Fittipaldi Nahuel, Sekizaki Tsutomu, Takamatsu Daisuke, de la Cruz Domínguez-Punaro María, Harel Josée, Bui Nhat Khai, Vollmer Waldemar, Gottschalk Marcelo
Centre de Recherche en Infectiologie Porcine, Faculté de Médecine Vétérinaire, Université de Montréal, St-Hyacinthe, Canada.
Mol Microbiol. 2008 Dec;70(5):1120-35. doi: 10.1111/j.1365-2958.2008.06463.x.
Streptococcus suis is a major swine pathogen and emerging zoonotic agent. In this study we have determined the muropeptide composition of S. suis peptidoglycan (PG) and found, among other modifications, N-deacetylated compounds. Comparison with an isogenic mutant showed that the product of the pgdA gene is responsible for this specific modification which occurred in very low amounts. Low level of PG N-deacetylation correlated with absence of significant lysozyme resistance when wild-type S. suis was grown in vitro. On the other hand, expression of the pgdA gene was increased upon interaction of the bacterium with neutrophils in vitro as well as in vivo in experimentally inoculated mice, suggesting that S. suis may enhance PG N-deacetylation under these conditions. Evaluation of the DeltapgdA mutant in both the CD1 murine and the porcine models of infection revealed a significant contribution of the pgdA gene to the virulence traits of S. suis. Reflecting a severe impairment in its ability to persist in blood and decreased ability to escape immune clearance mechanisms mediated by neutrophils, the DeltapgdA mutant was highly attenuated in both models. The results of this study suggest that modification of PG by N-deacetylation is an important factor in S. suis virulence.
猪链球菌是一种主要的猪病原体和新出现的人畜共患病原体。在本研究中,我们确定了猪链球菌肽聚糖(PG)的胞壁肽组成,并发现了除其他修饰外的N-脱乙酰化化合物。与同基因突变体的比较表明,pgdA基因的产物负责这种以极低量发生的特定修饰。当野生型猪链球菌在体外生长时,PG N-脱乙酰化水平低与缺乏显著的溶菌酶抗性相关。另一方面,在体外以及在实验接种小鼠的体内,当细菌与中性粒细胞相互作用时,pgdA基因的表达增加,这表明猪链球菌在这些条件下可能增强PG N-脱乙酰化。在CD1小鼠和猪感染模型中对ΔpgdA突变体的评估揭示了pgdA基因对猪链球菌毒力特性的重要贡献。ΔpgdA突变体在两种模型中均高度减毒,这反映出其在血液中持续存在的能力严重受损以及逃避中性粒细胞介导的免疫清除机制的能力下降。本研究结果表明,通过N-脱乙酰化对PG进行修饰是猪链球菌毒力的一个重要因素。