Antibiotics最新文献

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An Institutional Febrile Neutropenia Protocol Improved the Antibacterial Treatment and Encouraged the Development of a Computerized Clinical Decision Support System 机构发热性中性粒细胞减少症治疗方案改进了抗菌治疗并促进了计算机化临床决策支持系统的开发
Antibiotics Pub Date : 2024-09-02 DOI: 10.3390/antibiotics13090832
Zahit Taş, Gökhan Metan, Gülçin Telli Dizman, Eren Yavuz, Ömer Dizdar, Yahya Büyükaşık, Ömrüm Uzun, Murat Akova
{"title":"An Institutional Febrile Neutropenia Protocol Improved the Antibacterial Treatment and Encouraged the Development of a Computerized Clinical Decision Support System","authors":"Zahit Taş, Gökhan Metan, Gülçin Telli Dizman, Eren Yavuz, Ömer Dizdar, Yahya Büyükaşık, Ömrüm Uzun, Murat Akova","doi":"10.3390/antibiotics13090832","DOIUrl":"https://doi.org/10.3390/antibiotics13090832","url":null,"abstract":"We investigated the influence of a local guideline on the quality of febrile neutropenia (FN) management and the applicability of a computerized decision support system (CDSS) using real-life data. The study included 227 FN patients between April 2016 and January 2019. The primary outcome measure was the achievement of a 20% increase in the rate of appropriate empirical treatment of FN in bacteremic patients. The compatibility of the CDSS (the development of which was completed in November 2021) with local protocols was tested using standard patient scenarios and empirical antibiotic recommendations for bacteremic FN patients. In total, 91 patients were evaluated before (P1: between April 2016 and May 2017) and 136 after (P2: between May 2017 and January 2019) the guideline’s release (May 2017). The demographic characteristics were similar. Appropriate empirical antibacterial treatment was achieved in 58.3% of P1 and 88.1% of P2 patients (p = 0.006). The need for escalation of antibacterial treatment was significantly lower in P2 (49.5% vs. 35.3%; p = 0.03). In P2, the performance of the CDSS and consulting physicians was similar (CDSS 88.8% vs. physician 88.83%; p = 1) regarding appropriate empirical antibacterial treatment. The introduction of the local guideline improved the appropriateness of initial empirical treatment and reduced escalation rates in FN patients. The high rate of compliance of the CDSS with the local guideline-based decisions in P2 highlights the usefulness of the CDSS for these patients.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"181 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196172","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: 0
Whole-Genome Sequencing Reveals Temporal Trends in Antibiotic Resistance Genes in Escherichia coli Causing Pediatric Urinary Tract Infections in Central Vietnam 全基因组测序揭示引起越南中部小儿尿路感染的大肠埃希菌耐抗生素基因的时间趋势
Antibiotics Pub Date : 2024-09-02 DOI: 10.3390/antibiotics13090830
Huyen Thanh Thi Le, Trang Thu Hoang, Ngoc Anh Thi Nguyen, Sang Ngoc Nguyen, Ung Dinh Nguyen, Cuong Xuan Hoang, Nam S. Vo, Duc Quang Le, Son Hoang Nguyen, Minh Duc Cao, Tho Huu Ho
{"title":"Whole-Genome Sequencing Reveals Temporal Trends in Antibiotic Resistance Genes in Escherichia coli Causing Pediatric Urinary Tract Infections in Central Vietnam","authors":"Huyen Thanh Thi Le, Trang Thu Hoang, Ngoc Anh Thi Nguyen, Sang Ngoc Nguyen, Ung Dinh Nguyen, Cuong Xuan Hoang, Nam S. Vo, Duc Quang Le, Son Hoang Nguyen, Minh Duc Cao, Tho Huu Ho","doi":"10.3390/antibiotics13090830","DOIUrl":"https://doi.org/10.3390/antibiotics13090830","url":null,"abstract":"(1) Background: Pediatric urinary tract infections (UTIs) pose significant challenges due to drug-resistant Escherichia coli (E. coli) strains. This study utilizes whole-genome sequencing to analyze temporal trends in antibiotic resistance genes (ARGs) in clinical E. coli isolates from pediatric UTI cases in central Vietnam. (2) Methods: We conducted whole-genome sequencing on 71 E. coli isolates collected from pediatric