Antibiotics-Basel最新文献

{"title":"In Vitro Activity of Cefaclor/Beta-Lactamases Inhibitors (Clavulanic Acid and Sulbactam) Combination Against Extended-Spectrum Beta-Lactamase Producing Uropathogenic <i>E. coli</i>.","authors":"Ali Atoom, Bayan Alzubi, Dana Barakat, Rana Abu-Gheyab, Dalia Ismail-Agha, Awatef Al-Kaabneh, Nawfal Numan","doi":"10.3390/antibiotics14060603","DOIUrl":"10.3390/antibiotics14060603","url":null,"abstract":"<p><p><b>Background:</b> Urinary tract infections (UTIs) caused by the multidrug resistance (MDR) phenotype termed extended-spectrum beta lactamase (ESBL)-producing <i>E. coli</i> is a significant and growing global health concern. In response to the rising prevalence, the novel Beta Lactam-Beta Lactamase inhibitor (BL/BLI) combinations have been introduced in recent years. While these agents have shown efficacy, their clinical utility is constrained by high cost, limited availability, and emerging resistance mechanisms. The rational of this study was to test the in vitro activity of a cost-effective alternative to currently available BL-BLI combinations against ESBL-producing <i>E. coli</i> isolated from urinary tract infections (UTIs). <b>Objective:</b> This study investigates the in vitro antimicrobial activity of cefaclor (CFC), both as monotherapy and in combination with the β-lactamase inhibitors clavulanic acid (CA) and sulbactam (SUL), against 52 ESBL-producing <i>E. coli</i> isolates derived from urine cultures of patients diagnosed with UTIs. <b>Methods:</b> The susceptibility ranges were measured by disk diffusion and minimal inhibitory concentration (MIC) methods. In addition, the Time kill assay and disk approximation method were performed to measure the synergistic and bactericidal activity of the approached combination. <b>Results:</b> The MIC50 and MIC90 for CFC were improved from more than 128 µg/mL to 8/4 µg/mL when CFC was combined with either CA or SUL. The triple combination format of CFC/CA/SUL showed MIC50 and MIC90 values at 8/4/4 µg/mL and 64/32/32 µg/mL, respectively. The recovered susceptibility percentages were 54%, 54%, and 58% for CFC/CA, CFC/SUL, and CFC/CA/SUL combinations, respectively. Disk approximation and time-kill assay results revealed synergy and bactericidal effects when CFC combined with CA or SUL for isolates that showed susceptibility restorations of CFC when coupled with CA or SUL by the disk diffusion and MIC method. <b>Conclusions:</b> This study proposes a cost-effective combination that could mitigate resistance development and offer a sparing option to last resort treatment choices including carbapenems. However, testing efficacy in a clinical setting is crucial.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Genetic Background and Culture Medium Only Marginally Affect the In Vitro Evolution of <i>Pseudomonas aeruginosa</i> Toward Colistin Resistance.","authors":"Matteo Cervoni, Antonio Maria Ferriero, Alessandra Lo Sciuto, Francesca Guidi, Naida Babić Jordamović, Silvano Piazza, Olivier Jousson, Alfonso Esposito, Francesco Imperi","doi":"10.3390/antibiotics14060601","DOIUrl":"10.3390/antibiotics14060601","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Colistin is a last-resort treatment for <i>Pseudomonas aeruginosa</i> multidrug-resistant infections, but resistance to it is emerging. While colistin resistance in <i>P. aeruginosa</i> is typically associated with chromosomal mutations inducing lipopolysaccharide (LPS) aminoarabinosylation, other mutations unrelated to LPS modifications have been proposed to influence the extent of colistin resistance. Here, we examined whether the genetic background and culture conditions affect the evolution of high-level colistin resistance in this bacterium. <b>Methods</b>: We performed in vitro evolution experiments in the presence or absence of increasing colistin concentrations with two phylogenetically distant reference strains in a standard laboratory medium and in two media mimicking <i>P. aeruginosa</i> growth during lung or systemic infections. Resistance-associated mutations were identified by comparative genomics, and the