Literature DB >> 25561178

A new antibiotic kills pathogens without detectable resistance.

Losee L Ling1, Tanja Schneider2, Aaron J Peoples1, Amy L Spoering1, Ina Engels2, Brian P Conlon3, Anna Mueller2, Till F Schäberle4, Dallas E Hughes1, Slava Epstein5, Michael Jones6, Linos Lazarides6, Victoria A Steadman6, Douglas R Cohen1, Cintia R Felix1, K Ashley Fetterman1, William P Millett1, Anthony G Nitti1, Ashley M Zullo1, Chao Chen3, Kim Lewis3.   

Abstract

Antibiotic resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis. Most antibiotics were produced by screening soil microorganisms, but this limited resource of cultivable bacteria was overmined by the 1960s. Synthetic approaches to produce antibiotics have been unable to replace this platform. Uncultured bacteria make up approximately 99% of all species in external environments, and are an untapped source of new antibiotics. We developed several methods to grow uncultured organisms by cultivation in situ or by using specific growth factors. Here we report a new antibiotic that we term teixobactin, discovered in a screen of uncultured bacteria. Teixobactin inhibits cell wall synthesis by binding to a highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid). We did not obtain any mutants of Staphylococcus aureus or Mycobacterium tuberculosis resistant to teixobactin. The properties of this compound suggest a path towards developing antibiotics that are likely to avoid development of resistance.

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Year:  2015        PMID: 25561178     DOI: 10.1038/nature14098

Source DB:  PubMed          Journal:  Nature        ISSN: 0028-0836            Impact factor:   49.962


  49 in total

1.  Antibiotics: Recover the lost art of drug discovery.

Authors:  Kim Lewis
Journal:  Nature       Date:  2012-05-23       Impact factor: 49.962

2.  An alternative bactericidal mechanism of action for lantibiotic peptides that target lipid II.

Authors:  Hester E Hasper; Naomi E Kramer; James L Smith; J D Hillman; Cherian Zachariah; Oscar P Kuipers; Ben de Kruijff; Eefjan Breukink
Journal:  Science       Date:  2006-09-15       Impact factor: 47.728

3.  Use of ichip for high-throughput in situ cultivation of "uncultivable" microbial species.

Authors:  D Nichols; N Cahoon; E M Trakhtenberg; L Pham; A Mehta; A Belanger; T Kanigan; K Lewis; S S Epstein
Journal:  Appl Environ Microbiol       Date:  2010-02-19       Impact factor: 4.792

4.  Antistaphylococcal activity of ceftobiprole, a new broad-spectrum cephalosporin.

Authors:  Tatiana Bogdanovich; Lois M Ednie; Stuart Shapiro; Peter C Appelbaum
Journal:  Antimicrob Agents Chemother       Date:  2005-10       Impact factor: 5.191

5.  D-Ala-D-Ala ligases from glycopeptide antibiotic-producing organisms are highly homologous to the enterococcal vancomycin-resistance ligases VanA and VanB.

Authors:  C G Marshall; G Broadhead; B K Leskiw; G D Wright
Journal:  Proc Natl Acad Sci U S A       Date:  1997-06-10       Impact factor: 11.205

Review 6.  Penicillin: the medicine with the greatest impact on therapeutic outcomes.

Authors:  Nelson Kardos; Arnold L Demain
Journal:  Appl Microbiol Biotechnol       Date:  2011-10-02       Impact factor: 4.813

Review 7.  Limitations of vancomycin in the management of resistant staphylococcal infections.