UTI patients between 2018 and 2020. ARGs were identified, and their prevalence over time was analyzed. Statistical tests were used to correlate ARG presence with antibiotic resistance. (3) Results: Of the 47 E. coli isolates with complete data, 40 distinct ARGs were identified, with a median of 10 resistance genes per isolate. A significant increase in the total number of ARGs per isolate was observed over time, from an average of 8.88 before June 2019 to 11.63 after. Notably, the prevalence of the aadA2 gene (aminoglycoside resistance) rose from 0% to 26.7%, and that of the blaNDM-5 gene (beta-lactam and carbapenem resistance) increased from 0% to 23.3%. Key correlations include blaEC with cephalosporin resistance, blaNDM-5 with carbapenem resistance, and sul2 with sulfamethoxazole/trimethoprim resistance. (4) Conclusions: Whole-genome sequencing reveals complex and evolving antibiotic resistance patterns in pediatric E. coli UTIs in central Vietnam, with a marked increase in ARG prevalence over time. Continuous surveillance and targeted treatments are essential to address these trends. Understanding genetic foundations is crucial for effective intervention strategies.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196167","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: 0
Innovative Strategies in Drug Repurposing to Tackle Intracellular Bacterial Pathogens 应对细胞内细菌病原体的药物再利用创新战略
Antibiotics Pub Date : 2024-09-02 DOI: 10.3390/antibiotics13090834
Blanca Lorente-Torres, Jesús Llano-Verdeja, Pablo Castañera, Helena Á. Ferrero, Sergio Fernández-Martínez, Farzaneh Javadimarand, Luis M. Mateos, Michal Letek, Álvaro Mourenza
{"title":"Innovative Strategies in Drug Repurposing to Tackle Intracellular Bacterial Pathogens","authors":"Blanca Lorente-Torres, Jesús Llano-Verdeja, Pablo Castañera, Helena Á. Ferrero, Sergio Fernández-Martínez, Farzaneh Javadimarand, Luis M. Mateos, Michal Letek, Álvaro Mourenza","doi":"10.3390/antibiotics13090834","DOIUrl":"https://doi.org/10.3390/antibiotics13090834","url":null,"abstract":"Intracellular bacterial pathogens pose significant public health challenges due to their ability to evade immune defenses and conventional antibiotics. Drug repurposing has recently been explored as a strategy to discover new therapeutic uses for established drugs to combat these infections. Utilizing high-throughput screening, bioinformatics, and systems biology, several existing drugs have been identified with potential efficacy against intracellular bacteria. For instance, neuroleptic agents like thioridazine and antipsychotic drugs such as chlorpromazine have shown effectiveness against Staphylococcus aureus and Listeria monocytogenes. Furthermore, anticancer drugs including tamoxifen and imatinib have been repurposed to induce autophagy and inhibit bacterial growth within host cells. Statins and anti-inflammatory drugs have also demonstrated the ability to enhance host immune responses against Mycobacterium tuberculosis. The review highlights the complex mechanisms these pathogens use to resist conventional treatments, showcases successful examples of drug repurposing, and discusses the methodologies used to identify and validate these drugs. Overall, drug repurposing offers a promising approach for developing new treatments for bacterial infections, addressing the urgent need for effective antimicrobial therapies.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"169 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196208","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: 0
Correction: Abd El-Fattah et al. Immobilization of ZnO-TiO2 Nanocomposite into Polyimidazolium Amphiphilic Chitosan Film, Targeting Improving Its Antimicrobial and Antibiofilm Applications. Antibiotics 2023, 12, 1110 更正:Abd El-Fattah et al. 将 ZnO-TiO2 纳米复合材料固定到聚咪唑两亲壳聚糖薄膜中,旨在改善其抗菌和抗生物膜应用。抗生素 2023,12,1110
Antibiotics Pub Date : 2024-09-02 DOI: 10.3390/antibiotics13090836
