Antibiotics-Basel最新文献

{"title":"A Cross-Sectional Study Assessing Antibiotic Resistance Awareness Among University Students in Samborondón, Greater Guayaquil, Ecuador.","authors":"Norka Michelle Mora Pincay, José Luis Villegas, César Marcelo Larrea-Álvarez, Daniela Beatriz Briones Caiminagua, Lilibeth Torres-Elizalde, Miroslava Anna Šefcová, Marco Larrea-Álvarez","doi":"10.3390/antibiotics14050440","DOIUrl":"10.3390/antibiotics14050440","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Education on antibiotic use has the potential to positively shape the practices and perspectives of future professionals. Assessing awareness levels of antibiotic resistance among university students is, therefore, critical, as they represent a vital demographic capable of influencing public health outcomes, especially in low- and middle-income countries. <b>Methods:</b> This cross-sectional study employed the World Health Organization's Antibiotic Resistance: Multi-Country Public Awareness Survey, which examines demographics, antibiotic use, knowledge, perspectives, and sources of information. A total of 922 surveys were collected from students across various disciplines at two universities in Greater Guayaquil. <b>Results:</b> Most participants reported obtaining antibiotics through healthcare professionals, adhering to proper usage instructions, and purchasing them primarily from pharmacies. However, only 56% of the responses were correct, with many students incorrectly associating antibiotic use with conditions where they are typically ineffective. Despite these gaps, the students expressed positive attitudes toward proposed measures to address antibiotic resistance. While the participants demonstrated familiarity with terms related to antibiotic resistance and identified doctors and educators as their main sources of information, educational campaigns were not widely recognized as important. <b>Conclusions:</b> These findings evidence knowledge gaps among an essential group, suggesting the need for targeted health programs, preventive strategies, and educational initiatives to combat misinformation regarding antimicrobial resistance.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163681","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":"A Scoping Review Unveiling Antimicrobial Resistance Patterns in the Environment of Dairy Farms Across Asia.","authors":"Yuvaneswary Veloo, Syahidiah Syed Abu Thahir, Zunita Zakaria, Salina Abdul Rahman, Rozaihan Mansor, Sakshaleni Rajendiran","doi":"10.3390/antibiotics14050436","DOIUrl":"10.3390/antibiotics14050436","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) poses a significant \"One Health\" challenge in the farming industry attributed to antimicrobial misuse and overuse, affecting the health of humans, animals, and the environment. Recognizing the crucial role of the environment in facilitating the transmission of AMR is imperative for addressing this global health issue. Despite its urgency, there remains a notable gap in understanding resistance levels in the environment. This scoping review aims to consolidate and summarize available evidence of AMR prevalence and resistance genes in dairy farm settings. This study was conducted following the PRISMA Extension checklist to retrieve relevant studies conducted in Asian countries between 2013 and 2023. An electronic literature search involving PubMed, ScienceDirect, Embase, and Scopus resulted in a total of 1126 unique articles that were identified. After a full-text eligibility assessment, 39 studies were included in this review. The findings indicate that AMR studies in dairy farm environments have primarily focused on selective bacteria, especially <i>Escherichia coli</i> and other bacteria such as <i>Staphylococcus aureus</i>, <i>Klebsiella</i> spp., and <i>Salmonella</i> spp. Antimicrobial resistance patterns were reported across 24 studies involving 78 antimicrobials, which predominantly consisted of gentamicin (70.8%), ampicillin (58.3%), and tetracycline (58.3%). This review emphasizes the current state of AMR in the environmental aspects of dairy farms across Asia, highlighting significant gaps in regional coverage and bacterial species studied. It highlights the need for broader surveillance, integration with antimicrobial stewardship, and cross-sector collaboration to address AMR through a One Health approach.