scholarly journals The Periplasmic Murein Peptide-Binding Protein MppA Is a Negative Regulator of Multiple Antibiotic Resistance in Escherichia coli

1999 ◽  
Vol 181 (16) ◽  
pp. 4842-4847 ◽  
Author(s):  
HongShan Li ◽  
James T. Park
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Binding Protein ◽  
Wide Spectrum ◽  
Negative Regulator ◽  
Null Mutant ◽  
Multiple Antibiotic Resistance ◽  
Resistance Phenotype ◽  
E Coli ◽  
K 12

ABSTRACT MppA is a periplasmic binding protein in Escherichia coli essential for uptake of the cell wall murein tripeptidel-alanyl-γ-d-glutamyl-meso-diaminopimelate. We have found serendipitously that E. coli K-12 strains carrying a null mutation in mppA exhibit increased resistance to a wide spectrum of antibiotics and to cyclohexane. Normal sensitivity of the mppA mutant to these agents is restored by mppA expressed from a plasmid. As is observed in the multiple antibiotic resistance phenotype in E. coli cells, the mppA null mutant overproduces the transcriptional activator, MarA, resulting in expression of the membrane-bound AcrAB proteins that function as a drug efflux pump. Reduced production of OmpF similar to that observed in the multiple antibiotic resistance phenotype is also seen in the mppA mutant. These and other data reported herein indicate that MppA functions upstream of MarA in a signal transduction pathway to negatively regulate the expression ofmarA and hence of the MarA-driven multiple antibiotic resistance. Overproduction of cytoplasmic GadA and GadB and of several unidentified cytoplasmic membrane proteins as well as reduction in the amount of the outer membrane protein, OmpP, in the mppAnull mutant indicate that MppA regulates a number of genes in addition to those already known to be controlled by MarA.

scholarly journals Increased Survival of Antibiotic-Resistant Escherichia coli inside Macrophages

2012 ◽  
Vol 57 (1) ◽  
pp. 189-195 ◽  
Author(s):  
Migla Miskinyte ◽  
Isabel Gordo
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Resistance Mutation ◽  
Fitness Cost ◽  
Resistance Mutations ◽  
Content Type ◽  
E Coli ◽  
Fitness Effects ◽  
K 12

ABSTRACTMutations causing antibiotic resistance usually incur a fitness cost in the absence of antibiotics. The magnitude of such costs is known to vary with the environment. Little is known about the fitness effects of antibiotic resistance mutations when bacteria confront the host's immune system. Here, we study the fitness effects of mutations in therpoB,rpsL, andgyrAgenes, which confer resistance to rifampin, streptomycin, and nalidixic acid, respectively. These antibiotics are frequently used in the treatment of bacterial infections. We measured two important fitness traits—growth rate and survival ability—of 12Escherichia coliK-12 strains, each carrying a single resistance mutation, in the presence of macrophages. Strikingly, we found that 67% of the mutants survived better than the susceptible bacteria in the intracellular niche of the phagocytic cells. In particular, allE. colistreptomycin-resistant mutants exhibited an intracellular advantage. On the other hand, 42% of the mutants incurred a high fitness cost when the bacteria were allowed to divide outside of macrophages. This study shows that single nonsynonymous changes affecting fundamental processes in the cell can contribute to prolonged survival ofE. coliin the context of an infection.

scholarly journals Inhibition of the multiple antibiotic resistance (mar) operon in Escherichia coli by antisense DNA analogs.

1997 ◽  
Vol 41 (12) ◽  
pp. 2699-2704 ◽  
Author(s):  
D G White ◽  
K Maneewannakul ◽  
E von Hofe ◽  
M Zillman ◽  
W Eisenberg ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Antisense Oligonucleotides ◽  
Multiple Antibiotic Resistance ◽  
Wild Type ◽  
Lacz Expression ◽  
E Coli ◽  
Plasmid Construct ◽  
Dna Analogs ◽  
Susceptibility And Resistance

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.

scholarly journals Constitutive soxR Mutations Contribute to Multiple-Antibiotic Resistance in Clinical Escherichia coli Isolates

2005 ◽  
Vol 49 (7) ◽  
pp. 2746-2752 ◽  
Author(s):  
Anastasia Koutsolioutsou ◽  
Samuel Peña-Llopis ◽  
Bruce Demple
Keyword(s):  
Nitric Oxide ◽  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Dna Sequences ◽  
Single Point ◽  
Constitutive Expression ◽  
Clinical Isolates ◽  
Multiple Antibiotic Resistance ◽  
E Coli ◽  
First Time

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.

scholarly journals Detection of virulence genes, phylogenetic group and antibiotic resistance of uropathogenic Escherichia coli in Mongolia