role of selected mutated genes was validated by allele replacement, deletion, or conditional mutagenesis. <b>Results</b>: Most colistin-resistant mutants carried mutations in genes belonging to four functional groups: two-component systems controlling LPS aminoarabinosylation (PmrAB, PhoPQ), LPS biosynthesis, the production of the polyamine norspermidine, and fatty acid metabolism. No mutation was exclusively and invariably associated with a specific strain or medium. We demonstrated that norspermidine is detrimental to the acquisition of colistin resistance upon PmrAB activation and that impaired fatty acid biosynthesis can promote colistin resistance, even if it increases susceptibility to other antibiotics. <b>Conclusions</b>: The evolution of colistin resistance in <i>P. aeruginosa</i> appeared to be only marginally affected by the genetic background and culture conditions. Notably, mutations in fatty acid biosynthetic genes represent a newly identified genetic determinant of <i>P. aeruginosa</i> colistin resistance, warranting further investigation in clinical isolates.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antifungal Activity of Selected Naphthoquinones and Their Synergistic Combination with Amphotericin B Against <i>Cryptococcus neoformans</i> H99.","authors":"Naira Sulany Oliveira de Sousa, Juan Diego Ribeiro de Almeida, Linnek Silva da Rocha, Izabela de Mesquita Bárcia Moreira, Flávia da Silva Fernandes, Ani Beatriz Jackisch Matsuura, Kátia Santana Cruz, Emersom Silva Lima, Érica Simplício de Souza, Hagen Frickmann, João Vicente Braga de Souza","doi":"10.3390/antibiotics14060602","DOIUrl":"10.3390/antibiotics14060602","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Cryptococcosis, caused by <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i> species complexes, remains a significant health concern, particularly among immunocompromised patients. The emergence of antifungal resistance and toxicity of conventional treatment underscore the urgent need for novel therapeutic approaches. Combination therapies represent a promising strategy to enhance efficacy and overcome resistance. This study investigated the antifungal activity of five naphthoquinones against nine isolates of <i>Cryptococcus</i> spp. and assessed their synergistic effects with amphotericin B (AmB). <b>Methods</b>: In this study, five selected naphthoquinones were evaluated for their antifungal activity against <i>Cryptococcus</i> spp. isolates using broth microdilution assays to determine minimum inhibitory concentrations (MICs), according to CLSI guidelines. The potential synergistic effect with AmB was assessed using checkerboard assays, with synergy interpreted based on the fractional inhibitory concentration index (FICI). Cytotoxicity was evaluated in MRC-5 human lung fibroblast cells using the MTT assay. <b>Results</b>: Among the compounds tested, 2-methoxynaphthalene-1,4-dione (2-MNQ) demonstrated antifungal activity, with MIC values ranging from 3.12 to 12.5 µg/mL. Checkerboard assays revealed a synergistic interaction between 2-MNQ and AmB, with a fractional inhibitory concentration index (FICI) of 0.27. The combination reduced the MIC of AmB by 4.17-fold. These findings highlight the potential of synthetic naphthoquinones, particularly 2-MNQ, as effective antifungal agents with synergistic properties when combined with AmB. The observed synergy suggests complementary mechanisms, including increased fungal membrane permeability and oxidative stress induction. <b>Conclusions</b>: This study highlights the potential of 2-MNQ and 2,3-DBNQ as antifungal candidates against <i>Cryptococcus</i> spp., with emphasis on the synergistic interaction observed between 2-MNQ and amphotericin B. The findings reinforce the importance of structural modifications in naphthoquinones to enhance antifungal activity and support the need for further preclinical studies investigating combination therapies aimed at improving treatment efficacy in patients with cryptococcosis.