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| 1 | In vitro and in vivo activity of D-serine in combination with β-lactam antibiotics against methicillin-resistant Staphylococcus aureus显示文摘As D-amino acids play important roles in the physiological metabolism of bacteria,combination of D-amino acids with antibiotics may provide synergistic antibacterial activity. The aim of the study was to evaluate in vitro and in vivo activity of D-serine alone and in combination withβ-lactams against methicillin-resistant Staphylococcus aureus(MRSA) strains, and to explore the possible sensitization mechanisms. The activity of D-serine, β-lactams alone and in combinations was evaluated both in vitro by standard MICs, time–kill curves and checkerboard assays, and in vivo by murine systemic infection model as well as neutropenic thigh infection model. An in vitro synergistic effect was demonstrated with the combination of D-serine and β-lactams against MRSA standard and clinical strains.Importantly, the combinations enhanced the therapeutic efficacy in the animal models as compared toβ-lactam alone groups. Initial mechanism study suggested possible revision of D-alanine-D-alanine residue to D-alanine-D-serine in peptidoglycan by adding of D-alanine in the medium, which may cause decreased affinity to PBPs during transpeptidation. In conclusion, D-serine had synergistic activity in combination with β-lactams against MRSA strains both in vitro and in vivo. Considering the relatively good safety of D-serine alone or in combination with β-lactams, D-serine is worth following up as new anti-MRSA infection strategies. | Qing Wang Yuemeng Lv Jing Pang Xue Li Xi Lu Xiukun Wang Xinxin Hu Tongying Nie Xinyi Yang Yan Q.Xiong Jiandong Jiang Congran Li Xuefu You | 2019 | Acta Pharmaceutica Sinica B2019，9，3： | 6 |
| 2 | Genetic basis of high level aminoglycoside resistance in Acinetobacter baumannii from Beijing,China显示文摘The objective of this study was to investigate the genetic basis of high level aminoglycoside resistance in Acinetobacter baumannii clinical isolates from Beijing,China.173 A.baumannii clinical isolates from hospitals in Beijing from 2006 to 2009 were first subjected to high level aminoglycoside resistance(HLAR,MIC to gentamicin and amikacin>512 mg/mL)phenotype selection by broth microdilution method.The strains were then subjected to genetic basis analysis by PCR detection of the aminoglycoside modifying enzyme genes(aac(3)-Ⅰ,aac(3)-Ⅱc,aac(60)-Ⅰb,aac(60)-Ⅱ,aph(4)-Ⅰa,aph(30)-Ⅰ,aph(30)-Ⅱb,aph(30)-Ⅲa,aph(30)-Ⅵa,aph(2″)-Ⅰb,aph(2″)-Ⅰc,aph(2″)-Ⅰd,ant(2″)-Ⅰa,ant(3″)-Ⅰand ant(40)-Ⅰa)and the 16S rRNA methylase genes(armA,rmtB and rmtC).Correlation analysis between the presence of aminoglycoside resistance gene and HLAR phenotype were performed by SPSS.Totally 102(58.96%)HLAR isolates were selected.The HLAR rates for year 2006,2007,2008 and 2009 were 52.63%,65.22%,51.11%and 70.83%,respectively.Five modifying enzyme genes(aac(3)-Ⅰ,detection rate of 65.69%;aac(60)-Ⅰb,detection rate of 45.10%;aph(30)-Ⅰ,detection rate of 47.06%;aph(30)-Ⅱb,detection rate of 0.98%;ant(3″)-Ⅰ,detection rate of 95.10%)and one methylase gene(armA,detection rate of 98.04%)were detected in the 102 A.baumannii with aac(3)-Ⅰ+aac(60)-Ⅰ+þant(3″)-Ⅰ+armA(detection rate of 25.49%),aac(3)-Ⅰ+aph(30)-Ⅰ+ant(3″)-Ⅰ+armA(detection rate of 21.57%)and ant(3″)-Ⅰ+armA(detection rate of 12.75%)being the most prevalent gene profiles.The values of chi-square tests showed correlation of armA,ant(3″)-Ⅰ,aac(3)-Ⅰ,aph(30)-Ⅰand aac(60)-Ⅰb with HLAR.armA had significant correlation(contingency coefficient 0.685)and good contingency with HLAR(kappa 0.940).The high rates of HLAR may cause a serious problem for combination therapy of aminoglycoside with β-lactams against A.baumannii infections.As armA was reported to be able to cause high level aminoglycoside resistance to most of the clinical important aminoglycosides(gentamicin,amikacin,tobramycin,etc),the function of aminoglycoside modifying enzyme gene(s)in A.baumannii carrying armA deserves further investigation. | Lu Nie Yuemeng Lv Min Yuan Xinxin Hu Tongying Nie Xinyi Yang Guoqing Li Jing Pang Jingpu Zhang Congran Li Xiukun Wang Xuefu You | 2014 | Acta Pharmaceutica Sinica B2014，4，4： | 3 |