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163622","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":"Distribution, Antibiotic Resistance, and Virulence Factors of <i>Vibrio parahaemolyticus</i> in the Southern Coastal Waters of Republic of Korea.","authors":"Hyunwoo Zin, Intae Ham, Soonbum Shin, Hongsik Yu, Tae-Jin Choi, Kwangsoo Ha, Jong Soo Mok","doi":"10.3390/antibiotics14050435","DOIUrl":"10.3390/antibiotics14050435","url":null,"abstract":"<p><p><b>Background/Objectives:</b><i>Vibrio parahaemolyticus</i> is a marine bacterium and a major cause of food poisoning worldwide, primarily associated with gastric illnesses such as gastroenteritis. This study aimed to investigate the distribution, antibiotic resistance, and virulence genes of <i>V. parahaemolyticus</i> present in shellfish and seawater of the southern coast of Korea, a major shellfish harvesting area. <b>Methods:</b> Shellfish and seawater samples were collected monthly in 2023 from 24 coastal sites in Korea. <i>V. parahaemolyticus</i> was isolated and identified using the MPN method, biochemical tests, MALDI-TOF mass spectrometry, and 16S rRNA sequencing. Antimicrobial susceptibility was tested for 673 isolates using the Sensititre MIC system, and virulence genes (<i>tdh</i> and <i>trh</i>) were detected by PCR. <b>Results:</b><i>V. parahaemolyticus</i> had a detection rate of 18.2-58.3% in shellfish and 8.3-50% in seawater samples. Among the isolates, 97.9% and 97.3% were resistant to ampicillin and colistin, respectively, while 8.3% showed resistance to four or more antibiotics. The virulence genes <i>tdh</i> and <i>trh</i> were detected in 0.45% and 3.34% of shellfish samples and 1.23% and 4.46% of seawater samples, respectively. <b>Conclusions:</b> These findings will help implement appropriate precautionary measures to prevent potential human health risks arising from exposure to multidrug-resistant or pathogenic <i>V. parahaemolyticus</i>.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163693","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":"Anti-<i>Staphylococcus aureus</i> Activity and Structural Characterization of Rationally Designed Peptides.","authors":"Lorenza Artesani, Mariana Gallo, Laura Giovati, Francesca Maria Bisignano, Elena Ferrari, Lara M Castronovo, Stefania Conti, Francesco Santoro, Thelma A Pertinhez, Tecla Ciociola","doi":"10.3390/antibiotics14050437","DOIUrl":"10.3390/antibiotics14050437","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Microbial infections represent a significant threat to public health due to the emergence and spread of antimicrobial resistance. Adjunctive and alternative therapeutic strategies are explored to tackle this issue, including the use of natural or synthetic antimicrobial peptides. Previous research showed that antibody-derived peptides possess antimicrobial, antiviral, and immunomodulatory properties. This study aimed to characterize newly designed antibody-derived peptides and evaluate their effectiveness against representative strains of <i>Staphylococcus aureus</i>, including drug-resistant isolates. <b>Methods</b>: Colony-forming unit assays and confocal microscopy studies were performed to evaluate peptide activity against planktonic microbial cells. Cytotoxicity tests were performed on THP-1 human monocytic cells. Circular dichroism (CD) and nuclear magnetic resonance (NMR) were employed for the conformational characterization of peptides. <b>Results</b>: The half-maximal effective concentrations of the peptides against bacterial reference strains and drug-resistant isolates ranged from 0.17 to 18.05 µM, while cytotoxic effects were not observed against mammalian cells. A killing kinetics analysis and observation by confocal microscopy of the interaction between peptides and bacteria suggested a mechanism of action involving membrane perturbation. CD studies showed that all peptides predominantly exhibit a random coil arrangement in aqueous solution. NMR spectroscopy revealed that the most active peptide adopts a helical conformation in the presence of membrane mimetics. <b>Conclusions</b>: The structural characterization and evaluation of the newly designed peptides' antimicrobial activity may lead to the selection of a candidate to be further studied to develop an alternative treatment against microbial infections caused by drug-resistant strains.