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibiotic Resistance Awareness in Kosovo: Insights from the WHO Antibiotic Resistance: Multi-Country Public Awareness Survey.","authors":"Flaka Pasha, Valon Krasniqi, Adelina Ismaili, Shaip Krasniqi, Elton Bahtiri, Hasime Qorraj Bytyqi, Valmira Kolshi Krasniqi, Blana Krasniqi","doi":"10.3390/antibiotics14060599","DOIUrl":"10.3390/antibiotics14060599","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Antimicrobial resistance (AMR) poses a critical global health threat, rendering common bacterial infections increasingly difficult to treat and placing considerable strain on healthcare systems. This study assesses public awareness, perceptions, and behaviors related to antibiotic use and AMR in Kosovo, a country with limited existing data on the topic. <b>Methods:</b> Using a cross-sectional survey design, 568 participants from diverse demographic backgrounds provided insights into their knowledge and practices concerning antibiotic use and antibiotic resistance. <b>Results:</b> The results revealed that although 75% of participants had heard of antibiotic resistance, only a limited proportion understood key terms. Knowledge of appropriate antibiotic use varied, with 67% of respondents correctly recognizing the need to complete a prescribed antibiotic course, while 29% believed it was acceptable to stop treatment once they felt better. Gender and educational level emerged as significant factors, with women and more educated individuals demonstrating greater awareness of proper antibiotic use and the risks of misuse. While 71% of respondents considered it unacceptable to use antibiotics prescribed to others, 41% believed it was acceptable to reuse previously effective antibiotics. Most participants (96%) reported obtaining antibiotics through prescriptions. Public awareness of AMR was generally high, but conceptual understanding remained limited, with misconceptions about the origins of resistance, incorrectly attributing it to the human body rather than bacteria. <b>Conclusions:</b> Targeted public health campaigns, guided by the One Health approach, integrating human, animal, and environmental health, are needed. A multifaceted strategy, including education, policy reforms, and international collaboration, is essential to mitigate AMR and preserve the efficacy of antibiotics for future generations.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics of Isavuconazole During Extracorporeal Membrane Oxygenation Support in Critically Ill Patients: A Case Series.","authors":"Laura Doménech-Moral, Sonia García-García, Alba Pau-Parra, Manuel Sosa, Adrian Puertas Sanjuan, Camilo Bonilla, Elisabeth Gallart, Laura Castellote, Patricia Faixó, Jessica Guevara, Albert Vilanova, María Martínez-Pla, Aldair Conto, Xavier Nuvials, Pilar Lalueza, Ricard Ferrer, Maria Queralt Gorgas, Jordi Riera","doi":"10.3390/antibiotics14060600","DOIUrl":"10.3390/antibiotics14060600","url":null,"abstract":"<p><strong>Background/objectives: </strong>Extracorporeal membrane oxygenation (ECMO) is increasingly used in critically ill patients, but may significantly alter the pharmacokinetics (PK) of antifungals. Data on plasma concentrations of Isavuconazole (IsaPlasm) in ECMO patients are limited. Our objective is to evaluate Isavuconazole exposure and variability in critically ill COVID-19 patients receiving ECMO.</p><p><strong>Methods: </strong>We conducted a pharmacokinetic analysis of Isavuconazole in critically ill patients receiving Veno-Venous ECMO for respiratory support. Plasma concentrations were measured using therapeutic drug monitoring (TDM) at multiple time points, including sampling before and after the membrane oxygenator. PK parameters-Area Under Curve (AUC_0-24), Minimum Plasma Concentration (Cmin), Elimination Half-Life (T_1/2), volume of distribution (Vd), and clearance (CL)-were estimated and compared with published data in non-ECMO populations.</p><p><strong>Results: </strong>Five patients were included. The median AUC_0-24 was 227.3 µg·h/mL (IQR 182.4-311.35), higher than reported in non-ECMO patients. The median Vd was 761 L (727-832), suggesting extensive peripheral distribution and potential drug sequestration in the ECMO circuit. CL was increased (1.6 L/h, IQR 1.5-3.4). Two patients with recently replaced ECMO circuits exhibited significant drug loss across the membrane. Obesity and hypoalbuminemia were identified as factors associated with altered drug exposure.