To describe the PHAGEinLYON Clinic programme, set up in 2022 to improve access to phage therapy in France using pharmaceutical-grade phages.
Methods
All phage therapy requests received during 2022 were collected prospectively, and reviewed retrospectively to analyse the decision and the patient care pathway (NCT05883995).
Results
Of 143 requests for phage therapy, the indication was confirmed at a multidisciplinary team meeting for 57 (40%) patients. Forty-four patients were infected with bacteria that could be targeted easily by phages in France. Finally, 33 patients were treated, including 26 at the study institution, through a compassionate access programme or in a clinical trial. The main indication were complex bone and joint infections, endovascular infection and lung infection. In order to manage these patients, 172 pharmaceutical phage cocktails targeting Staphylococcus aureus and/or Pseudomonas aeruginosa were prepared: 57 for local injection and 99 for intravenous injection. During follow-up, 18 (69%) patients showed a favourable clinical evolution, and six (23%) patients required subsequent phage therapy, either with the same phage with greater exposure, or with a different phage from elsewhere.
Conclusions
Implementation of the PHAGEinLYON Clinic programme in 2022 was associated with groundbreaking access to phage therapy in France.
{"title":"Access to phage therapy at Hospices Civils de Lyon in 2022: Implementation of the PHAGEinLYON Clinic programme","authors":"Tristan Ferry , Myrtille Le Bouar , Thomas Briot , Tiphaine Roussel-Gaillard , Thomas Perpoint , Sandrine Roux , Florence Ader , Florent Valour , Behrouz Kassai , Inesse Boussaha , Marietou Ndiaye , Fabien Craighero , Clément Javaux , Sébastien Lustig , Cécile Batailler","doi":"10.1016/j.ijantimicag.2024.107372","DOIUrl":"10.1016/j.ijantimicag.2024.107372","url":null,"abstract":"<div><h3>Objectives</h3><div>To describe the PHAGE<em>in</em>LYON <em>Clinic</em> programme, set up in 2022 to improve access to phage therapy in France using pharmaceutical-grade phages.</div></div><div><h3>Methods</h3><div>All phage therapy requests received during 2022 were collected prospectively, and reviewed retrospectively to analyse the decision and the patient care pathway (NCT05883995).</div></div><div><h3>Results</h3><div>Of 143 requests for phage therapy, the indication was confirmed at a multidisciplinary team meeting for 57 (40%) patients. Forty-four patients were infected with bacteria that could be targeted easily by phages in France. Finally, 33 patients were treated, including 26 at the study institution, through a compassionate access programme or in a clinical trial. The main indication were complex bone and joint infections, endovascular infection and lung infection. In order to manage these patients, 172 pharmaceutical phage cocktails targeting <em>Staphylococcus aureus</em> and/or <em>Pseudomonas aeruginosa</em> were prepared: 57 for local injection and 99 for intravenous injection. During follow-up, 18 (69%) patients showed a favourable clinical evolution, and six (23%) patients required subsequent phage therapy, either with the same phage with greater exposure, or with a different phage from elsewhere.</div></div><div><h3>Conclusions</h3><div>Implementation of the PHAGE<em>in</em>LYON <em>Clinic</em> programme in 2022 was associated with groundbreaking access to phage therapy in France.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107372"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567496","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}
Pub Date : 2024-12-01DOI: 10.1016/j.ijantimicag.2024.107379
Mete Ucdal , Emre Kara , Mustafa Berker , Aslı Pinar , Dolunay Gulmez , Sevtap Arikan-Akdagli , Ahmet Cağkan Inkaya , Gokhan Metan
{"title":"Monitoring of the cerebrospinal fluid voriconazole level in a patient with recurrent Candida meningitis after pituitary surgery","authors":"Mete Ucdal , Emre Kara , Mustafa Berker , Aslı Pinar , Dolunay Gulmez , Sevtap Arikan-Akdagli , Ahmet Cağkan Inkaya , Gokhan Metan","doi":"10.1016/j.ijantimicag.2024.107379","DOIUrl":"10.1016/j.ijantimicag.2024.107379","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107379"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Extended-spectrum β-lactamase-producing Escherichia coli remains a major cause of hospital-acquired bloodstream infections in countries with high antimicrobial stewardship compliance.