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163654","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":"Impact of Parenteral Ceftiofur on Developmental Dynamics of Early Life Fecal Microbiota and Antibiotic Resistome in Neonatal Lambs.","authors":"Mohamed Donia, Nasr-Eldin Aref, Mohamed Zeineldin, Ameer Megahed, Benjamin Blair, James Lowe, Brian Aldridge","doi":"10.3390/antibiotics14050434","DOIUrl":"10.3390/antibiotics14050434","url":null,"abstract":"<p><p><b>Background:</b> Early gut microbiome development is critical for neonatal health, and its dysbiosis may impact long-term animal productivity. This study examined the effects of parenteral Ceftiofur Crystalline Free Acid (CCFA) on the composition and diversity of the neonatal lamb fecal microbiome. The emergence of antimicrobial resistance genes associated with CCFA exposure was also investigated. <b>Results:</b> There were distinct microbial populations in the CCFA-treated lambs compared to the control group at each time point, with a highly significant decrease in alpha and beta diversity. The CCFA treatment showed a reduction in several key microbial taxa during nursing, but these differences were diminished by day 56. Unlike the control group, CCFA-treated lambs had core microbes potentially carrying multiple antibiotic resistance genes, including those for beta-lactam, fosfomycin, methicillin, and multidrug resistance. <b>Methods:</b> Twenty-four healthy neonatal lambs were randomly assigned to CCFA-treated (n = 12) and control (n = 12) groups. Fecal samples were collected on days 0, 7, 14, 28, and 56. Genomic DNA was extracted and sequenced using the Illumina MiSeq platform. Microbial composition was analyzed using the MG-RAST pipeline with the RefSeq database. <b>Conclusions:</b> Despite temporary reductions in critical bacterial populations during nursing, the early sheep fecal microbiome demonstrated resilience by repopulating after CCFA antibiotic disruption. While this highlights microbiota stability after short-course antibiotic exposure, the transient disturbance underscores potential risks to early gut health. Importantly, persistent CCFA resistance poses environmental dissemination risks, emphasizing the need for cautious antibiotic use in livestock to mitigate ecological impacts.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163305","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":"A One Health Approach Metagenomic Study on Antimicrobial Resistance Traits of Canine Saliva.","authors":"Adrienn Gréta Tóth, Darinka Lilla Tóth, Laura Remport, Imre Tóth, Tibor Németh, Attila Dubecz, Árpád V Patai, Zsombor Wagenhoffer, László Makrai, Norbert Solymosi","doi":"10.3390/antibiotics14050433","DOIUrl":"10.3390/antibiotics14050433","url":null,"abstract":"<p><p><b>Background:</b> According to the One Health concept, the physical proximity between pets and their owners facilitates the interspecies spread of bacteria including those that may harbor numerous antimicrobial resistance genes (ARGs). <b>Methods:</b> A shotgun sequencing metagenomic data-based bacteriome and resistome study of 1830 canine saliva samples was conducted considering the subsets of ARGs with higher public health risk, ESKAPE pathogen relatedness (<i>Enterococcus faecium</i>, <i>Staphylococcus aureus</i>, <i>Klebsiella pneumoniae</i>, <i>Acinetobacter baumannii</i>, <i>Pseudomonas aeruginosa</i> and <i>Enterobacter species</i>), and survey results on the physical and behavioral characteristics of the participating dogs. <b>Results:</b> A total of 318 ARG types achieved sufficiently high detection rates. These ARGs can affect 31 antibiotic drug classes through various resistance mechanisms. ARGs against tetracyclines, cephalosporins, and, interestingly, peptides appeared in the highest number of samples. Other Critically Important Antimicrobials (CIAs, WHO), such as aminoglycosides, fluoroquinolones, or macrolides, were among the drug classes most frequently affected by ARGs of higher public health risk and ESKAPE pathogen-related ARGs of higher public health risk. Several characteristics, including coat color, sterilization status, size, activity, or aggressiveness, were associated with statistically significant differences in ARG occurrence rates (<i>p</i> < 0.0500). <b>Conclusions:</b> Although the oral microbiome of pet owners is unknown, the One Health and public health implications of the close human-pet bonds and the factors potentially underlying the increase in salivary ARG numbers should be considered, particularly in light of the presence of ARGs affecting critically important drugs for human medicine.