</p><p><strong>Conclusions: </strong>Isavuconazole pharmacokinetics show marked variability in critically ill ECMO patients. Increased AUC and Vd, along with reduced clearance, highlight the need for individualized dosing.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ability of Linezolid to Combat <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i> Isolated from Polymicrobial Wound Infections.","authors":"Samar A Ahmed, Vy T Luu, Teresa C Oyono Nsuga, Steven E Burgos, Eugene Kreys, Jered Arquiette, Justin R Lenhard","doi":"10.3390/antibiotics14060597","DOIUrl":"10.3390/antibiotics14060597","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The optimal therapy for polymicrobial wound infections is poorly defined. We sought to characterize the ability of linezolid to combat mixed cultures of <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i>. <b>Methods</b>: The antistaphylococcal activity of linezolid was assessed in 24-h time-killing experiments that used <i>S. aureus</i> and <i>P. aeruginosa</i> isolated from polymicrobial wound infections. Clindamycin was also evaluated as a comparator. A Hill-type mathematical model was used to assess the maximum killing of <i>S. aureus</i> (E_max). The ability of linezolid to potentiate the activity of host defense peptides against <i>P. aeruginosa</i> was evaluated using LL-37. <b>Results</b>: In the presence of <i>P. aeruginosa</i>, the E_max of linezolid decreased in 5/9 co-culture experiments and increased in 4/9 co-culture experiments in comparison to linezolid against <i>S. aureus</i> alone. The potency of linezolid was not significantly impacted by the presence of <i>P. aeruginosa</i>. In comparison, the maximal <i>S. aureus</i> killing achieved by clindamycin decreased in eight out of nine experiments, and somewhat paradoxically, the potency increased in nine out of nine experiments. In the host defense peptide assay, the supratherapeutic linezolid concentration of 64 mg/L did not significantly enhance the killing of the LL-37 peptides (<i>p</i> ≥ 0.121), but the concentration of linezolid was significantly associated with the killing of one of three <i>P. aeruginosa</i> isolates (<i>p</i> = 0.005). <b>Conclusions</b>: <i>P. aeruginosa</i> had a minimal impact on the antistaphylococcal activity of linezolid in comparison to clindamycin. Linezolid did not exert a consistent ability to enhance the antipseudomonal activity of host defense peptides. These data may help inform antimicrobial selection during polymicrobial wound infections.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibiotic Resistance in Aquaculture: Challenges, Trends Analysis, and Alternative Approaches.","authors":"Elshafia Ali Hamid Mohammed, Béla Kovács, Ronald Kuunya, Eltayeb Omaima Awad Mustafa, Azza Siddig Hussien Abbo, Károly Pál","doi":"10.3390/antibiotics14060598","DOIUrl":"10.3390/antibiotics14060598","url":null,"abstract":"<p><p>Antibiotic resistance in aquaculture has emerged as a global crisis, representing a serious threat to the health of aquatic animals, environment, and human. The extensive use of antibiotics in aquaculture has led to rapid development of resistant bacterial strains, resulting in environmental contamination and the dissemination of resistant genes. Understanding of the research trends, key contributors, and thematic evolution of this field is essential for guiding future studies and policy interventions. The study aimed to conduct a bibliometric analysis of research on antibiotic resistance development in aquaculture, identifying key areas of research, leading contributors, emerging challenges, and alternative solutions. Data were extracted from the Web of Science (WoS) database covering the period from 2000 to 2025. A systematic search strategy was employed, utilizing terms including \"antibiotic resistance\" AND \"bacteria,\" AND \"aquaculture\". Relevant publications were extracted from the WoS using these keywords. R-tool was then used to analyze the obtained metadata including keywords, citation patterns, and co-authored country. The analysis revealed a remarkable increase in publications over the past 25 years, with key contributions from China, India, and the USA. The most significant articles focused on the presence of multidrug resistant bacteria in the aquatic environments and, antibiotic-resistant genes, and horizontal gene transfer. Probiotics are the alternative solution to overcome the antibiotic resistance and enhance aquaculture sustainability. Future research should focus on the interdisciplinary collaboration, novel antimicrobial alternatives, and global monitoring approaches.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Co-Existence of <i>mcr-1.1</i> and <i>mcr-3.5</i> in <i>Escherichia coli</i> Isolated from Clinical Samples in Thailand.","authors":"Panida Nobthai, Sirigade Ruekit, Dutsadee Peerapongpaisarn, Prawet Sukhchat, Brett E Swierczewski, Nattaya Ruamsap, Paphavee Lertsethtakarn","doi":"10.3390/antibiotics14060596","DOIUrl":"10.3390/antibiotics14060596","url":null,"abstract":"<p><p>The emergence of colistin resistance poses a significant threat to its efficacy as a last-line treatment against multidrug-resistant Gram-negative bacterial infections. In this study, 178 multi-drug resistant (MDR) <i>Escherichia coli</i> isolates collected from clinical samples at Queen Sirikit Naval Hospital, Chonburi, Thailand, were evaluated for colistin resistance. Of these, six were identified as <i>mcr</i> gene carriers, mediating colistin resistance. Specifically, <i>mcr-1</i> was detected in three <i>E. coli</i> isolates, <i>mcr-3</i> was detected in one <i>E. coli</i> isolate, and <i>mcr-1</i> and <i>mcr-3</i> were detected in two <i>E. coli</i> isolates, designated AMR-0220 and AMR-0361. Whole-genome sequencing and bioinformatics analysis revealed that AMR-0220 and AMR-0361 belonged to ST410 and ST617 lineages, respectively. Both isolates carried multiple plasmids, with <i>mcr-1.1</i> located on an IncX4-type plasmid that is closely related to previously reported <i>mcr-1.1</i>-carrying IncX4 plasmids. In contrast, <i>mcr-3.5</i> was identified on distinct plasmid backbones: an IncFIB-type plasmid in AMR-0220 and an IncFII-type plasmid in AMR-0361. Overall, our findings demonstrate that the <i>mcr</i> genes found in <i>E. coli</i> isolates in this region are located on different mobile genetic elements, indicating the potential for a widespread dissemination of colistin resistance among Gram-negative bacteria throughout Thailand's healthcare system.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epoxy-Functionalized Isatin Derivative: Synthesis, Computational Evaluation, and Antibacterial Analysis.","authors":"Deepanjali Shukla, Iqbal Azad, Mohd Arsh Khan, Ziaul Husain, Azhar Kamal, Sabahat Yasmeen Sheikh, Ibrahim Alotibi, Varish Ahmad, Firoj Hassan","doi":"10.3390/antibiotics14060595","DOIUrl":"10.3390/antibiotics14060595","url":null,"abstract":"<p><strong>Background/objectives: </strong>The current need for new antibacterial compounds that target non-classical pathways is highlighted by the emergence of multidrug-resistant <i>Klebsiella pneumoniae</i>. In the development of antibiotics, DNA adenine methyltransferase (Dam), a key regulator of bacterial gene expression and pathogenicity, is still underutilized. Epoxy-functionalized analogues of isatin derivatives have not been adequately investigated for their antibacterial activity, particularly as Dam inhibitors. In the pursuit of antimicrobial agents, this study synthesized an epoxy-functionalized isatin derivative (<b>L3</b>) using a one-pot reaction. The compound was characterized using FT-IR, ¹H-NMR, ¹³C-NMR, HR-MS, and UV-Vis spectroscopy.