Acinetobacter baumannii(A.baumannii)is well known for its virulence and persistence,particularly in intensive care units.Therefore,new strategies and candidates to treat A.baumannii infection are urgently needed consi...Acinetobacter baumannii(A.baumannii)is well known for its virulence and persistence,particularly in intensive care units.Therefore,new strategies and candidates to treat A.baumannii infection are urgently needed considering the emergence of drug-resistant bacteria.Polyphosphate kinase 1(PPK1)is required for bacterial survival as it is involved in maintaining antibiotic resistance or tolerance,pathogenesis,and adversity resistance.Multiple phenotypic assays related to virulence and persistence were performed in this study,and phloretin was shown to attenuate A.baumannii virulence and persistence by inhibiting PPK1 activity.Phloretin hampered mobility,interfered with biofilm formation and decreased resistance to ampicillin,heat,and hydrogen peroxide stress in A.baumannii.The therapeutic effect was also examined in a mouse pneumonia infection model.Molecular simulation and site-directed mutagenesis revealed that ARG-22,MET-622,ASN-57,and ARG-65 were the sites of phloretin action against PPK1.Phloretin treatment led to changes in metabolic pathways associated with A.baumannii virulence and persistence,including glycerophospholipid metabolism and fatty acid biosynthesis.Furthermore,phloretin alleviated pneumonic injury in a mouse pneumonia infection model in vivo,indicating that phloretin is a promising compound for preventing A.baumannii infection resistance by targeting PPK1.展开更多
Inositol 1,4,5-trisphosphate 3-kinase(IP33-kinase/IP3K)plays an important role in signal transduction in animal cellsby phosphorylating inositol 1,4,5-trisphosphate(IP3)to inositol 1,3,4,5-tetrakisphosphate(IP4).Both ...Inositol 1,4,5-trisphosphate 3-kinase(IP33-kinase/IP3K)plays an important role in signal transduction in animal cellsby phosphorylating inositol 1,4,5-trisphosphate(IP3)to inositol 1,3,4,5-tetrakisphosphate(IP4).Both IP3 and IP4 arecritical second messengers which regulate calcium(Ca2+)homeostasis.Mammalian IP3Ks are involved in many biologicalprocesses,including brain development,memory,learning and so on.It is widely reported that Ca2+is a canonicalsecond messenger in higher plants.Therefore,plant IP3K should also play a crucial role in plant development.Recently,we reported the identification of plant IP3K gene(AtIpk2β/AtIP3K)from Arabidopsis thaliana and its characterization.Here,we summarize the molecular cloning,biochemical properties and biological functions of IP3Ks from animal,yeastand plant.This review also discusses potential functions of IP3Ks in signaling crosstalk,inositol phosphate metabolism,gene transcriptional control and so on.展开更多
Candidatus Accumulibacter has been identified as dominant polyphosphate-accumulating organisms（PAOs） in enhanced biological phosphorus（P） removal（EBPR） from wastewater.This study revealed the relevance of commun...Candidatus Accumulibacter has been identified as dominant polyphosphate-accumulating organisms（PAOs） in enhanced biological phosphorus（P） removal（EBPR） from wastewater.This study revealed the relevance of community structure, abundance and seasonal population dynamics of Candidatus Accumulibacter to process operation of wastewater treatment plants（WWTPs） in China using ppk1 gene as phylogenetic marker. All sludge samples had properties of denitrifying P removal using nitrate as an electron acceptor.Accumulibacter abundance in the anaerobic-anoxic-oxic（A^2O） process was the highest（26%of total bacteria）, and higher in winter than in summer with a better EBPR performance.Type-II was the dominant Accumulibacter in all processes, and type-I accounted for a small proportion of total Accumulibacter. The abundance of Clade-IIC as the most dominant clade reached 2.59 × 10~9 cells/g MLSS and accounted for 87.3% of total Accumulibacter. Clade IIC mainly contributed to denitrifying P removal. Clades IIA, IIC and IID were found in all processes, while clade-IIF was only found in oxidation ditch process through phylogenetic analysis. High proportion of clade IID to total Accumulibacter led to poor performance of aerobic P-uptake in inverted A^2O process. Therefore, Accumulibacter clades in WWTPs were diverse, and EBPR performance was closely related to the clade-level community structures and abundances of Accumulibacter.展开更多
