Active Starvation Responses Mediate Antibiotic Tolerance in Biofilms and Nutrient-Limited Bacteria

被引：696

作者：

Dao Nguyen ^{[1
,2
]}

Joshi-Datar, Amruta ^{[3
,4
]}

Lepine, Francois ^{[5
]}

Bauerle, Elizabeth ^{[3
,4
]}

Olakanmi, Oyebode ^{[6
]}

Beer, Karlyn ^{[3
,4
]}

McKay, Geoffrey ^{[1
,2
]}

Siehnel, Richard ^{[3
,4
]}

Schafhauser, James ^{[1
,2
]}

Wang, Yun ^{[7
]}

Britigan, Bradley E. ^{[6
,8
]}

Singh, Pradeep K. ^{[3
,4
]}

机构：

[1] McGill Univ, Dept Med, Montreal, PQ H3G 1A4, Canada

[2] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3G 1A4, Canada

[3] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA

[4] Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA

[5] INRS Armand Frappier, Dept Microbiol, Laval, PQ H7V 1B7, Canada

[6] Univ Cincinnati, Dept Internal Med, Cincinnati, OH 45267 USA

[7] Northwestern Univ, Dept Civil & Environm Engn, Evanston, IL 60208 USA

[8] Vet Adm Med Ctr Cincinnati, Cincinnati, OH 45220 USA

来源：

SCIENCE | 2011年 / 334卷 / 6058期

关键词：

PSEUDOMONAS-AERUGINOSA; STRINGENT RESPONSE; INFECTION; DISEASE; DAMAGE; PQS;

D O I：

10.1126/science.1211037

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：

Bacteria become highly tolerant to antibiotics when nutrients are limited. The inactivity of antibiotic targets caused by starvation-induced growth arrest is thought to be a key mechanism producing tolerance. Here we show that the antibiotic tolerance of nutrient-limited and biofilm Pseudomonas aeruginosa is mediated by active responses to starvation, rather than by the passive effects of growth arrest. The protective mechanism is controlled by the starvation-signaling stringent response (SR), and our experiments link SR-mediated tolerance to reduced levels of oxidant stress in bacterial cells. Furthermore, inactivating this protective mechanism sensitized biofilms by several orders of magnitude to four different classes of antibiotics and markedly enhanced the efficacy of antibiotic treatment in experimental infections.

引用

页码：982 / 986

页数：6

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