Wesam Abd El-Fattah, Mohammad Y. Alfaifi, Jafar Alkabli, Heba A. Ramadan, Ali A. Shati, Serag Eldin I. Elbehairi, Reda F. M. Elshaarawy, Islam Kamal, Moustafa M. Saleh
{"title":"Correction: Abd El-Fattah et al. Immobilization of ZnO-TiO2 Nanocomposite into Polyimidazolium Amphiphilic Chitosan Film, Targeting Improving Its Antimicrobial and Antibiofilm Applications. Antibiotics 2023, 12, 1110","authors":"Wesam Abd El-Fattah, Mohammad Y. Alfaifi, Jafar Alkabli, Heba A. Ramadan, Ali A. Shati, Serag Eldin I. Elbehairi, Reda F. M. Elshaarawy, Islam Kamal, Moustafa M. Saleh","doi":"10.3390/antibiotics13090836","DOIUrl":"https://doi.org/10.3390/antibiotics13090836","url":null,"abstract":"In the original publication [...]","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196210","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: 0
A Retrospective Analysis of Intravenous Push versus Extended Infusion Meropenem in Critically Ill Patients 重症患者静脉推注与延长输注美罗培南的回顾性分析
Antibiotics Pub Date : 2024-09-02 DOI: 10.3390/antibiotics13090835
Emory G. Johnson, Kayla Maki Ortiz, David T. Adams, Satwinder Kaur, Andrew C. Faust, Hui Yang, Carlos A. Alvarez, Ronald G. Hall
{"title":"A Retrospective Analysis of Intravenous Push versus Extended Infusion Meropenem in Critically Ill Patients","authors":"Emory G. Johnson, Kayla Maki Ortiz, David T. Adams, Satwinder Kaur, Andrew C. Faust, Hui Yang, Carlos A. Alvarez, Ronald G. Hall","doi":"10.3390/antibiotics13090835","DOIUrl":"https://doi.org/10.3390/antibiotics13090835","url":null,"abstract":"Meropenem is a broad-spectrum antibiotic used for the treatment of multi-drug-resistant infections. Due to its pharmacokinetic profile, meropenem’s activity is optimized by maintaining a specific time the serum concentration remains above the minimum inhibitory concentration (MIC) via extended infusion (EI), continuous infusion, or intermittent infusion dosing strategies. The available literature varies regarding the superiority of these dosing strategies. This study’s primary objective was to determine the difference in time to clinical stabilization between intravenous push (IVP) and EI administration. We performed a retrospective pilot cohort study of 100 critically ill patients who received meropenem by IVP (n = 50) or EI (n = 50) during their intensive care unit (ICU) admission. There was no statistically significant difference in the overall achievement of clinical stabilization between IVP and EI (48% vs. 44%, p = 0.17). However, the median time to clinical stability was shorter for the EI group (20.4 vs. 66.2 h, p = 0.01). EI administration was associated with shorter hospital (13 vs. 17 days; p = 0.05) and ICU (6 vs. 9 days; p = 0.02) lengths of stay. Although we did not find a statistically significant difference in the overall time to clinical stabilization, the results of this pilot study suggest that EI administration may produce quicker clinical resolutions than IVP.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196169","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: 0
Trends in Antimicrobial Usage on Swiss Pig Farms from 2018 to 2021: Based on an Electronic Treatment Journal 2018 至 2021 年瑞士养猪场抗菌剂使用趋势:基于电子治疗期刊
Antibiotics Pub Date : 2024-09-02 DOI: 10.3390/antibiotics13090831
Ramona Wissmann, Dolf Kümmerlen, Thomas Echtermann