</p><p><strong>Methods: </strong><i>In silico</i> evaluation performed by using ADMETlab3 and SwissADME. While molecular docking studies were achieved by AutoDock and Vina to find <b>L3</b>'s interaction with potential antibacterial target (Dam protein in <i>K. pneumoniae</i>). In addition, the antibacterial potential of <b>L3</b> was evaluated using minimum inhibitory concentration (MIC) assays against <i>Bacillus cereus</i>, <i>Bacillus pumilus</i>, <i>Escherichia coli</i>, and <i>K. pneumoniae</i>.</p><p><strong>Results: </strong>Among these, <b>L3</b> exhibited potential inhibitory activity against <i>K. pneumoniae</i>, with a MIC value of 93.75 μg/mL. <i>In silico</i> evaluations confirmed <b>L3</b>'s favorable drug-like properties, including potential oral bioavailability, blood-brain barrier (BBB) permeability, and low plasma protein binding (PPB). The compound satisfied Lipinski's and other drug-likeness rules as well as getting a quantitative estimate of drug-likeness (QED) score of 0.52. Here, a homology model of Dam protein in <i>K. pneumoniae</i> was generated using the SWISS-MODEL server and validated using computational tools. Targeted docking analysis revealed that <b>L3</b> exhibited significant potential binding affinity against Dam protein, with binding energies of -6.4 kcal/mol and -4.85 kcal/mol, as determined by Vina and AutoDock, respectively. The associated inhibition constant was calculated as 280.35 µM. Further interaction analysis identified the formation of hydrogen bonds with TRP7 and PHE32, along with Van der Waals' interactions involving GLY9, ASP51, and ASP179.</p><p><strong>Conclusions: </strong>These findings highlight <b>L3</b> as a promising scaffold for antimicrobial drug development, particularly in targeting Dam protein in <i>K. pneumoniae</i>. Furthermore, the ADMET profiling and physicochemical properties of <b>L3</b> support its potential as a drug-like candidate.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144486989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibacterial and Synergistic Effects of <i>Terminalia citrina</i> Leaf Extracts Against Gastrointestinal Pathogens: Insights from Metabolomic Analysis.","authors":"Sze-Tieng Ang, Tak Hyun Kim, Matthew James Cheesman, Ian Edwin Cock","doi":"10.3390/antibiotics14060593","DOIUrl":"10.3390/antibiotics14060593","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Bacterial contamination leads to foodborne illnesses, and new antibiotics are required to combat these pathogens. Interest has increased in medicinal plants as targets for new antibiotics. <b>Methods</b>: This study evaluated the antibacterial activity of leaf extracts from <i>Terminalia citrina</i> (Gaertn.) Roxb. ex Fleming against four bacterial pathogens (including a methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) strain) using disc diffusion and liquid microdilution assays. The phytochemical composition of the extracts were determined using ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS). <b>Results</b>: Both the aqueous and methanol extracts demonstrated noteworthy antibacterial activity against <i>Bacillus cereus</i> (MICs of 468.8 µg/mL and 562.5 µg/mL, respectively). Additionally, the extracts were effective against MRSA (MICs = 625 µg/mL). Strong antibacterial effects were also observed against <i>S. aureus</i>, with MICs of 625 µg/mL (aqueous extract) and 833.3 µg/mL (methanol extract). Twelve combinations of extracts and conventional antibiotics were synergistic against <i>B. cereus</i> and <i>S. flexneri</i>. UPLC-MS analysis revealed two flavonoids, orientin 2″-O-gallate and astragalin, exclusive to the aqueous extract, whilst pinocembrin and gallic acid were only detected in the methanol extract. Both extracts contained vitexin 2″-O-p-coumarate, ellagic acid, orientin, rutin, chebulic acid, terminalin, and quercetin-3β-D-glucoside. Both extracts were determined to be nontoxic. <b>Conclusions</b>: The abundance and diversity of polyphenols in the extracts may contribute to their strong antibacterial properties. Further research is required to investigate the antibacterial effects of the individual extract compounds, including their effects when combined with conventional antibiotics, and the potential mechanisms of action against foodborne pathogens.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}