Gardnerella vaginalis Subgroups Defined by cpn60 Sequencing and Sialidase Activity in Isolates from Canada,Belgium and Kenya

Increased abundance of Gardnerella vaginalis and sialidase activity in vaginal fluid is associated with bacterial vaginosis (BV), a common but poorly understood clinical entity associated with poor reproductive health outcomes. Since most women are colonized with G. vaginalis, its status as a normal member of the vaginal microbiota or pathogen causing BV remains controversial, and numerous classification schemes have been described. Since 2005, sequencing of the chaperonin-60 universal target (cpn60 UT) has distinguished four subgroups in isolate collections, clone libraries and deep sequencing datasets. To clarify potential clinical and diagnostic significance of cpn60 subgroups, we undertook phenotypic and molecular characterization of 112 G. vaginalis isolates from three continents. A total of 36 subgroup A, 33 B, 35 C and 8 D isolates were identified through phylogenetic analysis of cpn60 sequences as corresponding to four “clades” identified in a recently published study, based on sequencing 473 genes across 17 isolates. cpn60 subgroups were compared with other previously described molecular methods for classification of Gardnerella subgroups, including amplified ribosomal DNA restriction analysis (ARDRA) and real-time PCR assays designed to quantify subgroups in vaginal samples. Although two ARDRA patterns were observed in isolates, each was observed in three cpn60 subgroups (A/B/D and B/C/D). Real-time PCR assays corroborated cpn60 subgroups overall, but 13 isolates from subgroups A, B and D were negative in all assays. A putative sialidase gene was detected in all subgroup B, C and D isolates, but only in a single subgroup A isolate. In contrast, sialidase activity was observed in all subgroup B isolates, 3 (9%) subgroup C isolates and no subgroup A or D isolates. These observations suggest distinct roles for G. vaginalis subgroups in BV pathogenesis. We conclude that cpn60 UT sequencing is a robust approach for defining G. vaginalis subgroups within the vaginal microbiome.     

羊毛硫肽类化合物(Lanthipeptide)生物合成新进展

羊毛硫肽化合物(Lanthipeptides)是由核糖体合成并经过翻译后修饰得到的一大类肽类天然产物。这类化合物广泛的产生于不同种类的细菌,具有丰富的结构和生物活性多样性,为活性药物研究和开发提供重要的来源。本文综述了近几年来羊毛硫肽化合物生物合成进展,从其合成酶结构,进化机制,区域和立体选择性控制等方面进行了简要的讨论,展示了羊毛硫肽类化合物生物合成中特殊而迷人的酶学机制。     

AMPK activation protects cells from oxidative stress‐induced senescence via autophagic flux restoration and intracellular NAD+ elevation

AMPK activation is beneficial for cellular homeostasis and senescence prevention. However, the molecular events involved in AMPK activation are not well defined. In this study, we addressed the mechanism underlying the protective effect of AMPK on oxidative stress‐induced senescence. The results showed that AMPK was inactivated in senescent cells. However, pharmacological activation of AMPK by metformin and berberine significantly prevented the development of senescence and, accordingly, inhibition of AMPK by Compound C was accelerated. Importantly, AMPK activation prevented hydrogen peroxide‐induced impairment of the autophagic flux in senescent cells, evidenced by the decreased p62 degradation, GFP‐RFP‐LC3 cancellation, and activity of lysosomal hydrolases. We also found that AMPK activation restored the NAD⁺ levels in the senescent cells via a mechanism involving mostly the salvage pathway for NAD⁺ synthesis. In addition, the mechanistic relationship of autophagic flux and NAD⁺ synthesis and the involvement of mTOR and Sirt1 activities were assessed. In summary, our results suggest that AMPK prevents oxidative stress‐induced senescence by improving autophagic flux and NAD⁺ homeostasis. This study provides a new insight for exploring the mechanisms of aging, autophagy and NAD⁺ homeostasis, and it is also valuable in the development of innovative strategies to combat aging.     

Crystal Structural Framework of Lithium Super‐Ionic Conductors

As technologically important materials for solid‐state batteries, Li super‐ionic conductors are a class of materials exhibiting exceptionally high ionic conductivity at room temperature. These materials have unique crystal structural frameworks hosting a highly conductive Li sublattice. However, it is not understood why certain crystal structures of the super‐ionic conductors lead to high conductivity in the Li sublattice. In this study, using topological analysis and ab initio molecular dynamics simulations, the crystal structures of all Li‐conducting oxides and sulfides are studied systematically and the key features pertaining to fast‐ion conduction are quantified. In particular, a unique feature of enlarged Li sites caused by large local spaces in the crystal structural framework is identified, promoting fast conduction in the Li‐ion sublattice. Based on these quantified features, the high‐throughput screening identifies many new structures as fast Li‐ion conductors, which are further confirmed by ab initio molecular dynamics simulations. This study provides new insights and a systematic quantitative understanding of the crystal structural frameworks of fast ion‐conductor materials and motivates future experimental and computational studies on new fast‐ion conductors.