{"title":"离子载体打破了鲍曼不动杆菌的多重耐药。","authors":"David M P De Oliveira, Mark J Walker","doi":"10.15698/mic2022.03.772","DOIUrl":null,"url":null,"abstract":"<p><p>Within intensive care units, multi-drug resistant <i>Acinetobacter baumannii</i> outbreaks are a frequent cause of ventilator-associated pneumonia. During the on-going COVID-19 pandemic, patients who receive ventilator support experience a 2-fold increased risk of mortality when they contract a secondary <i>A. baumannii</i> pulmonary infection. In our recent paper (De Oliveira <i>et al.</i> (2022), Mbio, doi: 10.1128/mbio.03517-21), we demonstrate that the 8-hydroxquinoline ionophore, PBT2 breaks the resistance of <i>A. baumannii</i> to tetracycline class antibiotics. <i>In vitro</i>, the combination of PBT2 and zinc with either tetracycline, doxycycline, or tigecycline was shown to be bactericidal against multi-drug-resistant <i>A. baumannii</i>, and any resistance that did arise imposed a fitness cost. Using a murine model of pulmonary infection, treatment with PBT2 in combination with tetracycline or tigecycline proved efficacious against multidrug-resistant <i>A. baumannii</i>. These findings suggest that PBT2 may find utility as a resistance breaker to rescue the efficacy of tetracycline-class antibiotics commonly employed to treat multi-drug resistant <i>A. baumannii</i> infections.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":null,"pages":null},"PeriodicalIF":4.1000,"publicationDate":"2022-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8890622/pdf/","citationCount":"1","resultStr":"{\"title\":\"An ionophore breaks the multi-drug-resistance of <i>Acinetobacter baumannii</i>.\",\"authors\":\"David M P De Oliveira, Mark J Walker\",\"doi\":\"10.15698/mic2022.03.772\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Within intensive care units, multi-drug resistant <i>Acinetobacter baumannii</i> outbreaks are a frequent cause of ventilator-associated pneumonia. During the on-going COVID-19 pandemic, patients who receive ventilator support experience a 2-fold increased risk of mortality when they contract a secondary <i>A. baumannii</i> pulmonary infection. In our recent paper (De Oliveira <i>et al.</i> (2022), Mbio, doi: 10.1128/mbio.03517-21), we demonstrate that the 8-hydroxquinoline ionophore, PBT2 breaks the resistance of <i>A. baumannii</i> to tetracycline class antibiotics. <i>In vitro</i>, the combination of PBT2 and zinc with either tetracycline, doxycycline, or tigecycline was shown to be bactericidal against multi-drug-resistant <i>A. baumannii</i>, and any resistance that did arise imposed a fitness cost. Using a murine model of pulmonary infection, treatment with PBT2 in combination with tetracycline or tigecycline proved efficacious against multidrug-resistant <i>A. baumannii</i>. These findings suggest that PBT2 may find utility as a resistance breaker to rescue the efficacy of tetracycline-class antibiotics commonly employed to treat multi-drug resistant <i>A. baumannii</i> infections.</p>\",\"PeriodicalId\":18397,\"journal\":{\"name\":\"Microbial Cell\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2022-03-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8890622/pdf/\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Microbial Cell\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.15698/mic2022.03.772\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microbial Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.15698/mic2022.03.772","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 1
摘要
在重症监护病房,多重耐药鲍曼不动杆菌暴发是呼吸机相关性肺炎的常见原因。在持续的COVID-19大流行期间,接受呼吸机支持的患者在感染继发性鲍曼不动杆菌肺部感染时死亡风险增加了两倍。在我们最近的论文(De Oliveira et al. (2022), Mbio, doi: 10.1128/ Mbio .03517-21)中,我们证明了8-羟基喹啉离子载体PBT2可以打破鲍曼不动杆菌对四环素类抗生素的耐药性。在体外实验中,PBT2和锌与四环素、多西环素或替加环素的组合被证明对多重耐药鲍曼不动杆菌具有杀菌作用,并且任何耐药性的产生都施加了适应度成本。通过小鼠肺部感染模型,PBT2联合四环素或替加环素治疗对多重耐药鲍曼不动杆菌有效。这些发现表明,PBT2可以作为一种耐药性破环剂,挽救通常用于治疗多重耐药鲍曼不动杆菌感染的四环素类抗生素的疗效。
An ionophore breaks the multi-drug-resistance of Acinetobacter baumannii.
Within intensive care units, multi-drug resistant Acinetobacter baumannii outbreaks are a frequent cause of ventilator-associated pneumonia. During the on-going COVID-19 pandemic, patients who receive ventilator support experience a 2-fold increased risk of mortality when they contract a secondary A. baumannii pulmonary infection. In our recent paper (De Oliveira et al. (2022), Mbio, doi: 10.1128/mbio.03517-21), we demonstrate that the 8-hydroxquinoline ionophore, PBT2 breaks the resistance of A. baumannii to tetracycline class antibiotics. In vitro, the combination of PBT2 and zinc with either tetracycline, doxycycline, or tigecycline was shown to be bactericidal against multi-drug-resistant A. baumannii, and any resistance that did arise imposed a fitness cost. Using a murine model of pulmonary infection, treatment with PBT2 in combination with tetracycline or tigecycline proved efficacious against multidrug-resistant A. baumannii. These findings suggest that PBT2 may find utility as a resistance breaker to rescue the efficacy of tetracycline-class antibiotics commonly employed to treat multi-drug resistant A. baumannii infections.