic, thusin, previously identified in B. thuringiensis. Purification of the antimicrobial activity confirmed that strain BGMN1 produces thusin. Both thusin sensitive and resistant strains were detected among clinical isolates of Streptococcus agalactiae. Random mutagenesis of a thusin sensitive strain, S. agalactiae B782, was performed in an attempt to identify the receptor protein for thusin. Three independent thusin resistant mutants were selected and their complete genomes sequenced. Comparative sequence analysis of these mutants with the WT strain revealed that duplication of a region encoding a 79 amino acids repeat in a C-protein α-antigen was a common difference, suggesting it to be responsible for increased resistance to thusin. Since induced thusin resistant mutants showed higher level of resistance than the naturally resistant B761 strain, complete genome sequencing of strain B761 was performed to check the integrity of the C-protein α-antigen-encoding gene. This analysis revealed that this gene is deleted in B761, providing further evidence that this protein promotes interaction of the thusin with receptor.



中文翻译:

C-蛋白α-抗原调节无乳链球菌的羊毛硫抗生素抗性

筛选强效抗菌肽的生产者,分离出对单核细胞增生李斯特菌具有强抗菌活性的蜡状芽孢杆菌BGNM1 。基因组序列分析显示,BGNM1 包含与羊毛硫抗生素产生相关的基因簇,因此,先前在苏云金芽孢杆菌中发现。抗微生物活性的纯化证实菌株BGMN1产生如此。在无乳链球菌临床分离株中均检测到敏感菌株和耐药菌株。soin 敏感菌株的随机诱变,无乳链球菌B782 是为了鉴定 soin 的受体蛋白而进行的。选择了三个独立的 soin 抗性突变体,并对它们的完整基因组进行了测序。这些突变体与 WT 菌株的比较序列分析显示,C 蛋白 α 抗原中编码 79 个氨基酸重复序列的区域的重复是一个常见差异,表明它是增加对 soin 抗性的原因。由于诱导的抗性突变体显示出比天然抗性 B761 菌株更高的抗性水平,因此对 B761 菌株进行了完整的基因组测序以检查 C 蛋白 α-抗原编码基因的完整性。该分析表明该基因在 B761 中缺失,进一步证明该蛋白促进了 soin 与受体的相互作用。

更新日期:2021-07-28
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