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163618","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 and Antibiofilm Activities of 2-Aminobenzoic Acid Derivatives Against a Clinical Ocular <i>Candida albicans</i> Isolate for Biomedical Applications.","authors":"Francesco Petrillo, Angela Maione, Marisa Spampinato, Lea Di Massa, Marco Guida, Armando Zarrelli, Emilia Galdiero, Luigi Longobardo","doi":"10.3390/antibiotics14050432","DOIUrl":"10.3390/antibiotics14050432","url":null,"abstract":"<p><p>Ocular fungal infections are slow-progressing conditions that primarily affect the cornea but can also involve the entire eyeball. <i>Candida albicans</i> is one of the most involved species. Both diagnosing and treating these infections require prompt and effective action. However, the currently available treatment options mainly rely on azoles and polyenes, which are known for their poor penetration into ocular tissue and associated toxicity. Moreover, conventional antifungals are usually ineffective when tested against biofilm-associated infections, mainly due to the metabolically inactive state of dormant cells embedded in the extracellular biofilm matrix. Here, analysis of the <i>in vitro</i> antifungal activity of four 2-aminobenzoic acid derivatives synthesized using a green method and their combination with Fluconazole (FLC) showed efficacy against the FLC-resistant clinical isolate of <i>C. albicans</i> under both planktonic and biofilm formation conditions. Results showed that compounds <b>1</b> and <b>2</b> exhibited the best antifungal activity in the checkerboard association test, presenting a synergistic effect towards antifungal action. The downregulation of <i>HWP</i>, <i>ERG11</i>, and <i>ASL3</i> genes during biofilm inhibition suggested a reduced capacity of the four compounds for hyphal growth and adhesion, as well as a decrease in pathogenicity due to the downregulation of some <i>SAP</i> genes. <i>In vitro</i> and <i>in vivo</i> toxicity profiles indicated that these compounds exhibited low toxicity, as well as the absence of genotoxic effects. Therefore, green-synthetized 2-aminobenzoic acid derivatives may have potential as antifungal agents for the inhibition of <i>C. albicans</i> growth and biofilm formation.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163717","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":"Repurposing of Furin Inhibitors to Reduce Pathogenic <i>E. coli</i>- and <i>Shigella flexneri</i>-Induced Cytotoxicity, Oxidative Stress and Inflammation in Mammalian Epithelial Cells.","authors":"Isabella Rumer, Lilla Tóth, Annelie Wohlert, András Adorján, Ákos Jerzsele, Roman W Lange, Torsten Steinmetzer, Erzsébet Gere-Pászti","doi":"10.3390/antibiotics14050431","DOIUrl":"10.3390/antibiotics14050431","url":null,"abstract":"<p><strong>Background/objectives: </strong>Enterobacteriaceae, including pathogenic <i>Shigella</i> (<i>S.</i>) <i>flexneri</i> and <i>Escherichia</i> (<i>E.</i>) <i>coli</i>, cause severe gastrointestinal infections through toxins like Shiga and Shiga-like toxins. Antibiotic use is often discouraged due to its potential to increase toxin effects or contribute to the development of resistance. The host protease furin is capable of activating several viral glycoproteins and bacterial toxins, thus enhancing pathogen infectivity.</p><p><strong>Methods: </strong>To assess the therapeutic potential of furin inhibitors, cultured epithelial cell models (IPEC-J2 and MDCK) were used. The effects of MI-1851 and MI-2415 were evaluated after short-term (2 h) and long-term (6 h) exposure to <i>S. flexneri</i>, enterohemorrhagic <i>E. coli</i> (EHEC), and enteropathogenic <i>E. coli</i> (EPEC). Cytotoxicity was determined using the CCK-8 assay, and the inflammatory response was assessed by measuring interleukin (IL)-6 and IL-8 levels. Additionally, extracellular hydrogen peroxide production was monitored in IPEC-J2 cells to evaluate the potential alterations in redox status.</p><p><strong>Results: </strong>Infections with EHEC, EPEC, and <i>S. flexneri</i> significantly reduced the viability of epithelial cells after 6 h of incubation. Furin inhibitors MI-1851 and MI-2415 decreased cytotoxicity and compensated for IL-6 and IL-8 overproduction in cells during infection with EHEC and <i>S. flexneri</i>, but not in cells exposed to EPEC. In addition, they alleviated oxidative stress, particularly during <i>S. flexneri</i> addition.</p><p><strong>Conclusions: </strong>The development of new antimicrobial drugs that act via alternative mechanisms and effectively manage life-threatening enterobacterial infections is of key importance. Targeting furin with inhibitors MI-1851 and MI-2415, thus blocking toxin activation, could prevent the development of antimicrobial resistance, reduce the need for antibiotics and enhance overall treatment outcomes.