Current drug targets. Infectious disorders最新文献_第5页

Macrolide resistance based on the Erm-mediated rRNA methylation. 基于erm介导的rRNA甲基化的大环内酯耐药。

Current drug targets. Infectious disorders Pub Date : 2004-09-01 DOI: 10.2174/1568005043340777

G Maravić

{"title":"Macrolide resistance based on the Erm-mediated rRNA methylation.","authors":"G Maravić","doi":"10.2174/1568005043340777","DOIUrl":"https://doi.org/10.2174/1568005043340777","url":null,"abstract":"Macrolide, lincosamide and streptogramin B (MLSB) antibiotics are extensively used for the treatment of wide variety of clinically important Gram-positive bacteria. MLSB antibiotics inhibit protein biosynthesis by targeting the peptidyl transferase centre within the 50S ribosomal subunit. The most widespread mechanism of bacterial resistance to MLSB antibiotics, reported early after their introduction into clinical practice is the modification of the target site exhibited by a family of rRNA methyltransferases designated Erm. Using S-adenosyl-L-methionine, Erm enzymes catalyze mono- or dimethylation of a specific adenine residue in the 23S rRNA. The methyl group sterically hinders the MLSB binding site and disrupts the hydrogen bonding between the macrolides and the rRNA, thus rendering bacteria resistant. This review summarizes the current understanding of Erm-mediated resistance, in light of high-resolution structural data of bacterial ribosome and with specific focus on the results of recent genetic, biochemical and structural studies of Erm methyltransferases and their cognate rRNA substrate. Although many features of MLSB resistance remain indistinct, the present knowledge can now serve as the guidance for development of both new antimicrobial drugs and potential inhibitors of Erm enzymes, hence providing a new lead to solve the urgent problem of the macrolide resistance based on the ribosome methylation.","PeriodicalId":84525,"journal":{"name":"Current drug targets. Infectious disorders","volume":"4 3","pages":"193-202"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568005043340777","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24692943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 52

Inactivation of macrolides by producers and pathogens. 生产者和病原体对大环内酯类化合物的失活作用。

Current drug targets. Infectious disorders Pub Date : 2004-09-01 DOI: 10.2174/1568005043340696

Mayumi Matsuoka, Tsuguo Sasaki

{"title":"Inactivation of macrolides by producers and pathogens.","authors":"Mayumi Matsuoka, Tsuguo Sasaki","doi":"10.2174/1568005043340696","DOIUrl":"https://doi.org/10.2174/1568005043340696","url":null,"abstract":"Inactivation, one of the mechanisms of resistance to macrolide, lincosamide and streptogramin (MLS) antibiotics, appears to be fairly rare in clinical isolates in comparison with target site modification or efflux. However, inactivation is one of the major mechanisms through which macrolide-producing organisms avoid self-damage during antibiotic biosynthesis. The inactivation mechanisms for MLS antibiotics in pathogens are mainly hydrolysis, phosphorylation, glycosylation, reduction, deacylation, nucleotidylation, and acetylation. The ere (erythromycin resistance esterase) and mph (macrolide phosphotransferase) genes were originally found in Escherichia coli. Subsequently, Wondrack et al. (Wondrack, L.; Massa, M.; Yang, B.V.; Sutcliffe, J. Antimicrob. Agents Chemother., 1996, 40, 992) reported ere-like activity in Staphylococcus aureus. In addition, a variant of erythromycin esterase was found in Pseudomonas sp. from aquaculture sediment by Kim et al. (Kim, Y.H.; Cha, C.J.; Cerniglia, C.E. FEMS Microbiol. Lett., 2002, 210, 239). Although the mph genes, including mph(K), were first characterized in E. coli, a recent study revealed that S. aureus and Stenotrophomonas maltophilia have mph(C). The mph(C) has a low G+C content, like mph(B), and has high homology with mph(B), but not with mph(A) or mph(K). Consequently, the mph(C) and ere(B) genes seem to have originated from Gram-positive bacteria and been transferred between Gram-positive and Gram-negative bacteria. In this chapter, the genes and the mechanisms involved in the inactivation of MLS antibiotics by antibiotic-producing bacteria are reviewed.","PeriodicalId":84525,"journal":{"name":"Current drug targets. Infectious disorders","volume":"4 3","pages":"217-40"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568005043340696","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24692946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 35