Methods
Isolates from bloodstream infections that occurred between 2010 and 2020 in a tertiary-level hospital in North-East Scotland soon after introduction of the ‘4C’ antimicrobial stewardship policy were analysed for phylogenetic structure, antimicrobial resistance, plasmid, and virulence gene carriage. Growth fitness was measured in kinetic assays. Non-metric-multidimensional-scaling was used to evaluate clonal relationships, antimicrobial resistance, and virulence profiles in early and later years after the 4C policy introduction. Clonal and fitness trends over the study period were determined by generalised additive modelling. The relationship between clonal type, antimicrobial resistance, and fitness was evaluated by linear regression.
Results
Three hierarchical phylogenetic clusters were identified, with the most dominant cluster (O25:H4/fimH30) including all, and nearly exclusively, Clade C ST131 isolates as well as minor non-ST131 sequence types. The prevalence of ST131 was largely stable over the study period. Resistance to aminoglycosides and aztreonam in ST131 was lower (P = 0.019 and P = 0.004, respectively) during later years (2016–2020) by 28% on average compared to early years soon after 4C policy implementation (2010–2014). Carriage of virulence factors involved in bacterial adaptation was higher in ST131 compared to non-ST131 but mostly stable in early vs. later years. Growth fitness of ST131 was lower than non-ST131 and declined steadily in later years (P < 0.0001).
Conclusions
Despite stable virulence factor carriage, population structure, and resistance to cephalosporins, we show increased susceptibility of ST131 to aminoglycosides and aztreonam and concurrent fitness decline years after the introduction of the 4C policy.
{"title":"Genomic and growth fitness study of extended-spectrum β-lactamase-producing Escherichia coli from bloodstream infections after introduction of a national 4C antimicrobial stewardship policy in Scotland","authors":"Istifanus Nkene , Susanth Alapati , Antonio Ribeiro , Ijeoma Okoliegbe , Sreedevi Unnikrishnan , Corinne Ironside , Becky Wilson , Karolin Hijazi","doi":"10.1016/j.ijantimicag.2024.107380","DOIUrl":"10.1016/j.ijantimicag.2024.107380","url":null,"abstract":"<div><h3>Background</h3><div>Extended-spectrum β-lactamase-producing <em>Escherichia coli</em> remains a major cause of hospital-acquired bloodstream infections in countries with high antimicrobial stewardship compliance.</div></div><div><h3>Methods</h3><div>Isolates from bloodstream infections that occurred between 2010 and 2020 in a tertiary-level hospital in North-East Scotland soon after introduction of the ‘4C’ antimicrobial stewardship policy were analysed for phylogenetic structure, antimicrobial resistance, plasmid, and virulence gene carriage. Growth fitness was measured in kinetic assays. Non-metric-multidimensional-scaling was used to evaluate clonal relationships, antimicrobial resistance, and virulence profiles in early and later years after the 4C policy introduction. Clonal and fitness trends over the study period were determined by generalised additive modelling. The relationship between clonal type, antimicrobial resistance, and fitness was evaluated by linear regression.</div></div><div><h3>Results</h3><div>Three hierarchical phylogenetic clusters were identified, with the most dominant cluster (O25:H4/<em>fimH30</em>) including all, and nearly exclusively, Clade C ST131 isolates as well as minor non-ST131 sequence types. The prevalence of ST131 was largely stable over the study period. Resistance to aminoglycosides and aztreonam in ST131 was lower (<em>P =</em> 0.019 and <em>P =</em> 0.004, respectively) during later years (2016–2020) by 28% on average compared to early years soon after 4C policy implementation (2010–2014). Carriage of virulence factors involved in bacterial adaptation was higher in ST131 compared to non-ST131 but mostly stable in early vs. later years. Growth fitness of ST131 was lower than non-ST131 and declined steadily in later years (<em>P <</em> 0.0001).</div></div><div><h3>Conclusions</h3><div>Despite stable virulence factor carriage, population structure, and resistance to cephalosporins, we show increased susceptibility of ST131 to aminoglycosides and aztreonam and concurrent fitness decline years after the introduction of the 4C policy.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107380"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619966","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}
Pub Date : 2024-12-01DOI: 10.1016/j.ijantimicag.2024.107385
{"title":"Reviewer Thank You List 2024","authors":"","doi":"10.1016/j.ijantimicag.2024.107385","DOIUrl":"10.1016/j.ijantimicag.2024.107385","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107385"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143143558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-23DOI: 10.1016/j.ijantimicag.2024.107391
{"title":"International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page","authors":"","doi":"10.1016/j.ijantimicag.2024.107391","DOIUrl":"10.1016/j.ijantimicag.2024.107391","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107391"},"PeriodicalIF":4.9,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142704056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-15DOI: 10.1016/j.ijantimicag.2024.107392
Yu-Wei Lin , S.Y. Amy Cheung
{"title":"Model-Informed Drug Development (MIDD) for Antimicrobials","authors":"Yu-Wei Lin , S.Y. Amy Cheung","doi":"10.1016/j.ijantimicag.2024.107392","DOIUrl":"10.1016/j.ijantimicag.2024.107392","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107392"},"PeriodicalIF":4.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-05DOI: 10.1016/j.ijantimicag.2024.107374
Mohan Ju , Min Hao , Dongfang Lin, Shuang Liu
Background
Cefiderocol is a new catecholamine-containing siderophore cephalosporin. It, however, remains unclear how cefiderocol modulates the immune response of the host.
