Neisseria gonorrhoeae is a multidrug-resistant bacterial pathogen for which ceftriaxone is the only remaining recommended first-line therapy.However,ceftriaxone susceptibility has been waning in a number of countries ...Neisseria gonorrhoeae is a multidrug-resistant bacterial pathogen for which ceftriaxone is the only remaining recommended first-line therapy.However,ceftriaxone susceptibility has been waning in a number of countries over the last decade and ceftriaxone treatment failures have been reported,commonly as a result of sporadic high-level ceftriaxone-resistant strains.In recent years,N.gonorrhoeae strains associated with the high-level ceftriaxone-resistant FC428 clone or strains that acquired its main ceftriaxone resistance determinant,penA allele 60.001,have shown global transmission,resulting in ceftriaxone treatment failure in a number of cases.The FC428 clone was first encountered in Japan in 2015 and subsequently in China,Europe,Australia,North America and Southeast Asia afterward.Strains associated with the FC428 clone commonly display a ceftriaxone minimum inhibitory concentration of 0.5-1 mg/L.However,where penA alleles encountered in sporadic high-level ceftriaxone-resistant isolates induce an in vitro growth defect,penA allele 60.001 does not seem to affect in vitro growth.The limited impact of penA allele 60.001 on biological fitness might be associated with its successful global transmission.Although the FC428 clone displays high-level ceftriaxone resistance,most gonorrhea cases associatedwith this clone were still successfully curedwith ceftriaxonewhen intramuscular or intravenous doses of 500mg to 2 g were used.A successful alternative therapy seems to be ertapenem given at 1-g doses,although further clinical studies are required to validate ertapenemefficacy.This review summarizes the global transmission of strains associated with the FC428 clone and antimicrobial treatment of associated cases.展开更多
Since the start of the outbreak of coronavirus disease 2019(COVID-19)in January 2020,the pandemic has been raging on for 3 years,with a devastating impact on human health,resulting globally in 663,248,631 confirmed in...Since the start of the outbreak of coronavirus disease 2019(COVID-19)in January 2020,the pandemic has been raging on for 3 years,with a devastating impact on human health,resulting globally in 663,248,631 confirmed infections and 6,709,387 confirmed deaths as of January 19,2023.1 Facing this remarkably fast developing pandemic with limited knowledge on many aspects of the disease,including transmission,effective infection control,morbidity and treatment,researchers and practitioners worldwide have switched their focus to COVID-19–related research and practices.According to incomplete statistics,more than 330,000 COVID-19–related publications have been indexed in PubMed by January 19,2023,2 which carried out comprehensive and multifaceted studies on COVID-19.These research findings have played a key role in controlling the spread of COVID-19,treating severe and/or critical cases,and reducing the morbidity and mortality.展开更多
Acetylcholinesterase(AChE) is a key enzyme used to detect organophosphorus pesticide residues by the enzyme inhibition method.An accidental discovery of a mutant strain with AChE activity was made in our laboratory du...Acetylcholinesterase(AChE) is a key enzyme used to detect organophosphorus pesticide residues by the enzyme inhibition method.An accidental discovery of a mutant strain with AChE activity was made in our laboratory during the process of AChE expression by Pichia pastoris.The pPIC9 K-Drosophila melanogaster acetylcholinesterase(DmAChE)-like expression vector was constructed by codon optimization of this mutant strain,which was transformed into P.pastoris GS115,and positive clones were selected on yeast peptone dextrose(YPD) plate with G418 at 4.0 mg/mL.The GS115-pPIC9 K-DmAChE-like strain was subjected to 0.5% methanol induction expression for 120 h,with a protein band at 4.3 kDa found by the tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE) pattern of the fermentation supernatant.After preliminary purification by ammonium sulfate precipitation,the enzyme activity was detected to be 76.9 U/(mL·min).In addition,the pesticide sensitivity test proved that DmAChE-like is selective and sensitive to organophosphorus pesticides.展开更多
Despite numerous studies on transcriptional level regulation by single genes in drug producing Actinomyces,the global regulation based on epigenetic modification is not well explored.N4-methylcytosine(m4C),an abundant...Despite numerous studies on transcriptional level regulation by single genes in drug producing Actinomyces,the global regulation based on epigenetic modification is not well explored.N4-methylcytosine(m4C),an abundant epigenetic marker in Actinomycetes’genome,but its regulatory mechanism remains unclear.In this study,we identify a m4C methyltransferase(SroLm3)in Streptomyces roseosporus L30 and multi-omics studies were performed and revealed SroLm3 as a global regulator of secondary metabolism.Notably,three BGCs inΔsroLm3 strain exhibited decreased expression compared to wild type.In-frame deletion of sroLm3 in S.roseosporus L30 further revealed its role in enhancing daptomycin production.In summary,we characterized a m4C methyltransferase,revealed the function of m4C in secondary metabolism regulation and biosynthesis of red pigment,and mapped a series of novel regulators for daptomycin biosynthesis dominated by m4C methylation.Our research further indicated that m4C DNA methylation may contribute to a metabolic switch from primary to secondary metabolism in Actinomyces.展开更多
基金supported by the National Natural Science Foundation of China(grant numbers 82272382,82150610507,82072320,81871695).
