Kim Jeong Nam, Ahn Sang-Joon, Burne Robert A
Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, Florida, USA.
Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, Florida, USA
Appl Environ Microbiol. 2015 Aug;81(15):5015-25. doi: 10.1128/AEM.01160-15. Epub 2015 May 15.
In the dental caries pathogen Streptococcus mutans, phosphotransacetylase (Pta) catalyzes the conversion of acetyl coenzyme A (acetyl-CoA) to acetyl phosphate (AcP), which can be converted to acetate by acetate kinase (Ack), with the concomitant generation of ATP. A ΔackA mutant displayed enhanced accumulation of AcP under aerobic conditions, whereas little or no AcP was observed in the Δpta or Δpta ΔackA mutant. The Δpta and Δpta ΔackA mutants also had diminished ATP pools compared to the size of the ATP pool for the parental or ΔackA strain. Surprisingly, when exposed to oxidative stress, the Δpta ΔackA strain appeared to regain the capacity to produce AcP, with a concurrent increase in the size of the ATP pool compared to that for the parental strain. The ΔackA and Δpta ΔackA mutants exhibited enhanced (p)ppGpp accumulation, whereas the strain lacking Pta produced less (p)ppGpp than the wild-type strain. The ΔackA and Δpta ΔackA mutants displayed global changes in gene expression, as assessed by microarrays. All strains lacking Pta, which had defects in AcP production under aerobic conditions, were impaired in their abilities to form biofilms when glucose was the growth carbohydrate. Collectively, these data demonstrate the complex regulation of the Pta-Ack pathway and critical roles for these enzymes in processes that appear to be essential for the persistence and pathogenesis of S. mutans.
在致龋病原体变形链球菌中，磷酸转乙酰酶（Pta）催化乙酰辅酶A（acetyl-CoA）转化为乙酰磷酸（AcP），乙酰磷酸可由乙酸激酶（Ack）转化为乙酸，同时生成ATP。ΔackA突变体在有氧条件下显示出AcP积累增强，而在Δpta或Δpta ΔackA突变体中几乎未观察到AcP。与亲本菌株或ΔackA菌株的ATP池大小相比，Δpta和Δpta ΔackA突变体的ATP池也有所减少。令人惊讶的是，当暴露于氧化应激时，Δpta ΔackA菌株似乎恢复了产生AcP的能力，与亲本菌株相比，ATP池大小同时增加。ΔackA和Δpta ΔackA突变体表现出增强的（p）ppGpp积累，而缺乏Pta的菌株产生的（p）ppGpp比野生型菌株少。通过微阵列评估，ΔackA和Δpta ΔackA突变体在基因表达上表现出全局变化。所有缺乏Pta的菌株在有氧条件下AcP产生存在缺陷，当葡萄糖作为生长碳水化合物时，它们形成生物膜的能力受损。总体而言，这些数据证明了Pta-Ack途径的复杂调控以及这些酶在变形链球菌的持续存在和致病过程中似乎至关重要的作用。