Objectives
This study elucidated whether cefiderocol exerts immunoprotective effects in an in vitro experimental model induced with lipopolysaccharide (LPS).
Methods
Mouse macrophage RAW 264.7 cells were exposed to LPS (100 ng/mL) or LPS + cefiderocol (40 mg/L) to assess the immunomodulatory effect of cefiderocol in vitro. ELISA was performed on cell culture supernatants to estimate cytokine levels. Ferroptosis level was also quantified by detecting intracellular reactive oxygen species and iron levels through flow cytometry analysis. Malondialdehyde and glutathione (GSH) levels were estimated by ELISA. We conducted western blotting assay for evaluating key ferroptosis pathway proteins.
Results
Cefiderocol alleviated LPS-induced inflammation by reducing IL-6, TNF-α, and IL-1β production levels and enhancing the IL-10 production level. Further analysis to determine the underlying mechanism revealed that cefiderocol inhibited ferroptosis; this was confirmed by reduced reactive oxygen species, malondialdehyde, and Fe2+ ion levels; increased GSH levels; upregulated expression of solute carrier family 7 member 11, GSH peroxidase 4, nuclear factor erythroid 2-related factor 2, and ferroptosis suppressor protein 1; and downregulated expression of acyl-CoA synthetase long-chain family member 4.
Conclusions
Cefiderocol may play a key role in reducing inflammation by decreasing inflammatory cytokine release and suppressing ferroptosis.
{"title":"Cefiderocol has immunoregulative effects in LPS-induced vitro experimental model via inhibiting inflammation and ferroptosis","authors":"Mohan Ju , Min Hao , Dongfang Lin, Shuang Liu","doi":"10.1016/j.ijantimicag.2024.107374","DOIUrl":"10.1016/j.ijantimicag.2024.107374","url":null,"abstract":"<div><h3>Background</h3><div>Cefiderocol is a new catecholamine-containing siderophore cephalosporin. It, however, remains unclear how cefiderocol modulates the immune response of the host.</div></div><div><h3>Objectives</h3><div>This study elucidated whether cefiderocol exerts immunoprotective effects in an in vitro experimental model induced with lipopolysaccharide (LPS).</div></div><div><h3>Methods</h3><div>Mouse macrophage RAW 264.7 cells were exposed to LPS (100 ng/mL) or LPS + cefiderocol (40 mg/L) to assess the immunomodulatory effect of cefiderocol in vitro. ELISA was performed on cell culture supernatants to estimate cytokine levels. Ferroptosis level was also quantified by detecting intracellular reactive oxygen species and iron levels through flow cytometry analysis. Malondialdehyde and glutathione (GSH) levels were estimated by ELISA. We conducted western blotting assay for evaluating key ferroptosis pathway proteins.</div></div><div><h3>Results</h3><div>Cefiderocol alleviated LPS-induced inflammation by reducing IL-6, TNF-α, and IL-1β production levels and enhancing the IL-10 production level. Further analysis to determine the underlying mechanism revealed that cefiderocol inhibited ferroptosis; this was confirmed by reduced reactive oxygen species, malondialdehyde, and Fe<sup>2+</sup> ion levels; increased GSH levels; upregulated expression of solute carrier family 7 member 11, GSH peroxidase 4, nuclear factor erythroid 2-related factor 2, and ferroptosis suppressor protein 1; and downregulated expression of acyl-CoA synthetase long-chain family member 4.</div></div><div><h3>Conclusions</h3><div>Cefiderocol may play a key role in reducing inflammation by decreasing inflammatory cytokine release and suppressing ferroptosis.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107374"},"PeriodicalIF":4.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603820","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}
Pub Date : 2024-10-31DOI: 10.1016/j.ijantimicag.2024.107375
Hao Zhang , Jun Zeng , Tingting Zhu , Tao Lin , Turun Song
Background
Tuberculosis (TB) is a major and severe opportunistic infection among solid organ transplant recipients. Chemoprophylaxis is advised for those with latent tuberculosis infection. However, the effectiveness of an isoniazid (INH) prophylactic approach based on TB risk factors remains uncertain.
