Ahmad Zuleeza, Harvey Richard M, Paton James C, Standish Alistair J, Morona Renato
Research Centre for Infectious Diseases, Department of Molecular & Cellular Biology, School of Biological Sciences, The University of Adelaide, South Australia, Australia.
PLoS One. 2018 Jan 2;13(1):e0190402. doi: 10.1371/journal.pone.0190402. eCollection 2018.
Streptococcus pneumoniae is the leading cause of community-acquired pneumonia in all ages worldwide, and with ever-increasing antibiotic resistance, the understanding of its pathogenesis and spread is as important as ever. Recently, we reported the presence of a Low Molecular Weight Tyrosine Phosphatase (LMWPTP) Spd1837 in the pneumococcus. This protein is encoded in an operon, OM001 with two other genes, with previous work implicating this operon as important for pneumococcal virulence. Thus, we set out to investigate the role of the individual genes in the operon during pneumococcal pathogenesis. As LMWPTPs play a major role in capsular polysaccharide (CPS) biosynthesis in many bacteria, we tested the effect of mutating spd1837 and its adjacent genes, spd1836 and spd1838 on CPS levels. Our results suggest that individual deletion of the genes, including the LMWPTP, did not modulate CPS levels, in multiple conditions, and in different strain backgrounds. Following in vivo studies, Spd1836 was identified as a novel virulence factor during pneumococcal invasive disease, in both the lungs and blood, with this protein alone responsible for the effects of operon's role in virulence. We also showed that a deletion in spd1836, spd1838 or the overall OM001 operon reduced survival in human saliva during the conditions that mimic transmission compared to the wildtype strain. With studies suggesting that survival in human saliva may be important for transmission, this study identifies Spd1836 and Spd1838 as transmission factors, potentially facilitating the spread of the pneumococcus from person to person. Overall, this study hopes to further our understanding of the bacterial transmission that precedes disease and outbreaks.
肺炎链球菌是全球所有年龄段社区获得性肺炎的主要病因，随着抗生素耐药性的不断增加，对其发病机制和传播的了解与以往一样重要。最近，我们报道了肺炎链球菌中存在一种低分子量酪氨酸磷酸酶（LMWPTP）Spd1837。该蛋白在一个操纵子OM001中与另外两个基因一起编码，先前的研究表明该操纵子对肺炎链球菌的毒力很重要。因此，我们着手研究该操纵子中各个基因在肺炎链球菌发病机制中的作用。由于LMWPTPs在许多细菌的荚膜多糖（CPS）生物合成中起主要作用，我们测试了突变spd1837及其相邻基因spd1836和spd1838对CPS水平的影响。我们的结果表明，在多种条件下和不同菌株背景下，单个基因（包括LMWPTP）的缺失并未调节CPS水平。在体内研究之后，Spd1836被确定为肺炎链球菌侵袭性疾病（在肺部和血液中）期间的一种新型毒力因子，仅该蛋白就导致了操纵子在毒力方面的作用。我们还表明，与野生型菌株相比，在模拟传播的条件下，spd1836、spd1838或整个OM001操纵子的缺失会降低在人唾液中的存活率。有研究表明在人唾液中的存活可能对传播很重要，这项研究将Spd1836和Spd1838确定为传播因子，可能促进肺炎链球菌在人与人之间的传播。总体而言，这项研究希望能进一步加深我们对疾病和疫情爆发之前细菌传播的理解。