Candidatus Accumulibacter,a prominent polyphosphate-accumulating organism(PAO)in wastewater treatment,plays a crucial role in enhanced biological phosphorus removal(EBPR).The genetic underpinnings of its polyphosphate...Candidatus Accumulibacter,a prominent polyphosphate-accumulating organism(PAO)in wastewater treatment,plays a crucial role in enhanced biological phosphorus removal(EBPR).The genetic underpinnings of its polyphosphate accumulation capabilities,however,remain largely unknown.Here,we conducted a comprehensive genomic analysis of Ca.Accumulibacter-PAOs and their relatives within the Rhodocyclaceae family,identifying 124 core genes acquired via horizontal gene transfer(HGT)at its least common ancestor.Metatranscriptomic analysis of an enrichment culture of Ca.Accumulibacter revealed active transcription of 44 of these genes during an EBPR cycle,notably including the polyphosphate kinase 2(PPK2)gene instead of the commonly recognized polyphosphate kinase 1(PPK1)gene.Intriguingly,the phosphate regulon(Pho)genes showed minimal transcriptions,pointing to a distinctive fact of Pho dysregulation,where PhoU,the phosphate signaling complex protein,was not regulating the high-affinity phosphate transport(Pst)system,resulting in continuous phosphate uptake.To prevent phosphate toxicity,Ca.Accumulibacter utilized the laterally acquired PPK2 to condense phosphate into polyphosphate,resulting in the polyphosphate-accumulating feature.This study provides novel insights into the evolutionary emergence of the polyphosphate-accumulating trait in Ca.Accumulibacter,offering potential advancements in understanding the PAO phenotype in the EBPR process.展开更多
基金supported by the National Natural Science Foundation of China(U23A20242 and U22A20523)the Fundamental Research Funds for the Central Universities under Grant 2023JCXK-01。
文摘Acinetobacter baumannii(A.baumannii)is well known for its virulence and persistence,particularly in intensive care units.Therefore,new strategies and candidates to treat A.baumannii infection are urgently needed considering the emergence of drug-resistant bacteria.Polyphosphate kinase 1(PPK1)is required for bacterial survival as it is involved in maintaining antibiotic resistance or tolerance,pathogenesis,and adversity resistance.Multiple phenotypic assays related to virulence and persistence were performed in this study,and phloretin was shown to attenuate A.baumannii virulence and persistence by inhibiting PPK1 activity.Phloretin hampered mobility,interfered with biofilm formation and decreased resistance to ampicillin,heat,and hydrogen peroxide stress in A.baumannii.The therapeutic effect was also examined in a mouse pneumonia infection model.Molecular simulation and site-directed mutagenesis revealed that ARG-22,MET-622,ASN-57,and ARG-65 were the sites of phloretin action against PPK1.Phloretin treatment led to changes in metabolic pathways associated with A.baumannii virulence and persistence,including glycerophospholipid metabolism and fatty acid biosynthesis.Furthermore,phloretin alleviated pneumonic injury in a mouse pneumonia infection model in vivo,indicating that phloretin is a promising compound for preventing A.baumannii infection resistance by targeting PPK1.
基金supported by grants from the National Natural Science Foundation of China(No.30370142)the National Special Key Project on Functional Genomics and Biochip of China(No.2002AA2Z1002)the Project sponsored by the Scientific Research Foundation for the Returned Oversea Chinese Scholars,State Education Ministry.