{"title":"Trends in Antimicrobial Usage on Swiss Pig Farms from 2018 to 2021: Based on an Electronic Treatment Journal","authors":"Ramona Wissmann, Dolf Kümmerlen, Thomas Echtermann","doi":"10.3390/antibiotics13090831","DOIUrl":"https://doi.org/10.3390/antibiotics13090831","url":null,"abstract":"(1) Background: The aim of this retrospective observational study was to observe the trends in antimicrobial usage (AMU) from 2018 to 2021 in Swiss pigs based on an electronic treatment journal used nationwide by farmers. Thus, for the first time, standardized, longitudinal comparisons of AMU between the years could be analyzed, as well as the influence of targeted interventions, on farms with higher consumption. (2) Methods: The data was evaluated by different indicators, such as the amount of active ingredient in kilograms, treatment days per farm (ATI) and treatment incidence (TI) based either on animal-defined daily doses (TIADD) or used daily doses (TIUDD). Calculations were performed across the following five age categories: suckling piglets, weaners, fattening pigs, and gestating and lactating sows, and the proportions of antimicrobial classes were evaluated for each age category. (3) Results: The highest amount of the active ingredient was administered to the group of fattening pigs, while the suckling piglets received the lowest amount of the active ingredient. In 2021, there was a significant decrease in active ingredient consumption per pig, but a significant increase in ATI, TIADD and TIUDD compared to 2018. The largest proportion of AMU was attributed to penicillins each year, followed by sulfonamides and tetracyclines. The “Highest Priority Critically Important Antimicrobials” represented a proportion of overall usage, declining from 5.2% in 2018 to 3.1% in 2021, while polypeptides were the most used class of critical antimicrobials. Interventions on high-usage farms showed that some farms decreased their AMU in the following year while others did not. (4) Conclusions: This study reveals a decrease in the overall usage measured in kilograms per pig of antimicrobials in Swiss pigs between 2019 and 2021 through the monitoring of AMU, but, at the same time, there was an increase in treatment days or incidence per farm. Critical antimicrobials can be reduced regardless of the indicator. The significance and quality of interventions should be investigated in future studies.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196171","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: 0
Assessing the Influence of Urine pH on the Efficacy of Ciprofloxacin and Fosfomycin in Immunocompetent and Immunocompromised Murine Models of Escherichia coli and Klebsiella pneumoniae Infection in the Lower Urinary Tract 评估尿液 pH 值对环丙沙星和磷霉素在免疫功能正常和免疫功能低下小鼠下尿路大肠埃希菌和肺炎克雷伯菌感染模型中药效的影响
Antibiotics Pub Date : 2024-09-01 DOI: 10.3390/antibiotics13090827
Soraya Herrera-Espejo, Marta Carretero-Ledesma, Manuel Anselmo Bahamonde-García, Elisa Cordero, Jerónimo Pachón, María Eugenia Pachón-Ibáñez
{"title":"Assessing the Influence of Urine pH on the Efficacy of Ciprofloxacin and Fosfomycin in Immunocompetent and Immunocompromised Murine Models of Escherichia coli and Klebsiella pneumoniae Infection in the Lower Urinary Tract","authors":"Soraya Herrera-Espejo, Marta Carretero-Ledesma, Manuel Anselmo Bahamonde-García, Elisa Cordero, Jerónimo Pachón, María Eugenia Pachón-Ibáñez","doi":"10.3390/antibiotics13090827","DOIUrl":"https://doi.org/10.3390/antibiotics13090827","url":null,"abstract":"In vitro studies have suggested that acidic pH may reduce and increase the efficacy of ciprofloxacin and fosfomycin, respectively, when used to treat Escherichia coli and Klebsiella pneumoniae infections. We assessed the effects of acidic, neutral, and alkaline urine pH on the efficacy of optimized ciprofloxacin and fosfomycin dosages in UTI murine model of E. coli and K. pneumoniae. Immunocompetent and immunocompromised mice with adjusted urine pH were inoculated with E. coli and K. pneumoniae strains, and the efficacy was assessed based on the bacterial concentrations in tissues and fluids at 72 h, with respect to untreated controls. At acidic urine pH, both antimicrobials were effective, achieving similar reductions in E. coli concentrations in the kidneys in immunocompetent and immunocompromised mice and in K. pneumoniae in immunocompetent mice. At a neutral urine pH, both therapies reduced the presence of E. coli in the kidneys of immunocompetent mice. However, in immunocompromised mice, antimicrobials were ineffective at treating E. coli infection in the kidneys at a neutral urine pH and showed reduced efficacy against K. pneumoniae at both acidic and neutral urine pH. The results showed no correlation between urine pH and antimicrobial efficacy, suggesting that the reduced effectiveness is associated with the animals’ immunocompetence status.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196211","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: 0