| 3 | Diversity, novelty, antimicrobial activity, and new antibiotics of cultivable endophytic actinobacteria isolated from psammophytes collected from Taklamakan Desert显示文摘Three hundred and twenty endophytic actinobacterial strains were isolated from psammophytes collected from Taklamakan Desert and identified. Among them, three strains already had been identified as new species of two genera and sixteen isolates showed relatively low 16 S rRNA similarities < 98.6% to validly described species. Seventy-five of the isolates were selected as representative strains to screen antibacterial activity and mechanism. Forty-seven strains showed antagonistic activity against at least one of the indicator bacteria. Two Streptomyces strains produced bioactive compounds inducing DNA damage, and two Streptomyces strains produced bioactive compounds with inhibitory activity on protein biosynthesis. Notably, the strain Streptomyces sp. 8P21H-1 that demonstrated both strong antibacterial activity and inhibitory activity on protein biosynthesis was prioritized for exploring new antibiotics.Under the strategy of integrating genetics-based discovery program and MS/MS-based molecular networking, two new streptogramin-type antibiotics, i.e., acetyl-griseoviridin and desulphurizing griseoviridin, along with known griseoviridin, were isolated from the culture broth of strain 8P21H-1. Their chemical structures were determined by HR-MS, and 1D and 2D NMR. Desulphurizing griseoviridin and griseoviridin exhibited antibacterial activities by inhibiting translation. | Ting Wang Feina Li Qinpei Lu Gang Wu Zhongke Jiang Shaowei Liu Xugela Habden Elizaveta A.Razumova Ilya A.Osterman Petr V.Sergiev Olga A.Dontsova Xinxin Hu Xuefu You Chenghang Sun | 2021 | Journal of Pharmaceutical Analysis2021，11，2： | 2 |
| 4 | Validated LC–MS/MS method for determination of YH-8, a novel PKnB inhibitor, in rat plasma and its application to pharmacokinetic study显示文摘(E)-Methyl-4-aryl-4-oxabut-2-enoate(YH-8) is a novel PKn B protein kinase inhibitor with good anti-tuberculosis activity. To evaluate its pharmacokinetics in rats, a sensitive and selective high performance liquid chromatography–tandem mass spectrometric(LC–MS/MS) method has been developed and validated for the quantification of YH-8 in rat plasma for the first time. Samples were pre-treated using a liquid–liquid extraction with ethyl acetate and the chromatographic separation was performed on a C18 column by gradient elution with methanol–water as the mobile phase. YH-8 was detected using a tandem mass spectrometer in positive selected reaction monitoring(SRM) mode. Method validation revealed good linearity over the range of1–500 ng/m L for YH-8 with a lower limit of quantification(LLOQ) of 1 ng/m L. Intra- and inter-day precision of YH-8 assay in rat plasma samples were 2.0%–6.8%, with accuracy of the method being 100.69%–106.18%.Stability test showed that when spiked into rat plasma, YH-8 was stable for 12 h at room temperature, for up to15 days at -70℃, and after three freeze-thaw cycles. Extracted samples were found to be stable over 12 h in an auto-sampler. The method was successfully applied to the pharmacokinetic study of YH-8 in rats after oral administration at 100 mg/kg and 200 mg/kg. | Qianqian Zhai Jing Pang Guoqing Li Congran Li Xinyi Yang Liyan Yu Yucheng Wang Jian Li Xuefu You | 2015 | Acta Pharmaceutica Sinica B2015，5，5： | 2 |
| 5 | Polymyxin resistance caused by large-scale genomic inversion due to IS26 intramolecular translocation in Klebsiella pneumoniae显示文摘Polymyxin B and polymyxin E(colistin)are presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales,Acinetobacter baumannii,and Klebsiella pneumoniae.Yet resistance to this last-line drugs is a major public health threat and is rapidly increasing.Polymyxin S2(S2)is a polymyxin B analogue previously synthesized in our institute with obviously high antibacterial activity and lower toxicity than polymyxin B and colistin.To predict the possible resistant mechanism of S2for wide clinical application,we experimentally induced bacterial resistant mutants and studied the preliminary resistance mechanisms.Mut-S,a resistant mutant of K.pneumoniae ATCC BAA-2146(Kpn2146)induced by S2,was analyzed by whole genome sequencing,transcriptomics,mass spectrometry and complementation experiment.Surprisingly,large-scale genomic inversion(LSGI)of approximately 1.1 Mbp in the chromosome caused by IS26mediated intramolecular transposition was found in Mut-S,which led to mgrB truncation,lipid A modification and hence S2resistance.The resistance can be complemented by plasmid carrying intact mgrB.The same mechanism was also found in polymyxin B and colistin induced drug-resistant mutants of Kpn2146(Mut-B and Mut-E,respectively).This is the first report of polymyxin resistance caused by IS26 intramolecular transposition mediated mgrB truncation in chromosome in K.pneumoniae.The findings broaden our scope of knowledge for polymyxin resistance and enriched our understanding of how bacteria can manage to survive in the presence of antibiotics. | Haibin Li Lang Sun Han Qiao Zongti Sun Penghe Wang Chunyang Xie Xinxin Hu Tongying Nie Xinyi Yang Guoqing Li Youwen Zhang Xiukun Wang Zhuorong Li Jiandong Jiang Congran Li Xuefu You | 2023 | Acta Pharmaceutica Sinica B2023，13，9： | 1 |
