A new antibiotic kills pathogens without detectable resistance

被引：1806

作者：

Ling, Losee L. ^{[1
]}

Schneider, Tanja ^{[2
,3
]}

Peoples, Aaron J. ^{[1
]}

Spoering, Amy L. ^{[1
]}

Engels, Ina ^{[2
,3
]}

Conlon, Brian P. ^{[4
]}

Mueller, Anna ^{[2
,3
]}

Schaeberle, Till F. ^{[3
,5
]}

Hughes, Dallas E. ^{[1
]}

Epstein, Slava ^{[6
]}

Jones, Michael ^{[7
]}

Lazarides, Linos ^{[7
]}

Steadman, Victoria A. ^{[7
]}

Cohen, Douglas R. ^{[1
]}

Felix, Cintia R. ^{[1
]}

Fetterman, K. Ashley ^{[1
]}

Millett, William P. ^{[1
]}

Nitti, Anthony G. ^{[1
]}

Zullo, Ashley M. ^{[1
]}

Chen, Chao ^{[4
]}

Lewis, Kim ^{[4
]}

机构：

[1] NovoBiot Pharmaceut, Cambridge, MA 02138 USA

[2] Univ Bonn, Immunol & Parasitol Pharmaceut Microbiol Sect, Inst Med Microbiol, D-53115 Bonn, Germany

[3] German Ctr Infect Res DZIF, D-53115 Bonn, Germany

[4] Northeastern Univ, Dept Biol, Antimicrobial Discovery Ctr, Boston, MA 02115 USA

[5] Univ Bonn, Inst Pharmaceut Biol, D-53115 Bonn, Germany

[6] Northeastern Univ, Dept Biol, Boston, MA 02115 USA

[7] Selcia, Ongar CM5 0GS, Essex, England

来源：

NATURE | 2015年 / 517卷 / 7535期

关键词：

CELL-WALL BIOSYNTHESIS; PRECURSOR LIPID II; STAPHYLOCOCCUS-AUREUS; STREPTOCOCCUS-PNEUMONIAE; PEPTIDOGLYCAN PRECURSOR; VANCOMYCIN-RESISTANCE; ENTEROCOCCUS-FAECIUM; ESCHERICHIA-COLI; IN-VITRO; DISCOVERY;

D O I：

10.1038/nature14098

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：455 / +

页数：18

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