Sublethal Sodium Hypochlorite Exposure: Impact on Resistance-Nodulation-Cell Division Efflux Pump Overexpression and Cross-Resistance to Imipenem 亚致死次氯酸钠暴露:对抗性-结节-细胞分裂外排泵过表达和亚胺培南交叉抗性的影响
Antibiotics Pub Date : 2024-09-01 DOI: 10.3390/antibiotics13090828
Ji-Hyun Nam, Jung Sik Yoo
{"title":"Sublethal Sodium Hypochlorite Exposure: Impact on Resistance-Nodulation-Cell Division Efflux Pump Overexpression and Cross-Resistance to Imipenem","authors":"Ji-Hyun Nam, Jung Sik Yoo","doi":"10.3390/antibiotics13090828","DOIUrl":"https://doi.org/10.3390/antibiotics13090828","url":null,"abstract":"Sodium hypochlorite (NaOCl) is widely used in public healthcare facilities; this exposure can result in the development of bacterial tolerance to disinfectants, which has known links to antibiotic cross-resistance. However, the mechanism through which cross-resistance to antibiotics and disinfectants develops remains ambiguous. Therefore, this study aimed to examine the phenotypic and transcriptomic changes caused by disinfectant exposure in Gram-negative bacteria and determine the cause of cross-resistance to antibiotics. The results demonstrated that the misuse of disinfectants plays an important role in the emergence of disinfectant resistance and in the increase in antibiotic resistance. Antibiotic resistance may occur from the exposure of Gram-negative bacteria to subminimal inhibitory concentrations (MICs) of NaOCl. Ten passages of Gram-negative bacteria in increasingly higher subMICs of the NaOCl disinfectant were sufficient to increase the MIC to >2500 µg/mL NaOCl, particularly in K. pneumoniae and P. aeruginosa. To determine the development of cross-resistance to antibiotics due to NaOCl exposure, the MICs for each antibiotic before and after the exposure of each strain to sublethal concentrations of NaOCl were compared. After overnight incubation with a sublethal concentration of NaOCl, a statistically significant increase in MIC was only observed for imipenem (p < 0.01). An investigation of the mechanism of cross-resistance by means of transcriptome analysis revealed that 1250 µg/mL of NaOCl-adapted K. pneumoniae and P. aeruginosa strains increased resistance to imipenem due to the increased expression of resistance-nodulation-cell division (RND) efflux pumps, such as AcrAB-TolC and MexAB/XY-OprM. Therefore, we suggest that exposure to NaOCl can influence the expression of RND efflux pump genes, contributing to imipenem cross-resistance.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196212","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: 0
Diamine Fungal Inducers of Secondary Metabolism: 1,3-Diaminopropane and Spermidine Trigger Enzymes Involved in β-Alanine and Pantothenic Acid Biosynthesis, Precursors of Phosphopantetheine in the Activation of Multidomain Enzymes 次生代谢的二胺真菌诱导物:1,3-二氨基丙烷和精胺触发参与β-丙氨酸和泛酸生物合成的酶,激活多域酶的磷泛硫乙氨酸前体
Antibiotics Pub Date : 2024-09-01 DOI: 10.3390/antibiotics13090826
Juan Francisco Martín, Paloma Liras
