sign in sign up
<<
Home , Teixobactin

Sebastian Kaulitzki/Alamy NATURE REVIEWS REVIEWS NATURE mutants resistant teixobactin- to isolate were unable the authors |

DRUG DISCOVERY of novel compounds, authors the are apotentially untapped reservoir aremental bacteria uncultured and success. As up to 99%of environ synthetic approaches have had little resource is limited and alternative vable microorganisms, but this were discovered by screening culti resistance. foraction and not to select does seem has acompletely novel mechanism of new the teixobactin, which ofcolleagues report discovery the resistance crisis.Now, and Lewis to combatting current the antibiotic pipeline is one of main the hurdles compounds discovery drug inthe The paucity of novel antimicrobial A newdrugforresistant bugs Most use inclinical

ANTIBACTERIAL DRUGS

© 2015 Macmillan Publishers Limited. Allrights reserved - - in situ brane; grown can be then bacteria rounded by mem asemi-permeable in one of 96chambers that is sur isolating an cell individual bacterial This approachbacteria. involves to screenpreviously uncultured soil multichannel iChip the called device developed ahigh-throughput, III. This explains why teixobactin is teichoicwall acidprecursor lipid precursorgycan lipid IIand cell the synthesis by targeting peptido the antibioticthe inhibits Further experiments that revealed or with -resistant burden in bacterial inmiceinfected resulting inasubstantial reduction showed promising bacteria fective against most Gram-negative and tuberculosis, Clostridium difficile pathogens, including other drug-resistant Gram-positive teixobactin is apotent inhibitor of antibiotic class. thus represents acompletely new has aunique chemical scaffold and bial compound, teixobactin, termed analysis showed that antimicro the against Gram-positive the pathogen showed promising inhibitory activity provisionally named Gram-negativethe β-proteobacteria, that from of an species extract anew andfrom found bacteria 10,000soil crobial activity obtained of extracts naturalin their environment. nurients and growth factors present . pneumoniae. Streptococcus In addition to The authors examined antimi the , as they have as they access to the . Moreover, teixobactin S. aureus in vivo RESEARCH HIGHLIGHTS Eleftheria terrae Mycobacterium Mycobacterium . Structural . Structural but is inef activity, S. aureus , - - ­

- - - , of is which aprotein. The target that has two drug targets, the neither mutants, probably due to fact the unable to isolate teixobactin-resistant shields peptidoglycan. and have an outer membrane that lack teichoic as they bacteria, acids ineffective against Gram-negative resistance await discovered. to be with a low propensity for to select conclude that similar compounds candidates,drug and authors the fordiscovery identifying promising of value the of natural product species. mechanism for Gram-positive to atransferrable encode resistance intrinsically resistant, it is unlikely negative and species is therefore producer of teixobactin is aGram- exist innature is unclear, but as the resistance mechanisms already preclude antibiotic binding. Whether emergence of lipid variants that of antibiotics more readily than the that block binding the -encoding genes can evolve less likely for to select resistance as ing of lipids rather than is mechanisms ofantibioticresistance. FURTHER READING 10.1038/nature14098 detectable resistance. A newantibiotickillspathogenswithout ORIGINAL RESEARCHPAPER 371–387 (2013) antibiotic discovery. Microbiol. Chief Editor,Chief Importantly, authors the were This study is aproof-of-principle (

http://dx.doi.org/10.1038/nrmicro3429

VOLUME 14 13 , 42–51 (2015) | Lewis, K. Platforms for , 42–51(2015)|Lewis,K.Platformsfor Nature Microbiology Reviews This articleismodifiedfrom the Christina TobinChristina Kåhrström original in Nature Rev. DrugDiscov. Blair, J.M.A. (2015) Nature

|

Nature Rev. Nature Microbiol. FEBRUARY 2015 http://dx.doi.org/ Ling,L. et al. Nature Rev. Molecular Molecular et al -

12 .

, , )