Authors:  Marin H Kollef
Journal:  Clin Infect Dis       Date:  2007-09-15       Impact factor: 9.079

8.  Relationship of MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant Staphylococcus aureus bacteremia.

Authors:  George Sakoulas; Pamela A Moise-Broder; Jerome Schentag; Alan Forrest; Robert C Moellering; George M Eliopoulos
Journal:  J Clin Microbiol       Date:  2004-06       Impact factor: 5.948

9.  Activated ClpP kills persisters and eradicates a chronic biofilm infection.

Authors:  B P Conlon; E S Nakayasu; L E Fleck; M D LaFleur; V M Isabella; K Coleman; S N Leonard; R D Smith; J N Adkins; K Lewis
Journal:  Nature       Date:  2013-11-13       Impact factor: 49.962

10.  Standard operating procedure for calculating genome-to-genome distances based on high-scoring segment pairs.

Authors:  Alexander F Auch; Hans-Peter Klenk; Markus Göker
Journal:  Stand Genomic Sci       Date:  2010-01-28
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  592 in total

1.  Laser MICROSAMPLING of soil microbial community.

Authors:  M V Gorlenko; E A Chutko; E S Churbanova; N V Minaev; K I Kachesov; L V Lysak; S A Evlashin; V S Cheptsov; A O Rybaltovskiy; V I Yusupov; V S Zhigarkov; G A Davydova; B N Chichkov; V N Bagratashvili
Journal:  J Biol Eng       Date:  2018-11-28       Impact factor: 4.355

Review 2.  Antimicrobial resistance: a global multifaceted phenomenon.

Authors:  Francesca Prestinaci; Patrizio Pezzotti; Annalisa Pantosti
Journal:  Pathog Glob Health       Date:  2015-09-07       Impact factor: 2.894

Review 3.  [New antibacterial agents on the market and in the pipeline].

Authors:  W V Kern
Journal:  Internist (Berl)       Date:  2015-11       Impact factor: 0.743

4.  Socially mediated induction and suppression of antibiosis during bacterial coexistence.

Authors:  Monica I Abrudan; Fokko Smakman; Ard Jan Grimbergen; Sanne Westhoff; Eric L Miller; Gilles P van Wezel; Daniel E Rozen
Journal:  Proc Natl Acad Sci U S A       Date:  2015-07-27       Impact factor: 11.205

5.  A chemocentric view of the natural product inventory.

Authors:  Christopher T Walsh
Journal:  Nat Chem Biol       Date:  2015-09       Impact factor: 15.040

Review 6.  Antibacterial drug discovery in the resistance era.

Authors:  Eric D Brown; Gerard D Wright
Journal:  Nature       Date:  2016-01-21       Impact factor: 49.962

7.  Synthetic cycle of the initiation module of a formylating nonribosomal peptide synthetase.

Authors:  Janice M Reimer; Martin N Aloise; Paul M Harrison; T Martin Schmeing
Journal:  Nature       Date:  2016-01-14       Impact factor: 49.962

8.  High-Throughput Single-Cell Cultivation on Microfluidic Streak Plates.

Authors:  Cheng-Ying Jiang; Libing Dong; Jian-Kang Zhao; Xiaofang Hu; Chaohua Shen; Yuxin Qiao; Xinyue Zhang; Yapei Wang; Rustem F Ismagilov; Shuang-Jiang Liu; Wenbin Du
Journal:  Appl Environ Microbiol       Date:  2016-02-05       Impact factor: 4.792

9.  Assembly and clustering of natural antibiotics guides target identification.

Authors:  Chad W Johnston; Michael A Skinnider; Chris A Dejong; Philip N Rees; Gregory M Chen; Chelsea G Walker; Shawn French; Eric D Brown; János Bérdy; Dennis Y Liu; Nathan A Magarvey
Journal:  Nat Chem Biol       Date:  2016-02-01       Impact factor: 15.040

10.  Efficacious Analogs of the Lantibiotic Mutacin 1140 against a Systemic Methicillin-Resistant Staphylococcus aureus Infection.

Authors:  Mengxin Geng; Akshaya Ravichandran; Jerome Escano; Leif Smith
Journal:  Antimicrob Agents Chemother       Date:  2018-11-26       Impact factor: 5.191

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