{"title":"Diamine Fungal Inducers of Secondary Metabolism: 1,3-Diaminopropane and Spermidine Trigger Enzymes Involved in β-Alanine and Pantothenic Acid Biosynthesis, Precursors of Phosphopantetheine in the Activation of Multidomain Enzymes","authors":"Juan Francisco Martín, Paloma Liras","doi":"10.3390/antibiotics13090826","DOIUrl":"https://doi.org/10.3390/antibiotics13090826","url":null,"abstract":"The biosynthesis of antibiotics and other secondary metabolites (also named special metabolites) is regulated by multiple regulatory networks and cascades that act by binding transcriptional factors to the promoter regions of different biosynthetic gene clusters. The binding affinity of transcriptional factors is frequently modulated by their interaction with specific ligand molecules. In the last decades, it was found that the biosynthesis of penicillin is induced by two different molecules, 1,3-diaminopropane and spermidine, but not by putrescine (1,4-diaminobutane) or spermine. 1,3-diaminopropane and spermidine induce the expression of penicillin biosynthetic genes in Penicillium chrysogenum. Proteomic studies clearly identified two different proteins that respond to the addition to cultures of these inducers and are involved in β-alanine and pantothenic acid biosynthesis. These compounds are intermediates in the biosynthesis of phosphopantetheine that is required for the activation of non-ribosomal peptide synthetases, polyketide synthases, and fatty acid synthases. These large-size multidomain enzymes are inactive in the “apo” form and are activated by covalent addition of the phosphopantetheine prosthetic group by phosphopantetheinyl transferases. Both 1,3-diaminopropane and spermidine have a similar effect on the biosynthesis of cephalosporin by Acremonium chrysogenum and lovastatin by Aspergillus terreus, suggesting that this is a common regulatory mechanism in the biosynthesis of bioactive secondary metabolites/natural products.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196209","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: 0
Combinatory Effect of Nitroxoline and Gentamicin in the Control of Uropathogenic Enterococci Infections 硝唑嘧啶和庆大霉素在控制尿路致病性肠球菌感染中的联合作用
Antibiotics Pub Date : 2024-09-01 DOI: 10.3390/antibiotics13090829
Davorka Repac Antić, Bruno Kovač, Marko Kolenc, Irena Brčić Karačonji, Ivana Gobin, Mirna Petković Didović
{"title":"Combinatory Effect of Nitroxoline and Gentamicin in the Control of Uropathogenic Enterococci Infections","authors":"Davorka Repac Antić, Bruno Kovač, Marko Kolenc, Irena Brčić Karačonji, Ivana Gobin, Mirna Petković Didović","doi":"10.3390/antibiotics13090829","DOIUrl":"https://doi.org/10.3390/antibiotics13090829","url":null,"abstract":"Enterococcus faecalis, responsible for a majority of human and nosocomial enterococcal infections, is intrinsically resistant to aminoglycoside antibiotics (such as gentamicin, GEN), which must be used in a combined therapy to be effective. Nitroxoline (NTX) is an old antibiotic, underused for decades, but rediscovered now in an era of growing antibiotic resistance. In this in vitro study, the types of interactions between NTX and GEN on 29 E. faecalis strains were analyzed with an aim to find synergistic antimicrobial and antiadhesion combinations. Transmission electron microscopy (TEM) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to analyze changes in cell morphology and bacterial proteome after monotreatments and combined treatments. The results showed the synergistic effect for six combinations on eight strains, including the ATCC29212, and an additive effect for most strains. Combinations causing a complete inhibition of adhesion were established. Cell membrane integrity was affected by NTX, while combined NTX/GEN treatment caused dramatic changes in cell morphology. Upregulation of the expression of many proteins was established, with some emerging only after combined treatment. The results strongly imply that NTX has the potential for use in combined therapy with GEN against enterococci and it could further provide a substantial contribution to an ongoing fight against antimicrobial resistance and nosocomial infections.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196213","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: 0
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