scholarly journals The Atypical Antipsychotic Quetiapine Induces Multiple Antibiotic Resistance in Escherichia coli

2021 ◽  
Author(s):  
Yasuhiro Kyono ◽  
Lori Ellezian ◽  
YueYue Hu ◽  
Kanella Eliadis ◽  
Junlone Moy ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Atypical Antipsychotic ◽  
Sequencing Analysis ◽  
Multiple Antibiotic Resistance ◽  
Minimal Inhibitory Concentrations ◽  
E Coli ◽  
5Ht1a Receptors ◽  
Target Effect

Atypical antipsychotic (AAP) medication is a critical tool for treating symptoms of psychiatric disorders. While AAPs primarily target dopamine (D2) and serotonin (5HT2A and 5HT1A) receptors, they also exhibit intrinsic antimicrobial activity as an off-target effect. Because AAPs are often prescribed to patients for many years, a potential risk associated with long-term AAP use is the unintended emergence of bacteria with antimicrobial resistance (AMR). Here, we show that exposure to the AAP quetiapine at estimated gut concentrations promotes AMR in Escherichia coli after six weeks. Quetiapine-exposed isolates exhibited an increase in minimal inhibitory concentrations (MICs) for ampicillin, tetracycline, ceftriaxone, and levofloxacin. By whole genome sequencing analysis, we identified mutations in genes that confer AMR, including the repressor for the multiple antibiotic resistance mar operon (marR), and real-time RT-qPCR analysis showed increased levels of marA, acrA, and tolC mRNAs and a reduced level of ompF mRNA in the isolates carrying marR mutations. To determine the contribution of each marR mutation to AMR, we constructed isogenic strains carrying individual mutant marR alleles in the parent background and re-evaluated their resistant phenotypes using MIC and RT-qPCR assays. While marR mutations induced a robust activity of the mar operon, they resulted in only a modest increase in MICs. Interestingly, although these marR mutations did not fully recapitulate the AMR phenotype of the quetiapine-exposed isolates, we show that marR mutations promote growth fitness in the presence of quetiapine. Our findings revealed an important link between the use of AAPs and AMR development in E. coli.

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 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

scholarly journals Isolation, Identification and Antibiotic Susceptibility of Escherichia coli Isolated from Raw Meat from Modake and Ile-Ife, Osun State, Nigeria

2021 ◽  
pp. 9-13
Author(s):  
Wilkie Eunice Damilola ◽  
Oluduro Anthonia Olufunke ◽  
Ezeani Chidinma Vivian ◽  
Sotala Toyosi Teniola
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Antibiotic Susceptibility ◽  
Multiple Antibiotic Resistance ◽  
Raw Meat ◽  
E Coli ◽  
Antibiotic Susceptibility Test ◽  
Mueller Hinton Agar ◽  
Meat Samples ◽  
High Level

The study reported isolation, identification and antibiotic susceptibility of Escherichia coli isolated from raw meat from Modakeke and Ile-ife, Osun State, Nigeria, with the view to determining the antibiogram profiling of the bacterial isolates.  In this study, five samples of fresh meat were collected from different abattoirs in Ile-Ife and Modakeke, Osun State. Isolates of Escherichia coli were isolated, identified morphologically based on their growth on nutrient agar and subjected to antibiotic susceptibility test on Mueller Hinton agar. The mean microbial load from the meat samples ranged from 8.85 x 102cfu/ml to 5.77 x 104cfu/ml. A total of 69 E. coli isolates were recovered from the meat sampled. All the isolates appeared cream, translucent, entire, convex, circular, smooth and glistering. The isolates were identified as Gram negative rods, non-motile, lactose fermenters, positive for indole test and negative for citrate utilization test. All the E. coli isolates were resistant to augmentin, ceftriazone, nitrofurantoin and gentamycin. 98.55% of E. coli isolated was resistant to amoxillin and the least resistant was recorded in ofloxacin (8.70%). However, 91.30% of the E. coli isolates was sensitive to ofloxacin, 81.16% to ciprofloxacin and 36.23% to pefloxacin while none was sensitive to augmentin, ceftriazone, nitrofurantoin and gentamycin. A total of 19 different multiple antibiotic resistance patterns were observed among the isolates. Thirty isolates (43.48%) showed multiple antibiotic resistance to 5 and 10 different antibiotic types each. The study concluded that occurrence of E. coli infection is high in the study area with high level of multiple antibiotic resistance.