Methods
This study included all living-donor kidney transplant recipients between January 2016 and December 2022. The recipients were categorized into three groups: the risk group with INH (R-INH), the risk group without INH (R-NINH), and the non-risk group (NR), based on the presence of TB risk factors and INH usage. The R-INH group received a 6-month INH prophylactic regimen to prevent post-transplant TB infection. The incidence of active TB among the groups was assessed.
Results
A total of 1348 patients were divided into R-INH (n = 108), R-NINH (n = 371), and NR (n = 869). Forty-seven patients (3.49%) developed TB with an incidence rate of 16.0 per 1000 person-years. Compared to NR, the TB incidence in R-INH was not statistically different (hazard ratios, 0.55, 95% confidence interval, 0.07–4.21, P = 0.564), whereas it was significantly higher in R-NINH (hazard ratios, 5.04, 95% confidence interval, 2.64–9.62, P < 0.001). The median time from transplantation to TB was 19 months (interquartile range: 6–39), and 18 patients (38.3%) were diagnosed within 1 year of transplantation. Ninety-four patients (87.0%) completed INH prophylaxis, with adverse events including two cases of hepatotoxicity (1.85%) and one case of peripheral neuritis (0.93%).
Conclusions
A 6-month INH regimen based on TB risk factors is effective and well-tolerated for preventing post-transplant TB in kidney transplant recipients.
{"title":"Isoniazid prophylaxis based on tuberculosis risk factors in living kidney transplantation recipients: A retrospective cohort study","authors":"Hao Zhang , Jun Zeng , Tingting Zhu , Tao Lin , Turun Song","doi":"10.1016/j.ijantimicag.2024.107375","DOIUrl":"10.1016/j.ijantimicag.2024.107375","url":null,"abstract":"<div><h3>Background</h3><div>Tuberculosis (TB) is a major and severe opportunistic infection among solid organ transplant recipients. Chemoprophylaxis is advised for those with latent tuberculosis infection. However, the effectiveness of an isoniazid (INH) prophylactic approach based on TB risk factors remains uncertain.</div></div><div><h3>Methods</h3><div>This study included all living-donor kidney transplant recipients between January 2016 and December 2022. The recipients were categorized into three groups: the risk group with INH (R-INH), the risk group without INH (R-NINH), and the non-risk group (NR), based on the presence of TB risk factors and INH usage. The R-INH group received a 6-month INH prophylactic regimen to prevent post-transplant TB infection. The incidence of active TB among the groups was assessed.</div></div><div><h3>Results</h3><div>A total of 1348 patients were divided into R-INH (<em>n</em> = 108), R-NINH (<em>n</em> = 371), and NR (<em>n</em> = 869). Forty-seven patients (3.49%) developed TB with an incidence rate of 16.0 per 1000 person-years. Compared to NR, the TB incidence in R-INH was not statistically different (hazard ratios, 0.55, 95% confidence interval, 0.07–4.21, <em>P</em> = 0.564), whereas it was significantly higher in R-NINH (hazard ratios, 5.04, 95% confidence interval, 2.64–9.62, <em>P</em> < 0.001). The median time from transplantation to TB was 19 months (interquartile range: 6–39), and 18 patients (38.3%) were diagnosed within 1 year of transplantation. Ninety-four patients (87.0%) completed INH prophylaxis, with adverse events including two cases of hepatotoxicity (1.85%) and one case of peripheral neuritis (0.93%).</div></div><div><h3>Conclusions</h3><div>A 6-month INH regimen based on TB risk factors is effective and well-tolerated for preventing post-transplant TB in kidney transplant recipients.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107375"},"PeriodicalIF":4.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-31DOI: 10.1016/j.ijantimicag.2024.107371
Le Fu , Xu Zheng , Jiawen Luo , Yiyu Zhang , Xue Gao , Li Jin , Wenting Liu , Chaoqun Zhang , Dongyu Gao , Bocheng Xu , Qingru Jiang , Shuli Chou , Liang Luo
Objectives
Skin injuries and infections are an inevitable part of daily human life, particularly with chronic wounds, becoming an increasing socioeconomic burden. In treating skin infections and promoting wound healing, bioactive peptides may hold significant potential, particularly those possessing antimicrobial and anti-inflammatory properties. However, obtaining these peptides solely through traditional wet laboratory experiments is costly and time-consuming, and peptides identified by current computer-assisted predictive models largely lack validation of their effects via wet laboratory experiments. Consequently, this study aimed to integrate computer-assisted methods and traditional wet laboratory experiments to identify anti-inflammatory and antimicrobial peptides.