文摘Inositol 1,4,5-trisphosphate 3-kinase(IP33-kinase/IP3K)plays an important role in signal transduction in animal cellsby phosphorylating inositol 1,4,5-trisphosphate(IP3)to inositol 1,3,4,5-tetrakisphosphate(IP4).Both IP3 and IP4 arecritical second messengers which regulate calcium(Ca2+)homeostasis.Mammalian IP3Ks are involved in many biologicalprocesses,including brain development,memory,learning and so on.It is widely reported that Ca2+is a canonicalsecond messenger in higher plants.Therefore,plant IP3K should also play a crucial role in plant development.Recently,we reported the identification of plant IP3K gene(AtIpk2β/AtIP3K)from Arabidopsis thaliana and its characterization.Here,we summarize the molecular cloning,biochemical properties and biological functions of IP3Ks from animal,yeastand plant.This review also discusses potential functions of IP3Ks in signaling crosstalk,inositol phosphate metabolism,gene transcriptional control and so on.
基金supported by the National Key Research and Development Programme of China (No. 2016YFC0401103)the Natural Science Foundation of China (No. 51578016)the Natural Science Foundation of Beijing (No. 8172014)
文摘Candidatus Accumulibacter has been identified as dominant polyphosphate-accumulating organisms（PAOs） in enhanced biological phosphorus（P） removal（EBPR） from wastewater.This study revealed the relevance of community structure, abundance and seasonal population dynamics of Candidatus Accumulibacter to process operation of wastewater treatment plants（WWTPs） in China using ppk1 gene as phylogenetic marker. All sludge samples had properties of denitrifying P removal using nitrate as an electron acceptor.Accumulibacter abundance in the anaerobic-anoxic-oxic（A^2O） process was the highest（26%of total bacteria）, and higher in winter than in summer with a better EBPR performance.Type-II was the dominant Accumulibacter in all processes, and type-I accounted for a small proportion of total Accumulibacter. The abundance of Clade-IIC as the most dominant clade reached 2.59 × 10~9 cells/g MLSS and accounted for 87.3% of total Accumulibacter. Clade IIC mainly contributed to denitrifying P removal. Clades IIA, IIC and IID were found in all processes, while clade-IIF was only found in oxidation ditch process through phylogenetic analysis. High proportion of clade IID to total Accumulibacter led to poor performance of aerobic P-uptake in inverted A^2O process. Therefore, Accumulibacter clades in WWTPs were diverse, and EBPR performance was closely related to the clade-level community structures and abundances of Accumulibacter.
基金supported by the National Natural Science Foundation of China(52270035 and 51808297)the Natural Science Foundation of Guangdong Province(2021A1515010494)+1 种基金the Guangzhou Key Research and Development Program(2023B03J1334)the Pearl River Talent Recruitment Program(2019QN01L125).
文摘Candidatus Accumulibacter,a prominent polyphosphate-accumulating organism(PAO)in wastewater treatment,plays a crucial role in enhanced biological phosphorus removal(EBPR).The genetic underpinnings of its polyphosphate accumulation capabilities,however,remain largely unknown.Here,we conducted a comprehensive genomic analysis of Ca.Accumulibacter-PAOs and their relatives within the Rhodocyclaceae family,identifying 124 core genes acquired via horizontal gene transfer(HGT)at its least common ancestor.Metatranscriptomic analysis of an enrichment culture of Ca.Accumulibacter revealed active transcription of 44 of these genes during an EBPR cycle,notably including the polyphosphate kinase 2(PPK2)gene instead of the commonly recognized polyphosphate kinase 1(PPK1)gene.Intriguingly,the phosphate regulon(Pho)genes showed minimal transcriptions,pointing to a distinctive fact of Pho dysregulation,where PhoU,the phosphate signaling complex protein,was not regulating the high-affinity phosphate transport(Pst)system,resulting in continuous phosphate uptake.To prevent phosphate toxicity,Ca.Accumulibacter utilized the laterally acquired PPK2 to condense phosphate into polyphosphate,resulting in the polyphosphate-accumulating feature.This study provides novel insights into the evolutionary emergence of the polyphosphate-accumulating trait in Ca.Accumulibacter,offering potential advancements in understanding the PAO phenotype in the EBPR process.