Macrolide resistance in Streptococcus pneumoniae: clonality and mechanisms of resistance in 24 countries. 肺炎链球菌的大环内酯耐药:24个国家的克隆性和耐药机制

Current drug targets. Infectious disorders Pub Date : 2004-09-01 DOI: 10.2174/1568005043340821

Bülent Bozdogan, Tatiana Bogdanovich, Klaudia Kosowska, Michael R Jacobs, Peter C Appelbaum

{"title":"Macrolide resistance in Streptococcus pneumoniae: clonality and mechanisms of resistance in 24 countries.","authors":"Bülent Bozdogan, Tatiana Bogdanovich, Klaudia Kosowska, Michael R Jacobs, Peter C Appelbaum","doi":"10.2174/1568005043340821","DOIUrl":"https://doi.org/10.2174/1568005043340821","url":null,"abstract":"The clonality and mechanisms of macrolide resistance were studied among 345 macrolide resistant Streptococcus pneumoniae strains isolated from 24 countries. The mechanisms of macrolide resistance, serotypes and PFGE types of the strains were determined and representative strains of clones from each country were typed by MLST. Among strains tested 215 had the erm(B) gene, 92 the mef(A) gene, 14 had both erm(B) and mef(A), and 24 had alterations in ribosomal proteins [2 with A2059G substitutions in 23S rRNA, 21 with 69GTG71 to TPS change in L4, and one with erm(B) and deletion of leucine at position 68 in L22]. Serogroups 19, 6, and 23, and serotype 14 were the most common serotypes/serogroups. Dissemination of variants of sequence type (ST) 315 and ST156 were observed in Eastern and Central European countries. In Asiatic countries the most common sequence types were variants of ST236 among strains with mef(A) and ST180 among strains with erm(B). Strains with both erm(B) and mef(A) from Mexico and Singapore were variants of ST236. The widespread clone from Slovakia with ribosomal protein L4 mutation was a variant of ST226. Common clones were observed between Europe, Asia, and America. Overall, while serotypes/serogroups of macrolide resistant isolates were limited, multiple PFGE and MLST types were found, with clustering of common clones within countries.","PeriodicalId":84525,"journal":{"name":"Current drug targets. Infectious disorders","volume":"4 3","pages":"169-76"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24692941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 14

Genetic elements carrying macrolide efflux genes in streptococci. 链球菌中携带大环内酯外排基因的遗传元件。

Current drug targets. Infectious disorders Pub Date : 2004-09-01 DOI: 10.2174/1568005043340641

Gianni Pozzi, Francesco Iannelli, Marco R Oggioni, Maria Santagati, Stefania Stefani

引用次数: 37

Macrolide resistance from the ribosome perspective. 从核糖体角度看大环内酯类药物耐药性。

Current drug targets. Infectious disorders Pub Date : 2004-09-01 DOI: 10.2174/1568005043340740

F Franceschi, Z Kanyo, E C Sherer, J Sutcliffe

引用次数: 66

Preface [Hot Topic: Macrolide Resistance (Guest Editor: Joyce Sutcliffe)] 前言[热门话题:大环内酯类药物耐药性(客座编辑:Joyce Sutcliffe)]

Current drug targets. Infectious disorders Pub Date : 2004-08-31 DOI: 10.2174/15680053104040300II

J. Sutcliffe

引用次数: 0

Two orthogonal approaches to overcome multi-drug resistant HIV-1s: development of protease inhibitors and entry inhibitors based on CXCR4 antagonists. 克服多重耐药hiv -1的两种正交方法:开发蛋白酶抑制剂和基于CXCR4拮抗剂的进入抑制剂。

Current drug targets. Infectious disorders Pub Date : 2004-06-01 DOI: 10.2174/1568005043340957