Methods
We developed a computer-assisted mining pipeline to screen potential peptides from the epitopes of the major histocompatibility complex class II.
Results
The peptide AIMP1 was identified, with the ability to physically damage Escherichia coli by increasing bacterial cell membrane permeability, and with the ability to inhibit inflammation by binding to endotoxin-lipopolysaccharide. Additionally, in an LPS-induced inflammation animal model, AIMP1 slightly increased levels of proinflammatory cytokines (TNF-α, IL-1β, and IL-6), and in a skin wound infection animal model, AIMP1 effectively accelerated healing, reduced levels of these pro-inflammatory cytokines, and showed no acute hepatotoxicity or nephrotoxicity.
Conclusions
In conclusion, this study not only developed a computer-assisted mining pipeline for identifying anti-inflammatory and antimicrobial peptides but also successfully pinpointed the peptide AIMP1, demonstrating its therapeutic potential for skin injury treatment.
{"title":"Machine learning accelerates the discovery of epitope-based dual-bioactive peptides against skin infections","authors":"Le Fu , Xu Zheng , Jiawen Luo , Yiyu Zhang , Xue Gao , Li Jin , Wenting Liu , Chaoqun Zhang , Dongyu Gao , Bocheng Xu , Qingru Jiang , Shuli Chou , Liang Luo","doi":"10.1016/j.ijantimicag.2024.107371","DOIUrl":"10.1016/j.ijantimicag.2024.107371","url":null,"abstract":"<div><h3>Objectives</h3><div>Skin injuries and infections are an inevitable part of daily human life, particularly with chronic wounds, becoming an increasing socioeconomic burden. In treating skin infections and promoting wound healing, bioactive peptides may hold significant potential, particularly those possessing antimicrobial and anti-inflammatory properties. However, obtaining these peptides solely through traditional wet laboratory experiments is costly and time-consuming, and peptides identified by current computer-assisted predictive models largely lack validation of their effects via wet laboratory experiments. Consequently, this study aimed to integrate computer-assisted methods and traditional wet laboratory experiments to identify anti-inflammatory and antimicrobial peptides.</div></div><div><h3>Methods</h3><div>We developed a computer-assisted mining pipeline to screen potential peptides from the epitopes of the major histocompatibility complex class II.</div></div><div><h3>Results</h3><div>The peptide AIMP1 was identified, with the ability to physically damage <em>Escherichia coli</em> by increasing bacterial cell membrane permeability, and with the ability to inhibit inflammation by binding to endotoxin-lipopolysaccharide. Additionally, in an LPS-induced inflammation animal model, AIMP1 slightly increased levels of proinflammatory cytokines (TNF-α, IL-1β, and IL-6), and in a skin wound infection animal model, AIMP1 effectively accelerated healing, reduced levels of these pro-inflammatory cytokines, and showed no acute hepatotoxicity or nephrotoxicity.</div></div><div><h3>Conclusions</h3><div>In conclusion, this study not only developed a computer-assisted mining pipeline for identifying anti-inflammatory and antimicrobial peptides but also successfully pinpointed the peptide AIMP1, demonstrating its therapeutic potential for skin injury treatment.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107371"},"PeriodicalIF":4.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564414","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}
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