Montserrat Mora-Ochomogo, Mitchell A Jeffs, Josephine L Liu, Christopher T Lohans
{"title":"β-内酰胺酶底物特异性和外膜通透性对β-内酰胺敏感菌的抗生素庇护作用的贡献。","authors":"Montserrat Mora-Ochomogo, Mitchell A Jeffs, Josephine L Liu, Christopher T Lohans","doi":"10.1039/d5cb00092k","DOIUrl":null,"url":null,"abstract":"<p><p>The use of β-lactam antibiotics is threatened by antibiotic resistant bacteria that produce β-lactamases. These enzymes not only protect the bacteria that produce them but also shelter other bacteria in the same environment that would otherwise be susceptible. While this phenomenon is of clinical significance, many of the factors that contribute to β-lactamase-mediated antibiotic sheltering have not been well-studied. We report the development of a luminescence assay to directly monitor the survival of β-lactam-susceptible bacteria in the presence of β-lactamase-producing bacteria and β-lactam antibiotics. This method provides a rapid and scalable means of quantifying antibiotic sheltering in mixed microbial populations. We applied this assay to investigate the contributions of several factors to sheltering, including the class of β-lactam, the substrate specificity of the β-lactamase, and the cell wall permeability of the β-lactamase-producing bacterium. Our results show that the extent of sheltering that occurs not only depends on the particular combination of β-lactam and β-lactamase, but is also greatly impacted by the ability of a β-lactamase to access its β-lactam substrates.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403027/pdf/","citationCount":"0","resultStr":"{\"title\":\"Contributions of β-lactamase substrate specificity and outer membrane permeability to the antibiotic sheltering of β-lactam-susceptible bacteria.\",\"authors\":\"Montserrat Mora-Ochomogo, Mitchell A Jeffs, Josephine L Liu, Christopher T Lohans\",\"doi\":\"10.1039/d5cb00092k\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The use of β-lactam antibiotics is threatened by antibiotic resistant bacteria that produce β-lactamases. These enzymes not only protect the bacteria that produce them but also shelter other bacteria in the same environment that would otherwise be susceptible. While this phenomenon is of clinical significance, many of the factors that contribute to β-lactamase-mediated antibiotic sheltering have not been well-studied. We report the development of a luminescence assay to directly monitor the survival of β-lactam-susceptible bacteria in the presence of β-lactamase-producing bacteria and β-lactam antibiotics. This method provides a rapid and scalable means of quantifying antibiotic sheltering in mixed microbial populations. We applied this assay to investigate the contributions of several factors to sheltering, including the class of β-lactam, the substrate specificity of the β-lactamase, and the cell wall permeability of the β-lactamase-producing bacterium. Our results show that the extent of sheltering that occurs not only depends on the particular combination of β-lactam and β-lactamase, but is also greatly impacted by the ability of a β-lactamase to access its β-lactam substrates.</p>\",\"PeriodicalId\":40691,\"journal\":{\"name\":\"RSC Chemical Biology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2025-08-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403027/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"RSC Chemical Biology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1039/d5cb00092k\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"RSC Chemical Biology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1039/d5cb00092k","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Contributions of β-lactamase substrate specificity and outer membrane permeability to the antibiotic sheltering of β-lactam-susceptible bacteria.
The use of β-lactam antibiotics is threatened by antibiotic resistant bacteria that produce β-lactamases. These enzymes not only protect the bacteria that produce them but also shelter other bacteria in the same environment that would otherwise be susceptible. While this phenomenon is of clinical significance, many of the factors that contribute to β-lactamase-mediated antibiotic sheltering have not been well-studied. We report the development of a luminescence assay to directly monitor the survival of β-lactam-susceptible bacteria in the presence of β-lactamase-producing bacteria and β-lactam antibiotics. This method provides a rapid and scalable means of quantifying antibiotic sheltering in mixed microbial populations. We applied this assay to investigate the contributions of several factors to sheltering, including the class of β-lactam, the substrate specificity of the β-lactamase, and the cell wall permeability of the β-lactamase-producing bacterium. Our results show that the extent of sheltering that occurs not only depends on the particular combination of β-lactam and β-lactamase, but is also greatly impacted by the ability of a β-lactamase to access its β-lactam substrates.