| 6 | Cyclic and Linear Thiopeptides from Soil-Derived Streptomyces sp.CPCC 203702 with Antiviral and Antibacterial Activities显示文摘A new cyclic thiopeptide,berninamycin F(3),three new linear thiopeptides,berninamycins G—I(4-6),and two known berninamycin derivatives,berninamycins C and D(1 and 2)were isolated from Streptomyces sp.CPCC 203702.Their structures were elucidated through HRESIMS and one-and two-dimensional NMR data,and the absolute configurations were assigned using Marfey's method.Compounds 4-6 are the first examples of linear berninamycin analogs.Notably,compound 4 is the first example of linear thiopeptide with a 1-(oxazol-2-yl)ethan-1-one group,compound 6 is the first linear thiopeptide derivative with methylated oxoacetate moiety.Compounds 1-6 exhibited excellent anti-Zika virus activities with IC_(50) values in the range of 4.4-10.5μmol/L,which were superior to that of the positive control ribavirin(IC_(50)=49.2μmol/L).Compounds 1 and 3 showed strong anti-influenza A virus activities with the IC_(50) values of 15.6 and 3.2μmol/L,respectively.Compound 1 exhibited good antibacterial activities against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus spp.pathogens. | Dewu Zhang Yujia Wang Xinxin Hu Xiaoyu Wang Linzi Li Guowei Gu Bingyuan Zhang Shan Cen Xuefu You Liyan Yu | 2021 | Chinese Journal of Chemistry2021，39，12： | 1 |
| 7 | Evolution and development of potent monobactam sulfonate candidate IMBZ18g as a dual inhibitor against MDR Gram-negative bacteria producing ESBLs显示文摘A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria.Compound 33a(IMBZ18G)is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant(MDR)Gram-negative strains,with a highly druglike nature.The checkerboard assay reveals its significant synergistic effect withβ-lactamase inhibitor avibactam,and the MIC values against MDR enterobacteria were reduced up to 4—512folds.X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and Cβ-lactamases.Accordingly,preclinical studies of 33a alone and 33a-avibactam combination as potential innovative candidates are actively going on,in the treatment ofβ-lactamase-producing MDR Gram-negative bacterial infections. | Zhiwen Li Zhihao Guo Xi Lu Xican Ma Xiukun Wang Rui Zhang Xinxin Hu Yanxiang Wang Jing Pang Tianyun Fan Yonghua Liu Sheng Tang Haigen Fu Jingpu Zhang Yinghong Li Xuefu You Danqing Song | 2023 | Acta Pharmaceutica Sinica B2023，13，7： | 0 |
| 8 | Coagulation factors: a novel class of endogenous host antimicrobial proteins against drug-resistant gram-negative bacteria显示文摘In a recent study published in Cell Research,Dr.Xu Song’s group reported the potent antibacterial activity of three coagulation factors(VII,IX,and X)against gram-negative bacteria and hence discovered a novel class of endogenous host antimicrobial proteins.1 At present,antimicrobial resistance(AMR)poses significant challenges for clinical care and seriously threatens human health.2,3 Among the clinical pathogens,gram-negative bacteria are particularly problematic in terms of drug resistance because their lipopolysaccharide(LPS)-rich outer membrane reduces cellular permeability and acts as a target for antibacterial resistance development. | Congran Li Xuefu You | 2019 | Signal Transduction and Targeted Therapy2019，4，1： | 0 |
| 9 | Probing surface structure on two-dimensional metal-organic layers to understand suppressed interlayer packing显示文摘Two-dimensional metal-organic layers(MOLs)from alternatively connected benzene-tribenzoate ligands and Zr6(μ3-O)_(4)(μ3-OH)_(4) or Hf6(μ3-O)_(4)(μ3-OH)_(4) secondary building units can be prepared in gram scale via solvothermal synthesis.However,the reason why the monolayers did not pack to form thick crystals is unknown.Here we investigated the surface structure of the MOLs by a combination of sum-frequency generation spectroscopy,nanoscale infrared microscopy,atomic force microscopy,aberration-corrected transmission electron microscopy,and compositional analysis.We found a partial coverage of the monolayer surface by dangling tricarboxylate ligands,which prevent packing of the monolayers.This finding illustrates low-density surface modification as a strategy to prepare new two-dimensional materials with a high percentage of exposed surface. | Peican Chen Yi Liu Xuefu Hu Xiaolin Liu En-Ming You Xudong Qian Jiawei Chen Liangping Xiao Lingyun Cao Xinxing Peng Zhongming Zeng Yibing Jiang Song-Yuan Ding Honggang Liao Zhaohui Wang Da Zhou Cheng Wang | 2020 | Nano Research2020，13，11： | 0 |
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