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| Autor: | Cassandra, Kamischke, Junping, Fan, Julien, Bergeron, Hemantha D, Kulasekara, Zachary D, Dalebroux, Anika, Burrell, Justin M, Kollman, Samuel I, Miller |
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| Rok vydání: | 2018 |
| Předmět: |
Acinetobacter baumannii
Lipopolysaccharides glycerophospholipids Microbiology and Infectious Disease Escherichia coli Proteins Hydrolysis Cell Membrane Cryoelectron Microscopy Molecular Conformation Computational Biology Biological Transport Anti-Bacterial Agents ABC Transporter Adenosine Triphosphate Phenotype Mutagenesis Mutation DNA Transposable Elements Escherichia coli Other Genome Bacterial Bacterial Outer Membrane Proteins Research Article |
| Zdroj: | eLife |
| ISSN: | 2050-084X |
| Popis: | The outer membrane (OM) of Gram-negative bacteria serves as a selective permeability barrier that allows entry of essential nutrients while excluding toxic compounds, including antibiotics. The OM is asymmetric and contains an outer leaflet of lipopolysaccharides (LPS) or lipooligosaccharides (LOS) and an inner leaflet of glycerophospholipids (GPL). We screened Acinetobacter baumannii transposon mutants and identified a number of mutants with OM defects, including an ABC transporter system homologous to the Mla system in E. coli. We further show that this opportunistic, antibiotic-resistant pathogen uses this multicomponent protein complex and ATP hydrolysis at the inner membrane to promote GPL export to the OM. The broad conservation of the Mla system in Gram-negative bacteria suggests the system may play a conserved role in OM biogenesis. The importance of the Mla system to Acinetobacter baumannii OM integrity and antibiotic sensitivity suggests that its components may serve as new antimicrobial therapeutic targets. eLife digest Gram-negative bacteria are a large group of single-celled organisms that share a typical external envelope. This casing is formed of an inner and an outer membrane, which have different structures and properties. The outer membrane lets nutrients penetrate inside the cell, but blocks out other compounds, such as antibiotics. It is made of a complex assembly of molecules, including glycerolphospholipids (GPL) that are produced inside the cells. Very little is known about how this external shield is created and maintained. For example, it was still unclear how GPLs were exported through the inner membrane to the outer one. To investigate these questions, Kamischke et al. exposed a species of Gram-negative bacteria to a molecule that is normally blocked by the outer membrane. If the outer membrane is not working properly, the compound can cross it and the cell turns blue. Kamischke et al. then introduced genetic changes at random locations in the genomes of the bacteria. If colonies became blue, this meant that the mutations had happened in a gene essential for the outer membrane. Sequencing these blue bacteria revealed 58 genes involved in keeping the outer membrane working properly. Amongst them, four genes coded for a transport machine, the Mla system, which allowed GPLs to cross the inner membrane and reach the outer membrane. The experiments also showed that a working Mla system was required for bacteria to survive antibiotics. Certain dangerous Gram-negative bacteria are now resistant to many drugs, having evolved unique envelopes that keep antibiotics at bay. By learning more about the outer membrane, we may be able to create new treatments to bypass or to disable this shield, for example by targeting the Mla system. |
| Databáze: | OpenAIRE |
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