scholarly journals Multidrug Resistance following Expression of the Escherichia coli marA Gene in Mycobacterium smegmatis

1998 ◽  
Vol 180 (11) ◽  
pp. 2995-2998 ◽  
Author(s):  
Patrick F. McDermott ◽  
David G. White ◽  
Isabelle Podglajen ◽  
Michael N. Alekshun ◽  
Stuart B. Levy
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Multidrug Resistance ◽  
Mycobacterium Smegmatis ◽  
Antimicrobial Agents ◽  
Regulatory System ◽  
Mutant Protein ◽  
Multiple Antibiotic Resistance ◽  
Alpha Helices ◽  
E Coli

ABSTRACT Expression of the Escherichia coli multiple antibiotic resistance marA gene cloned in Mycobacterium smegmatis produced increased resistance to multiple antimicrobial agents, including rifampin, isoniazid, ethambutol, tetracycline, and chloramphenicol. Cloned marR or marA cloned in the antisense direction had no effect. Resistance changes were lost with spontaneous loss of the plasmid bearing marA. A MarA mutant protein, having an insertional mutation within either of its two alpha-helices of the first putative helix-turn-helix domain, failed to produce the multiresistance phenotype in E. coli andM. smegmatis, indicating that this region is critical for MarA function. These results strongly suggest that E. coli marA functions in M. smegmatis and that amar-like regulatory system exists in this organism.

scholarly journals Antibiotic susceptibility pattern of Escherichia coli isolated from food, cooking utensils and palms of food handlers in some restaurants in Zaria, Nigeria

2021 ◽  
Vol 1 (2) ◽  
pp. 28-34
Author(s):  
Victoria Etalong ◽  
Babajide A. Tytler ◽  
Igba Profit ◽  
Adeshina O. Gbonjubola
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Antibiotic Susceptibility ◽  
Resistance Index ◽  
Major Public Health Problem ◽  
Multiple Antibiotic Resistance ◽  
Food Handlers ◽  
Susceptibility Pattern ◽  
Antibiotic Susceptibility Pattern ◽  
E Coli

Foodborne disease is a major public health problem causing considerable morbidity and mortality annually. In the present study, the antibiotic susceptibility patterns of Escherichia coli isolated from food, cooking utensils and palms of food handlers in some restaurants in Zaria, Nigeria were evaluated. A total of 250 samples (220 food samples, 7 hand samples of food handlers, 10 plate samples within restaurants and 13 spoon samples) were collected from five locations in Zaria, Nigeria and analysed for microbial contaminations using standard microbiological techniques. The antibiotic susceptibility pattern of the isolates was determined using Kirby-Bauer modified disc agar diffusion technique. Results revealed that out of 158 acclaimed Enterobacteriaceae isolates evaluated, 19 % (30) were confirmed to be E. coli, while 81 % were Klebsiella. spp, Citrobacter fruendii, Enterobacter spp, Shigella spp, Salmonella spp, Serratia spp, and Cronobacter sakazaki. The majority of the isolates were resistant to amoxiclav (26.08%), ampicillin (26.08%), tetracycline (26.08%) and metronidazole (13.04%). A 33.3% of the isolates were multidrug-resistant. The E. coli isolates were mostly multiple antibiotic resistance with 43.3% having multiple antibiotic resistance index (MARI) ≥ 0.2. In conclusion, E. coli evolved resistance to ampicillin, Amoxicillin Clavulanic acid, and Tetracycline and other tested antimicrobial drugs which would make the treatment of Escherichia coli infections difficult

scholarly journals Multiple antibiotic resistance (mar) locus protects Escherichia coli from rapid cell killing by fluoroquinolones.

1996 ◽  
Vol 40 (5) ◽  
pp. 1266-1269 ◽  
Author(s):  
J D Goldman ◽  
D G White ◽  
S B Levy
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Bactericidal Activity ◽  
Cell Killing ◽  
Deletion Mutants ◽  
Multiple Antibiotic Resistance ◽  
Wild Type ◽  
E Coli ◽  
High Concentrations

The multiple antibiotic resistance (mar) locus in Escherichia coli consists of two divergently expressed operons (marC and marRAB), both of which contribute to the Mar phenotype. Overexpression of the marRAB operon protected E. coli against rapid cell killing by fluoroquinolones. Inactivation of the operon in mar mutants restored a wild-type bactericidal susceptibility. Both operons of the locus were required for protection from the quinolone-mediated bactericidal activity in mar locus deletion mutants. The effect was lost at high concentrations of fluoroquinolones, unlike the case for the previously described genes hipA and hipQ. The inducible mar locus appears to specify a novel antibactericidal mechanism which may play a role in the emergence of fluoroquinolone-resistant clinical E. coli isolates.

