Exel Catharina E, Tamminga Sara M, Man-Bovenkerk Sandra, Temming A Robin, Hendriks Astrid, Spaninks Mirlin, van Sorge Nina M, Benedictus Lindert
Department Population Health Sciences, Division Farm Animal Health, Utrecht University, Utrecht, the Netherlands.
Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Vet Microbiol. 2025 Mar;302:110403. doi: 10.1016/j.vetmic.2025.110403. Epub 2025 Jan 20.
Staphylococcus aureus (S. aureus) is one of the major causes of bovine mastitis, a disease with detrimental effects on health and wellbeing. Current control measures are costly, laborious and not always effective in eradicating S. aureus. The cell wall-linked polysaccharide wall teichoic acid (WTA) is highly immunogenic in humans and is considered as a prospective vaccine antigen based on promising pre-clinical studies in animals. WTA consist of polymerized ribitol-phosphate backbone that is modified with N-acetylglucosamine (GlcNAc) moieties in different configurations by the glycosyltransferases TarS (β-1,4-GlcNAc), TarM (α-1,4-GlcNAc) and TarP (β-1,3-GlcNAc). This study aimed to characterize the presence and genetic variation in tarS, tarM and tarP in bovine-associated S. aureus strains and how this impacts WTA-glycoprofile. Bioinformatic analyses of a whole genome sequence database consisting of 1047 S. aureus, 10 S. schweitzeri, and 6 S. argenteus strains showed that over 99% of strains contained tarS, 34 % also contained tarM, while 5 % of the strains encoded tarP in addition to tarS. The distribution of WTA-glycosyltransferase genes was similar to what has been reported for human-associated S. aureus strains. Phenotypic analysis of WTA glycosylation by flow cytometry corroborated with tarS/tarM/tarP gene presence. The WTA glycoprofile was variable between bovine-associated strains and the levels and ratios of GlcNAcylation were affected by growth conditions. Interestingly, a divergent tarM allele was present in strains of clonal complexes (CC) 49 and the mastitis-associated CC151, but its function was similar to canonical tarM. In conclusion, we demonstrated that bovine-associated S. aureus strains show similar variation in WTA GlcNAc decoration as human S. aureus strains, despite the presence of a divergent tarM allele.
金黄色葡萄球菌是牛乳腺炎的主要病因之一,这种疾病对健康和福祉有不利影响。当前的控制措施成本高昂、费力,而且在根除金黄色葡萄球菌方面并不总是有效。细胞壁连接的多糖壁磷壁酸(WTA)在人类中具有高度免疫原性,基于在动物身上进行的有前景的临床前研究,它被认为是一种有前景的疫苗抗原。WTA由聚合的核糖醇 - 磷酸主链组成,该主链由糖基转移酶TarS(β - 1,4 - 氨基葡萄糖)、TarM(α - 1,4 - 氨基葡萄糖)和TarP(β - 1,3 - 氨基葡萄糖)以不同构型用N - 乙酰葡萄糖胺(GlcNAc)部分进行修饰。本研究旨在表征牛源金黄色葡萄球菌菌株中tarS、tarM和tarP的存在及遗传变异,以及这如何影响WTA - 糖谱。对由1047株金黄色葡萄球菌、10株施氏葡萄球菌和6株银色葡萄球菌组成的全基因组序列数据库进行生物信息学分析表明,超过99%的菌株含有tarS,34%还含有tarM,而5%的菌株除了tarS还编码tarP。WTA - 糖基转移酶基因的分布与人类相关金黄色葡萄球菌菌株的报道相似。通过流式细胞术对WTA糖基化进行的表型分析与tarS/tarM/tarP基因的存在情况相符。牛源菌株之间的WTA糖谱各不相同,并且GlcNAcylation的水平和比例受生长条件影响。有趣的是,在克隆复合体(CC)49和与乳腺炎相关的CC151的菌株中存在一个不同的tarM等位基因,但其功能与典型的tarM相似。总之,我们证明,尽管存在一个不同的tarM等位基因,但牛源金黄色葡萄球菌菌株在WTA GlcNAc修饰方面表现出与人类金黄色葡萄球菌菌株相似的变异。