2017 ◽  
Vol 11 (01) ◽  
pp. 51-57 ◽  
Author(s):  
Yandag Munkhdelger ◽  
Nyamaa Gunregjav ◽  
Altantsetseg Dorjpurev ◽  
Nishi Juniichiro ◽  
Jav Sarantuya
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Virulence Genes ◽  
Wide Spectrum ◽  
Iron Acquisition ◽  
Uropathogenic Escherichia Coli ◽  
Phylogenetic Group ◽  
Diffusion Method ◽  
Phylogenetic Groups ◽  
E Coli

Introduction: The severity of urinary tract infection (UTI) produced by uropathogenic Escherichia coli (UPEC) is due to the expression of a wide spectrum of virulence genes. E. coli strains were divided into four phylogenetic groups (A, B1, B2 and D) based on their virulence genes. The present study aimed to assess the relationship between virulence genes, phylogenetic groups, and antibiotic resistance of UPEC. Methodology: A total of 148 E. coli were tested for antimicrobial resistance against 10 drugs using the disk diffusion method. The isolates were screened by polymerase chain reaction (PCR) for detection of virulence genes and categorized into the four major phylogenetic groups. Results: Phylogenetic group B2 was predominant (33.8%), followed by D (28.4%), A (19.6), and B1 (18.2%). A higher prevalence of fimH (89.9%), fyuA (70.3%), traT (66.2%), iutA (62.2%), kpsMTII (58.8%), and aer (56.1%) genes were found in UPEC, indicating a putative role of adhesins, iron acquisition systems, and protectins that are main cause of UTIs. The most common antibiotic resistance was to cephalotin (85.1%), ampicillin (78.4%) and the least to nitrofurantoin (5.4%) and imipenem (2%). In total, 93.9% of isolates were multidrug resistant (MDR). Conclusions: This study showed that group B2 and D were the predominant phylogenetic groups and virulence-associated genes were mostly distributed in these groups. The virulence genes encoding components of adhesins, iron acquisition systems, and protectins were highly prevalent among antibiotic-resistant UPEC. Although the majority of strains are MDR, nitrofurantoin is the drug of choice for treatment of UTI patients in Ulaanbaatar.

scholarly journals Extended Spectrum Beta Lactamases Detection and Multiple Antibiotic Resistance Indexing of Escherichia Coli from Urine Samples of Patients from a Referral Hospital of Eastern Nepal

2015 ◽  
Vol 3 (3) ◽  
pp. 423-426 ◽  
Author(s):  
A. Chakrawarti ◽  
P. Dongol ◽  
H. Khanal ◽  
P. Subba ◽  
J.J. Benerjee
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Urine Samples ◽  
Multiple Antibiotic Resistance ◽  
Beta Lactamases ◽  
E Coli ◽  
Extended Spectrum Beta Lactamases ◽  
Mar Index ◽  
Esbl Producers ◽  
Disc Assay

Background: Escherichia coli is the most common causative agent of urinary tract infection. Antibiotic resistance among uropathogens has become a prominent public health problem. Multidrug resistance bacteria have limited the therapeutic possibilities by producing Extended Spectrum Beta Lactamases (ESBL). Objective: Since routine monitoring of ESBL producers are not conducted in clinical laboratories their true prevalence is still unknown. So the objective of this research was to assess multiple antibiotic resistance (MAR) indices and determine ESBL production among Escherichia coli isolated from urine samples. Methods: Standard microbiological techniques and antibiotic sensitivity test were performed by Kirby Bauer disc diffusion method to identify E. coli. ESBL screening was done by using Ceftriaxone, Aztreonam, Cefotaxime, Ceftazidime and Cefpodoxime whereas confirmation by combined disc assay. SPSS 16 software was used to analyze data. Results: 86.95% E. coli isolates were MDR strains. 27 isolates had multiple antibiotic resistance (MAR) index of 0.2 and 5 isolates had MAR index of 0.7. E. coli isolates showed higher degree of resistance towards Amoxicillin (100%) while 100% were sensitive towards Gentamicin followed by Nitrofurantoin (62.31%). The reliable screening agent for ESBL detection with sensitivity 100% and positive predictive value of 80% was Cefotaxime. Combined disc assay detected 12/69 (17.31%) of E. coli isolates as confirmed ESBL producers. Conclusion: The ubiquity of ESBL-producing E. coli was observed emphasizing the necessity of regular surveillance of ESBL producing clinical isolates in clinical samples to minimize multi-drug resistance strains and avert the ineffectiveness of antimicrobial agent for good health practices.\Int J Appl Sci Biotechnol, Vol 3(3): 423-426

Core oligosaccharide portion of lipopolysaccharide plays important roles on multiple antibiotic resistance in Escherichia coli

2021 ◽  
Author(s):  
Jianli Wang ◽  
Wenjian Ma ◽  
Yu Fang ◽  
Hao Liang ◽  
Huiting Yang ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Cell Envelope ◽  
Gene Clusters ◽  
Gram Negative Bacteria ◽  
Multiple Antibiotic Resistance ◽  
Core Oligosaccharide ◽  
Gram Negative ◽  
The Core ◽  
K 12