ANTIBIOTIC SUSCEPTIBILITY OF BACTERIAL STRAINS, WITH SPECIAL REFERENCE TO ESCHERICHIA COLI ISOLATED FROM URINARY TRACT INFECTIONS IN RURAL MAHARASHTRA

2016 ◽  
Vol 10 (1) ◽  
pp. 202
Author(s):  
Sunil Shivaputrayya Gidamudi ◽  
Gaurav V Salunke
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Multiple Antibiotic Resistance ◽  
Bacterial Strains ◽  
Cross Sectional ◽  
E Coli ◽  
Sensitivity Pattern ◽  
Tract Infections

ABSTRACTObjective: The objective of this study was to find out the etiology of urinary tract infections (UTIs) in patients attending B.K.L. Walawalkar Hospital,Dervan and to determine their antibiotic sensitivity pattern to currently used antimicrobial agents.Methods: A cross-sectional study was conducted in a rural hospital of Konkan Maharashtra, and urine samples were collected from368 clinically - suspected cases of UTIs using the mid-stream “clean catch” method and was tested and cultured using standard procedures. Antimicrobialsusceptibility test (AST) was performed for the isolated pathogens according to the Clinical and Laboratory Standards Institute guidelines.Results: Escherichia coli (54.84%) was the most prevalent uropathogen. 76.47% of the isolated E. coli were found to be extended spectrum betalactamase producers. A higher prevalence rate of resistance was seen among E. coli to the commonly prescribed antibiotic agents. 32 (94.11%) of34 E. coli isolates recovered had multiple antibiotic resistance (MAR), with 16 isolates (50%) possessing MAR indices of 0.6.Conclusion: The study indicates the isolated microorganisms in UTI showed very high resistance to the commonly prescribed antimicrobial drugs.This suggests the monitoring and rational use of the antimicrobial agents.Keywords: Mid-stream, Culture, Uropathogen, Resistance, Multiple antibiotic resistance.

The Escherichia coli multiple antibiotic resistance activator protein represses transcription of the lac operon

2019 ◽  
Vol 47 (2) ◽  
pp. 671-677
Author(s):  
Anna Lankester ◽  
Shafayeth Ahmed ◽  
Lisa E. Lamberte ◽  
Rachel A. Kettles ◽  
David C. Grainger
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Efflux Pump ◽  
Regulatory Region ◽  
Lac Operon ◽  
Multiple Antibiotic Resistance ◽  
E Coli ◽  
Genes Encoding ◽  
Response Systems ◽  
A Site

AbstractIn Escherichia coli, the marRAB operon is a determinant for antibiotic resistance. Such phenotypes require the encoded transcription factor MarA that activates efflux pump expression. To better understand all genes controlled by MarA, we recently mapped binding of the regulator across the E. coli genome. As expected, many MarA targets were adjacent to genes encoding stress response systems. Surprisingly, one MarA-binding site overlapped the lac operon regulatory region. Here, we show that MarA specifically targets this locus and can block transcription of the lac genes. Repression is mediated by binding of MarA to a site overlapping the lacP1 promoter −35 element. Control of the lac operon by MarA does not impact antibiotic resistance.

scholarly journals Multiple Antibiotic Resistance Patterns ofEscherichia coli Isolates from Swine Farms

1999 ◽  
Vol 65 (6) ◽  
pp. 2770-2772 ◽  
Author(s):  
A. G. Mathew ◽  
A. M. Saxton ◽  
W. G. Upchurch ◽  
S. E. Chattin
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Antibiotic Use ◽  
Ofescherichia Coli ◽  
Multiple Antibiotic Resistance ◽  
E Coli ◽  
Swine Farms ◽  
Resistance Patterns ◽  
Antibiotic Resistance Patterns ◽  
Farm Types

ABSTRACT Antibiotic resistance of Escherichia coli from sows and pigs was determined to compare patterns between pigs of various ages and degrees of antibiotic use. Resistance patterns differed between farm types and pigs of differing ages, indicating that pig age and degree of antibiotic use affect resistance of fecal E. coli.

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