Hirokazu Tamamura, Nobutaka Fujii

{"title":"Two orthogonal approaches to overcome multi-drug resistant HIV-1s: development of protease inhibitors and entry inhibitors based on CXCR4 antagonists.","authors":"Hirokazu Tamamura, Nobutaka Fujii","doi":"10.2174/1568005043340957","DOIUrl":"https://doi.org/10.2174/1568005043340957","url":null,"abstract":"The development of novel drugs active against multi-drug resistant (MDR) HIV-1 strains is urgently required. HIV protease inhibitors and reverse transcriptase inhibitors constitute two categories of important drugs, which have greatly improved the clinical treatment of HIV-infected patients by their cocktail use designated as highly active anti-retroviral therapy (HAART). By combinatorial chemistry involving substructure units contained in known HIV protease inhibitors, we found effective protease inhibitors, TYA5 and TYB5, which showed potent anti-HIV activity even against MDR strains. Selection of drug-resistant viruses is also decreased when these new agents are tested in vitro. Subsequently, introduction of an (E)-alkene dipeptide isostere into TYB5 led to the development of a pure non-peptide protease inhibitor, TYB1. We have also studied the development of effective inhibitors for blocking HIV-entry into host cells based on recent discovery of an HIV entry mechanism involving the viral usage of chemokine receptors as coreceptors, CXCR4 and CCR5. We developed highly selective CXCR4 antagonists, T22 and T140 (18-mer and 14-mer peptides, respectively), which strongly suppress T-cell line-tropic HIV-1 (X4-HIV-1) entry through their specific binding to CXCR4. Recently, molecular-size reduction of T140 yielded low molecular weight CXCR4 antagonists, which might be more useful leads to drug-like structures. In this review, we discuss the development of two types of anti-HIV agents, protease inhibitors and CXCR4 antagonists, which would improve clinical AIDS chemotherapy.","PeriodicalId":84525,"journal":{"name":"Current drug targets. Infectious disorders","volume":"4 2","pages":"103-10"},"PeriodicalIF":0.0,"publicationDate":"2004-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24552417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Antiviral properties of quinolone-based drugs. 喹诺酮类药物的抗病毒特性。

Current drug targets. Infectious disorders Pub Date : 2004-06-01 DOI: 10.2174/1568005043340920

Sara Richter, Cristina Parolin, Manlio Palumbo, Giorgio Palù

{"title":"Antiviral properties of quinolone-based drugs.","authors":"Sara Richter, Cristina Parolin, Manlio Palumbo, Giorgio Palù","doi":"10.2174/1568005043340920","DOIUrl":"https://doi.org/10.2174/1568005043340920","url":null,"abstract":"Quinolones represent an important class of broad-spectrum antibacterials, the main structural features of which are a 1,4 dihydro-4-oxo-quinolinyl moiety bearing an essential carboxyl group at position 3. Quinolones inhibit prokaryotic type II topoisomerases, namely DNA gyrase and, in a few cases, topoisomerase IV, through direct binding to the bacterial chromosome. Based on the hypothesis that these drugs could also bind to the viral nucleic acids or nucleoprotein-complexes, several quinolone derivatives were tested for their antiviral activity. Indeed, antibacterial fluoroquinolones were shown to be effective against vaccinia virus and papovaviruses; these preliminary results prompted the synthesis of modified quinolones to optimize antiviral action and improve selectivity index. The introduction of an aryl group at the piperazine moiety of the fluoroquinolone shifted the activity from antibacterial to antiviral, with a specific action against HIV. The antiviral activity seemed to be related to an inhibitory effect at the transcriptional level, and further evidence suggested a mechanism of action mediated by inhibition of Tat functions. Substitution of the fluorine at position 6 with an amine group to give aryl-piperazinyl-6-amino-quinolones improved the activity and selectivity against HIV-1: the most potent compound of this series was shown to inhibit virus replication through interference with Tat-TAR interaction. A comprehensive SAR investigation was performed based on additional chemical intervention to the quinolone template moiety, such as the introduction of nucleoside derivative functions. The information gained so far will be useful for future rational drug design aimed at developing new compounds with optimized antiviral activity.","PeriodicalId":84525,"journal":{"name":"Current drug targets. Infectious disorders","volume":"4 2","pages":"111-6"},"PeriodicalIF":0.0,"publicationDate":"2004-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568005043340920","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24552418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 69