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163529","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 Peptides SmAP_α1-21 and SmAP_γ27-44 Designed from Different Loops of DefSm2-D Have Distinct Modes of Action.","authors":"Micaela Iturralde, Juan Pablo Bracho, Jessica A Valdivia-Pérez, Fanny Guzmán, Ismael Malbrán, Sabina María Maté, María Laura Fanani, Sandra Vairo Cavalli","doi":"10.3390/antibiotics14050430","DOIUrl":"10.3390/antibiotics14050430","url":null,"abstract":"<p><p><b>Background:</b> The use of antimicrobial peptides (AMPs) as biotechnological tools is an area of growing interest in the research that seeks to improve crop defense. SmAP_α1-21 and SmAP_γ27-44 were previously reported to inhibit <i>Fusarium graminearum</i>, permeabilize the plasma membrane and induce cytoplasmic disorganization. To exert its activity, SmAP_α1-21 initially enters through the basal and apical cells of <i>F. graminearum</i> conidia and then displays a general but non-homogeneous distribution in the cytoplasm of all conidial cells, in contrast. <b>Methods:</b> We analyzed, focusing on membrane interaction, the mode of action of SmAP_γ27-44, a peptide based on the γ-core of defensins DefSm2-D and DefSm3, and SmAP_α1-21, based on the α-core of DefSm2-D. Additionally, we compared the behavior of SmAP_α1-21 with that of SmAP3_α1-21 based on DefSm3 but with no activity against <i>F. graminearum</i>. <b>Results:</b> In this study, we showed that SmAP_γ27-44 enters the cells with discrete intracellular localization. Furthermore, both peptides disrupted the plasma membrane, but with different modes of action. When large unilamellar liposomes (LUVs) containing phosphatidic acid and ergosterol were used as a filamentous fungal plasma membrane model, SmAP_γ27-44 strongly induced aggregation concomitantly with the solubilization of the liposomes and showed the maximal insertion of its tryptophan moiety into the membrane's hydrophobic interior. In comparison, SmAP_α1-21 showed a high effect on the ζ potential of anionic vesicles, vesicle aggregation capacity after reaching a concentration threshold, and moderate transfer of tryptophan to the membrane. SmAP3_α1-21, on the other hand, showed poor superficial adsorption to liposomes. <b>Conclusions:</b> In view of our results, a cell penetration peptide-like effect was pictured for the γ-core defensin-derived peptide and a classical AMP action was observed for the α-core defensin-derived one.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144162581","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":"Genetically Modified Mesenchymal Stromal/Stem Cells as a Delivery Platform for SE-33, a Cathelicidin LL-37 Analogue: Preclinical Pharmacokinetics and Tissue Distribution in C57BL/6 Mice.","authors":"Vagif Ali Oglu Gasanov, Dmitry Alexandrovich Kashirskikh, Victoria Alexandrovna Khotina, Arthur Anatolievich Lee, Sofya Yurievna Nikitochkina, Daria Mikhailovna Kuzmina, Irina Vasilievna Mukhina, Ekaterina Andreevna Vorotelyak, Andrey Valentinovich Vasiliev","doi":"10.3390/antibiotics14050429","DOIUrl":"10.3390/antibiotics14050429","url":null,"abstract":"<p><strong>Background: </strong>The genetic modification of mesenchymal stromal/stem cells (MSCs) to express antimicrobial peptides may provide a promising strategy for developing advanced cell-based therapies for bacterial infections, including those caused or complicated by antibiotic-resistant bacteria. We have previously demonstrated that genetically modified Wharton's jelly-derived MSCs expressing an antimicrobial peptide SE-33 (WJ-MSC-SE33) effectively reduce bacterial load, inflammation, and mortality in a mouse model of <i>Staphylococcus aureus</i>-induced pneumonia compared with native WJ-MSCs. The present study aimed to evaluate the pharmacokinetics and tissue distribution of the SE-33 peptide expressed by WJ-MSC-SE33 following administration to animals.</p><p><strong>Methods: </strong>WJ-MSC-SE33 were administered to C57BL/6 mice at therapeutic and excess doses. The biodistribution and pharmacokinetics of the SE-33 peptide were analyzed in serum, lungs, liver, and spleen using chromatographic methods after single and repeated administrations.</p><p><strong>Results: </strong>The SE-33 peptide exhibited dose-dependent pharmacokinetics. The highest levels of SE-33 peptide were detected in the liver and lungs, with persistence in tissues for up to 48 h at medium and high doses of administered WJ-MSC-SE33. A repeated administration of WJ-MSC-SE33 increased SE-33 levels in target organs.</p><p><strong>Conclusions: </strong>The SE-33 peptide expressed by genetically modified WJ-MSCs demonstrated predictable pharmacokinetics and effective biodistribution. These findings, together with the previously established safety profile of WJ-MSC-SE33, support its potential as a promising cell-based therapy for bacterial infections, particularly those associated with antibiotic resistance.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163250","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}