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.

scholarly journals The Conjugation Window in an Escherichia coli K-12 Strain with an IncFII Plasmid

2020 ◽  
Vol 86 (17) ◽  
Author(s):  
Brendan Headd ◽  
Scott A. Bradford
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Antibiotic Resistance Genes ◽  
Time Frame ◽  
Environmental Aspect ◽  
Content Type ◽  
E Coli ◽  
Donor Cells ◽  
K 12 ◽  
Regulatory Controls

ABSTRACT Many studies have examined the role that conjugation plays in disseminating antibiotic resistance genes in bacteria. However, relatively little research has quantitively examined and modeled the dynamics of conjugation under growing and nongrowing conditions beyond a couple of hours. We therefore examined growing and nongrowing cultures of Escherichia coli over a 24-h period to understand the dynamics of bacterial conjugation in the presence and absence of antibiotics with pUUH239.2, an IncFII plasmid containing multiantibiotic- and metal-resistant genes. Our data indicate that conjugation occurs after E. coli cells divide and before they have transitioned to a nongrowing phase. The result is that there is only a small window of opportunity for E. coli to conjugate with pUUH239.2 under both growing and nongrowing conditions. Only a very small percentage of the donor cells likely are capable of even undergoing conjugation, and not all transconjugants can become donor cells due to molecular regulatory controls and not being in the correct growth phase. Once a growing culture enters stationary phase, the number of capable donor cells decreases rapidly and conjugation slows to produce a plateau. Published models did not provide accurate descriptions of conjugation under nongrowing conditions. We present here a modified modeling approach that accurately describes observed conjugation behavior under growing and nongrowing conditions. IMPORTANCE There has been growing interest in horizontal gene transfer of antibiotic resistance plasmids as the antibiotic resistance crisis has worsened over the years. Most studies examining conjugation of bacterial plasmids focus on growing cultures of bacteria for short periods, but in the environment, most bacteria grow episodically and at much lower rates than in the laboratory. We examined conjugation of an IncFII antibiotic resistance plasmid in E. coli under growing and nongrowing conditions to understand the dynamics of conjugation under which the plasmid is transferred. We found that conjugation occurs in a narrow time frame when E. coli is transitioning from a growing to nongrowing phase and that the conjugation plateau develops because of a lack of capable donor cells in growing cultures. From an environmental aspect, our results suggest that episodic growth in nutrient-depleted environments could result in more conjugation than sustained growth in a nutrient rich environment.

scholarly journals The Periplasmic Protein MppA Requires an Additional Mutated Locus To Repress marA Expression in Escherichia coli

2003 ◽  
Vol 185 (4) ◽  
pp. 1465-1469 ◽  
Author(s):  
Xiaowen Bina ◽  
Vincent Perreten ◽  
Stuart B. Levy
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Antibiotic Susceptibility ◽  
Type Strain ◽  
Wild Type Strain ◽  
Binding Protein ◽  
Periplasmic Protein ◽  
Multiple Antibiotic Resistance ◽  
Wild Type ◽  
Expression In Escherichia Coli

ABSTRACT Escherichia coli strain TP985, which has an insertional mutation in the gene for the periplasmic murein tripeptide binding protein MppA, was previously reported to overproduce MarA and exhibit a multiple-antibiotic resistance (Mar) phenotype (H. Li and J. T. Park, J. Bacteriol. 181:4842-4847, 1999). We found that TP985 contained a previously unrecognized marR mutation which was responsible for the Mar phenotype. Transduction of the mppA mutation from TP985 to another wild-type strain did not affect antibiotic susceptibility. Overproduction of MppA repressed marA transcription in TP985 but not in other mppA or marR mutants. Therefore, TP985 contains an additional unknown mutation(s) that facilitates the repression of marA expression by MppA.

scholarly journals Alteration of the Repressor Activity of MarR, the Negative Regulator of the Escherichia coli marRAB Locus, by Multiple Chemicals In Vitro

1999 ◽  
Vol 181 (15) ◽  
pp. 4669-4672 ◽  
Author(s):  
Michael N. Alekshun ◽  
Stuart B. Levy
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Sodium Salicylate ◽  
Negative Regulator ◽  
Multiple Antibiotic Resistance ◽  
Whole Cells ◽  
Repressor Activity

ABSTRACT MarR negatively regulates expression of the multiple antibiotic resistance operon (marRAB) in Escherichia coli. In this study, it was demonstrated that sodium salicylate, plumbagin, 2,4-dinitrophenol, and menadione–inducers of the marRABoperon in whole cells–all interfered with the repressor activity of MarR in vitro. It is proposed that these compounds can interact directly with MarR to affect its repressor activity.

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