Aminoglycoside nephrotoxicity. 氨基糖苷类肾毒性。

Current drug targets. Infectious disorders Pub Date : 2004-06-01 DOI: 10.2174/1568005043340858

F Rougier, D Claude, M Maurin, P Maire

{"title":"Aminoglycoside nephrotoxicity.","authors":"F Rougier, D Claude, M Maurin, P Maire","doi":"10.2174/1568005043340858","DOIUrl":"https://doi.org/10.2174/1568005043340858","url":null,"abstract":"The main constraints to the administration of aminoglycosides (AG) are risks of nephrotoxicity and ototoxicity, which can lead to renal and vestibular failure. AG accumulation in the kidney may be related to the dosing schedule. As a result, administration of larger doses on a less frequent basis may reduce the drug accumulation in the renal cortex. Many methods have been proposed to reduce AG nephrotoxicity. (1) Molecular modeling and analog synthesis could lead to intrinsically less toxic AG but this approach is time consuming and expensive. Protective approaches such as the co-administration of polyaspartic acid or defferoxamine appear to be very promising in clinical practice. (2) Population pharmacokinetic computer programs, used to control AG serum concentrations, are correct predictors of efficacy but the estimated concentrations in the second compartment are not reliable predictors of nephrotoxicity because they do not take into account non-linear processes such as the AG uptake in the renal cortex or the tubuloglomerular feedback. (3) Finally, modelling the AG nephrotoxicity with probabilistic approaches and/or with deterministic approaches seems to be very promising. These two approaches appear to be not competitive but very complementary in clinical practice. The probabilistic model can be used to predict nephrotoxicity at the beginning the treatment. The deterministic model can be used to simulate and control nephrotoxicity when it is already unfolding and the treatment must be given for a long period of time.","PeriodicalId":84525,"journal":{"name":"Current drug targets. Infectious disorders","volume":"4 2","pages":"153-62"},"PeriodicalIF":0.0,"publicationDate":"2004-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24552421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 20

Vaccine therapy for hepatitis B virus carrier. 乙型肝炎病毒携带者的疫苗治疗。

Current drug targets. Infectious disorders Pub Date : 2004-06-01 DOI: 10.2174/1568005043340885

Sk Md Fazle Akbar, Shinya Furukawa, Norio Horiike, Morikazu Onji

{"title":"Vaccine therapy for hepatitis B virus carrier.","authors":"Sk Md Fazle Akbar, Shinya Furukawa, Norio Horiike, Morikazu Onji","doi":"10.2174/1568005043340885","DOIUrl":"https://doi.org/10.2174/1568005043340885","url":null,"abstract":"Despite the presence of an effective prophylactic vaccine since 1982, more than 350 million people of the world are now chronically infected with hepatitis B virus (HBV). In one scenario, a considerable numbers of chronic HBV carrier would eventually develop serious complications like liver cirrhosis and hepatocellular carcinoma. In another, chronic HBV carriers would be permanent sources of HBV infection and transmit HBV to uninfected healthy individuals. Taken together, chronic HBV infection represents a major global public health problem, especially in the developing nations of the Asia and Africa, where most of the chronic HBV-carriers reside. Unfortunately, there is no good curative therapy approach for these patients. The prospect of treatment of chronic HBV infection by antiviral agents like type-1 interferons and lamivudine is not satisfactory due to their low efficacy, considerable side effects and high costs. Vaccine therapy, an immune therapy, has recently shown considerable optimism for treating patients with chronic HBV infection. In this review, we will first describe the pathogenesis of chronic HBV carrier state to provide scientific and ethical rationales of vaccine therapy in chronic HBV carriers. Next, we will summarize the information that has been compiled from ongoing clinical trials of vaccine therapy in chronic HBV carrier. Finally, we will discuss the mechanism of action of vaccine therapy in patients with chronic HBV infection and HBV transgenic mice, a murine model of chronic HBV carrier state. This information will be valuable for developing next generation therapeutic vaccines for the management of chronic HBV infection.","PeriodicalId":84525,"journal":{"name":"Current drug targets. Infectious disorders","volume":"4 2","pages":"93-101"},"PeriodicalIF":0.0,"publicationDate":"2004-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24551359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 22