| RRC ID |
35584
|
| 著者 |
Bernier SP, Lebeaux D, DeFrancesco AS, Valomon A, Soubigou G, Coppée JY, Ghigo JM, Beloin C.
|
| タイトル |
Starvation, together with the SOS response, mediates high biofilm-specific tolerance to the fluoroquinolone ofloxacin.
|
| ジャーナル |
PLoS Genet
|
| Abstract |
High levels of antibiotic tolerance are a hallmark of bacterial biofilms. In contrast to well-characterized inherited antibiotic resistance, molecular mechanisms leading to reversible and transient antibiotic tolerance displayed by biofilm bacteria are still poorly understood. The physiological heterogeneity of biofilms influences the formation of transient specialized subpopulations that may be more tolerant to antibiotics. In this study, we used random transposon mutagenesis to identify biofilm-specific tolerant mutants normally exhibited by subpopulations located in specialized niches of heterogeneous biofilms. Using Escherichia coli as a model organism, we demonstrated, through identification of amino acid auxotroph mutants, that starved biofilms exhibited significantly greater tolerance towards fluoroquinolone ofloxacin than their planktonic counterparts. We demonstrated that the biofilm-associated tolerance to ofloxacin was fully dependent on a functional SOS response upon starvation to both amino acids and carbon source and partially dependent on the stringent response upon leucine starvation. However, the biofilm-specific ofloxacin increased tolerance did not involve any of the SOS-induced toxin-antitoxin systems previously associated with formation of highly tolerant persisters. We further demonstrated that ofloxacin tolerance was induced as a function of biofilm age, which was dependent on the SOS response. Our results therefore show that the SOS stress response induced in heterogeneous and nutrient-deprived biofilm microenvironments is a molecular mechanism leading to biofilm-specific high tolerance to the fluoroquinolone ofloxacin.
|
| 巻・号 |
9(1)
|
| ページ |
e1003144
|
| 公開日 |
2013-1-1
|
| DOI |
10.1371/journal.pgen.1003144
|
| PII |
PGENETICS-D-12-01226
|
| PMID |
23300476
|
| PMC |
PMC3536669
|
| MeSH |
Amino Acids / genetics
Anti-Bacterial Agents / pharmacology
Biofilms* / drug effects
Biofilms* / growth & development
DNA Transposable Elements / genetics*
Drug Resistance, Bacterial* / drug effects
Drug Resistance, Bacterial* / genetics
Drug Tolerance* / genetics
Escherichia coli* / genetics
Escherichia coli* / growth & development
Fluoroquinolones / pharmacology
Mutagenesis
Ofloxacin / pharmacology
Plankton / drug effects
Plankton / genetics
SOS Response, Genetics
Starvation
|
| IF |
5.175
|
| 引用数 |
113
|
|
WOS 分野
|
GENETICS & HEREDITY
|
| リソース情報 |
| 原核生物(大腸菌) |
JW0071-KC
JW2001-KC
JW2580-KC
JW3932-KC
JW3745-KC
JW0377-KC
JW2581-KC
JW1252-KC
JW2722-KC
JW2806-KC
JW3973-KC
JW2669-KC
JW2755-KC
JW0429-KC
JW2880-KC
JW0001-KC
JW2535-KC
JW3841-KC
JW0710-KC |
