scholarly journals Dual autogenous control of the multiple antibiotic resistance phenotype in Escherichia coli

2014 ◽  
Author(s):  
Guillermo Rodrigo ◽  
Djordje Bajic ◽  
Ignacio Elola ◽  
Juan F Poyatos

Bacteria can defend against diverse antibiotics by mounting a multiple antibiotic resistance (mar) phenotype. The resistance is linked to a chromosomal locus that encodes an activator and a repressor regulating their own expression. Here, we investigated how this dual autogenous control determines the dynamics of the response. We found that the regulatory architecture provides a mechanism to enable rapid induction, generate pulses of activation, and increase the range of sensing. The response is also graded and homogeneous across the population. Moreover, the interaction of a third regulator with the core module fine tunes the previous features, while limiting the cross-talk with metabolic signals. A minimal model accurately anticipates these properties, and emphasizes how specific attributes of the circuit components constrain the appearance of other potential behaviors associated to the regulatory design. Our results integrate both molecular and circuit-level characteristics to fully elucidate the dynamic emergence of the mar phenotype.

Author(s):  
Jianli Wang ◽  
Wenjian Ma ◽  
Yu Fang ◽  
Hao Liang ◽  
Huiting Yang ◽  
...  

Gram-negative bacteria are intrinsically resistant to antibiotics due to the presence of the cell envelope, but mechanisms are still not fully understood. In this study, a series of mutants that lack one or more major components associated with the cell envelope were constructed from Escherichia coli K-12 W3110. WJW02 can only synthesize Kdo 2 -lipid A which lacks the core oligosaccharide portion of lipopolysaccharide. WJW04, WJW07 and WJW08 were constructed from WJW02 by deleting the gene clusters relevant to the biosynthesis of exopolysaccharide, flagella and fimbria, respectively. WJW09, WJW010 and WJW011 cells cannot synthesize exopolysaccharide, flagella and fimbria, respectively. Comparing to the wild type W3110, mutants WJW02, WJW04, WJW07 and WJW08 cells showed decreased resistance to more than 10 different antibacterial drugs, but not the mutants WJW09, WJW010 and WJW011. This indicates that the core oligosaccharide portion of lipopolysaccharide plays important roles on multiple antibiotic resistance in E. coli and the 1 st heptose in core oligosaccharide portion is critical. Furthermore, the removal of the core oligosaccharide of LPS leads to influences on cell wall morphology, cell phenotypes, porins, efflux systems, and the respond behaviors to antibiotic stimulation. The results demonstrated the important role of lipopolysaccharide on the antibiotic resistance of Gram-negative bacteria.


1997 ◽  
Vol 41 (12) ◽  
pp. 2699-2704 ◽  
Author(s):  
D G White ◽  
K Maneewannakul ◽  
E von Hofe ◽  
M Zillman ◽  
W Eisenberg ◽  
...  

The multiple antibiotic resistance operon (marORAB) in Escherichia coli controls intrinsic susceptibility and resistance to multiple, structurally different antibiotics and other noxious agents. A plasmid construct with marA cloned in the antisense direction reduced LacZ expression from a constitutively expressed marA::lacZ translational fusion and inhibited the induced expression of LacZ in cells bearing the wild-type repressed fusion. The marA antisense construction also decreased the multiple antibiotic resistance of a Mar mutant. Two antisense phosphorothioate oligonucleotides, one targeted to marO and the other targeted to marA of the mar operon, introduced by heat shock or electroporation reduced LacZ expression in the strain having the marA::lacZ fusion. One antisense oligonucleotide, tested against a Mar mutant of E. coli ML308-225, increased the bactericidal activity of norfloxacin. These studies demonstrate the efficacy of exogenously delivered antisense oligonucleotides targeted to the marRAB operon in inhibiting expression of this chromosomal regulatory locus.


2019 ◽  
Vol 31 (3) ◽  
pp. 159-164
Author(s):  
Yaqdhan Alnomani ◽  
Abdolmajid Ghasemian ◽  
Mojtaba Memariani ◽  
Majid Eslami ◽  
Abdolreza Sabokrouh ◽  
...  

2005 ◽  
Vol 49 (7) ◽  
pp. 2746-2752 ◽  
Author(s):  
Anastasia Koutsolioutsou ◽  
Samuel Peña-Llopis ◽  
Bruce Demple

ABSTRACT The soxRS regulon of Escherichia coli and Salmonella enterica is induced by redox-cycling compounds or nitric oxide and provides resistance to superoxide-generating agents, macrophage-generated nitric oxide, antibiotics, and organic solvents. We have previously shown that constitutive expression of soxRS can contribute to quinolone resistance in clinically relevant S. enterica. In this work, we have carried out an analysis of the mechanism of constitutive soxS expression and its role in antibiotic resistance in E. coli clinical isolates. We show that constitutive soxS expression in three out of six strains was caused by single point mutations in the soxR gene. The mutant SoxR proteins contributed to the multiple-antibiotic resistance phenotypes of the clinical strains and were sufficient to confer multiple-antibiotic resistance in a fresh genetic background. In the other three clinical isolates, we observed, for the first time, that elevated soxS expression was not due to mutations in soxR. The mechanism of such increased soxS expression remains unclear. The same E. coli clinical isolates harbored polymorphic soxR and soxS DNA sequences, also seen for the first time.


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