文摘Neisseria gonorrhoeae is a multidrug-resistant bacterial pathogen for which ceftriaxone is the only remaining recommended first-line therapy.However,ceftriaxone susceptibility has been waning in a number of countries over the last decade and ceftriaxone treatment failures have been reported,commonly as a result of sporadic high-level ceftriaxone-resistant strains.In recent years,N.gonorrhoeae strains associated with the high-level ceftriaxone-resistant FC428 clone or strains that acquired its main ceftriaxone resistance determinant,penA allele 60.001,have shown global transmission,resulting in ceftriaxone treatment failure in a number of cases.The FC428 clone was first encountered in Japan in 2015 and subsequently in China,Europe,Australia,North America and Southeast Asia afterward.Strains associated with the FC428 clone commonly display a ceftriaxone minimum inhibitory concentration of 0.5-1 mg/L.However,where penA alleles encountered in sporadic high-level ceftriaxone-resistant isolates induce an in vitro growth defect,penA allele 60.001 does not seem to affect in vitro growth.The limited impact of penA allele 60.001 on biological fitness might be associated with its successful global transmission.Although the FC428 clone displays high-level ceftriaxone resistance,most gonorrhea cases associatedwith this clone were still successfully curedwith ceftriaxonewhen intramuscular or intravenous doses of 500mg to 2 g were used.A successful alternative therapy seems to be ertapenem given at 1-g doses,although further clinical studies are required to validate ertapenemefficacy.This review summarizes the global transmission of strains associated with the FC428 clone and antimicrobial treatment of associated cases.
文摘Since the start of the outbreak of coronavirus disease 2019(COVID-19)in January 2020,the pandemic has been raging on for 3 years,with a devastating impact on human health,resulting globally in 663,248,631 confirmed infections and 6,709,387 confirmed deaths as of January 19,2023.1 Facing this remarkably fast developing pandemic with limited knowledge on many aspects of the disease,including transmission,effective infection control,morbidity and treatment,researchers and practitioners worldwide have switched their focus to COVID-19–related research and practices.According to incomplete statistics,more than 330,000 COVID-19–related publications have been indexed in PubMed by January 19,2023,2 which carried out comprehensive and multifaceted studies on COVID-19.These research findings have played a key role in controlling the spread of COVID-19,treating severe and/or critical cases,and reducing the morbidity and mortality.
基金supported by the National Development and Reform Commission of China(No.20111158)。
文摘Acetylcholinesterase(AChE) is a key enzyme used to detect organophosphorus pesticide residues by the enzyme inhibition method.An accidental discovery of a mutant strain with AChE activity was made in our laboratory during the process of AChE expression by Pichia pastoris.The pPIC9 K-Drosophila melanogaster acetylcholinesterase(DmAChE)-like expression vector was constructed by codon optimization of this mutant strain,which was transformed into P.pastoris GS115,and positive clones were selected on yeast peptone dextrose(YPD) plate with G418 at 4.0 mg/mL.The GS115-pPIC9 K-DmAChE-like strain was subjected to 0.5% methanol induction expression for 120 h,with a protein band at 4.3 kDa found by the tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE) pattern of the fermentation supernatant.After preliminary purification by ammonium sulfate precipitation,the enzyme activity was detected to be 76.9 U/(mL·min).In addition,the pesticide sensitivity test proved that DmAChE-like is selective and sensitive to organophosphorus pesticides.
基金supported by the National Natural Science Foundation of China(32141001 and 31830001)the National Science Fund for Distinguished Young Scholars(32125003)the National Key R&D Program of China(2022YFC2303900 and 2022YFC3704700)。
基金This work was supported by National Natural Science Foundation of China(grant number 31730002,2170057)the National Key R&D Program of China(grant number 2019YFA09005400)。
文摘Despite numerous studies on transcriptional level regulation by single genes in drug producing Actinomyces,the global regulation based on epigenetic modification is not well explored.N4-methylcytosine(m4C),an abundant epigenetic marker in Actinomycetes’genome,but its regulatory mechanism remains unclear.In this study,we identify a m4C methyltransferase(SroLm3)in Streptomyces roseosporus L30 and multi-omics studies were performed and revealed SroLm3 as a global regulator of secondary metabolism.Notably,three BGCs inΔsroLm3 strain exhibited decreased expression compared to wild type.In-frame deletion of sroLm3 in S.roseosporus L30 further revealed its role in enhancing daptomycin production.In summary,we characterized a m4C methyltransferase,revealed the function of m4C in secondary metabolism regulation and biosynthesis of red pigment,and mapped a series of novel regulators for daptomycin biosynthesis dominated by m4C methylation.Our research further indicated that m4C DNA methylation may contribute to a metabolic switch from primary to secondary metabolism in Actinomyces.
