Institute for Glycomics, Griffith University, Gold Coast, Queensland, 4215, Australia.
Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, 4006, Australia.
Sci Rep. 2019 Feb 22;9(1):2579. doi: 10.1038/s41598-019-39374-0.
Moraxella catarrhalis is a host-adapted bacterial pathogen that causes otitis media and exacerbations of chronic obstructive pulmonary disease. This study characterises the conserved M. catarrhalis extracellular nuclease, a member of the ββα metal finger family of nucleases, that we have named NucM. NucM shares conserved sequence motifs from the ββα nuclease family, including the DRGH catalytic core and Mg co-ordination site, but otherwise shares little primary sequence identity with other family members, such as the Serratia Nuc and pneumococcal EndA nucleases. NucM is secreted from the cell and digests linear and circular nucleic acid. However, it appears that a proportion of NucM is also associated with the cell membrane and acts as an entry nuclease, facilitating transformation of M. catarrhalis cells. This is the first example of a ββα nuclease in a Gram negative bacteria that acts as an entry nuclease. In addition to its role in competence, NucM affects cell aggregation and biofilm formation by M. catarrhalis, with ΔnucM mutants having increased biofilm biomass. NucM is likely to increase the ability of cells to survive and persist in vivo, increasing the virulence of M. catarrhalis and potentially affecting the behaviour of other pathogens that co-colonise the otorhinolaryngological niche.
卡他莫拉菌是一种宿主适应性细菌病原体,可引起中耳炎和慢性阻塞性肺疾病恶化。本研究对卡他莫拉菌保守的细胞外核酸酶进行了特征描述,该核酸酶属于ββα 金属指状家族的核酸酶,我们将其命名为 NucM。NucM 与ββα 核酸酶家族具有保守的序列基序,包括 DRGH 催化核心和 Mg 配位位点,但与其他家族成员(如沙雷氏菌 Nuc 和肺炎链球菌 EndA 核酸酶)的一级序列同一性较低。NucM 从细胞中分泌出来并消化线性和环状核酸。然而,似乎有一部分 NucM 也与细胞膜相关,并作为进入核酸酶发挥作用,促进卡他莫拉菌细胞的转化。这是革兰氏阴性菌中首例作为进入核酸酶的ββα 核酸酶。除了在感受态中的作用外,NucM 还影响卡他莫拉菌的细胞聚集和生物膜形成,ΔnucM 突变体的生物膜生物量增加。NucM 可能会增加细胞在体内生存和持续存在的能力,从而增加卡他莫拉菌的毒力,并可能影响其他共同定殖耳鼻喉科部位的病原体的行为。