scholarly journals The Rho-Dependent Transcription Termination Is Involved in Broad-Spectrum Antibiotic Susceptibility in Escherichia coli

2020 ◽  
Vol 11 ◽  
Author(s):  
Md. Hafeezunnisa ◽  
Ranjan Sen
Keyword(s):  
Broad Spectrum ◽  
Antibiotic Susceptibility ◽  
Transcription Termination ◽  
Efflux Pumps ◽  
Dependent Manner ◽  
Broad Spectrum Antibiotic ◽  
E Coli ◽  
Distinct Cell ◽  
High Level ◽  
Termination Function

One of the major ways of acquiring multidrug resistance in bacteria is via drug influx and efflux pathways. Here, we show that E. coli with compromised Rho-dependent transcription termination function has enhanced broad-spectrum antibiotic susceptibility, which arises from the inefficient TolC-efflux process and increased permeability of the membrane. The Rho mutants have altered morphology, distinct cell surface, and increased levels of lipopolysaccharide in their outer membrane, which might have rendered the TolC efflux pumps inefficient. These alterations are due to the upregulations of poly-N-acetyl-glucosamine and lipopolysaccharide synthesis operons because of inefficient Rho functions. The Rho mutants are capable of growing on various dipeptides and carbohydrate sources, unlike their WT counterpart. Dipeptides uptake arises from the upregulations of the di-peptide permease operon in these mutants. The metabolomics of the Rho mutants revealed the presence of a high level of novel metabolites. Accumulation of these metabolites in these Rho mutants might titrate out the TolC-efflux pumps, which could further reduce their efficiency. We conclude that the transcription termination factor, Rho, regulates the broad-spectrum antibiotic susceptibility of E. coli through multipartite pathways in a TolC-dependent manner. The involvement of Rho-dependent termination in multiple pathways and its association with antibiotic susceptibility should make Rho-inhibitors useful in the anti-bacterial treatment regimen.

scholarly journals Resistance and Virulence Mechanisms of Escherichia coli Selected by Enrofloxacin in Chicken

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Jun Li ◽  
Haihong Hao ◽  
Menghong Dai ◽  
Heying Zhang ◽  
Jianan Ning ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Efflux Pumps ◽  
Genetic Alterations ◽  
Site Directed Mutagenesis ◽  
Single Mutation ◽  
Genetic Characteristics ◽  
Content Type ◽  
E Coli ◽  
Low Level ◽  
High Level

ABSTRACT This study aimed to investigate the genetic characteristics, antibiotic resistance patterns, and novel mechanisms involved in fluoroquinolone (FQ) resistance in commensal Escherichia coli isolates. The E. coli isolates were recovered from a previous clinical study and subjected to antimicrobial susceptibility testing and molecular typing. Known mechanisms of FQ resistance (target site mutations, plasmid-mediated quinolone resistance [PMQR] genes, relative expression levels of efflux pumps and porins) were detected using DNA sequencing of PCR products and real-time quantitative PCR. Whole-genome shotgun sequencing was performed on 11 representative strains to screen for single nucleotide polymorphisms (SNPs). The function of a key SNP (A1541G) was investigated by site-directed mutagenesis and allelic exchange. The results showed that long-term enrofloxacin treatment selected multidrug-resistant (MDR) E. coli isolates in the chicken gut and that these E. coli isolates had diverse genetic backgrounds. Multiple genetic alterations, including double mutations on GyrA (S83L and D87N), a single mutation on ParC (S80I) and ParE (S458E), activation of efflux pumps, and the presence of the QnrS1 protein, contributed to the high-level FQ resistance (enrofloxacin MIC [MICENR] ≥ 128 μg/ml), while the relatively low-level FQ resistance (MICENR = 8 or 16 μg/ml) was commonly mediated by decreased expression of the porin OmpF, besides enhancement of the efflux pumps. No significant relationship was observed between resistance mechanisms and virulence genes. Introduction of the A1541G mutation on aegA was able to increase FQ susceptibility by 2-fold. This study contributes to a better understanding of the development of MDR and the differences underlying the mechanisms of high-level and low-level FQ resistance in E. coli.

scholarly journals Polyamine Effects on Antibiotic Susceptibility in Bacteria

2007 ◽  
Vol 51 (6) ◽  
pp. 2070-2077 ◽  
Author(s):  
Dong-Hyeon Kwon ◽  
Chung-Dar Lu
Keyword(s):  
Synergistic Effect ◽  
Outer Membrane ◽  
Antibiotic Susceptibility ◽  
Efflux Pump ◽  
Population Analysis ◽  
Enteric Bacteria ◽  
Dependent Manner ◽  
E Coli ◽  
Serovar Typhimurium ◽  
Exogenous Spermine

ABSTRACT Biogenic polyamines (e.g., spermidine and spermine) are a group of essential polycationic compounds found in all living cells. The effects of spermine and spermidine on antibiotic susceptibility were examined with gram-negative Escherichia coli and Salmonella enterica serovar Typhimurium bacteria and clinical isolates of Pseudomonas aeruginosa and with gram-positive Staphylococcus aureus bacteria, including methicillin-resistant S. aureus (MRSA). Exogenous spermine exerted a dose-dependent inhibition effect on the growth of E. coli, S. enterica serovar Typhimurium, and S. aureus but not P. aeruginosa, as depicted by MIC and growth curve measurements. While the MICs of polymyxin and ciprofloxacin were in general increased by exogenous spermine and spermidine in P. aeruginosa, this adverse effect was not observed in enteric bacteria and S. aureus. It was found that spermine and spermidine can decrease the MICs of β-lactam antibiotics in all strains as well as other types of antibiotics in a strain-dependent manner. Significantly, the MICs of oxacillin for MRSA Mu50 and N315 were decreased more than 200-fold in the presence of spermine, and this effect of spermine was retained when assessed in the presence of divalent ions (magnesium or calcium; 3 mM) or sodium chloride (150 mM). The effect of spermine on the sensitization of P. aeruginosa and MRSA to antibiotics was further demonstrated by population analysis and time-killing assays. The results of checkerboard assays with E. coli and S. aureus indicated a strong synergistic effect of spermine in combination with β-lactams and chloramphenicol. The decreased MICs of β-lactams implied that the possible blockage of outer membrane porins by exogenous spermine or spermidine did not play a crucial role in most cases. In contrast, only the MIC of imipenem against P. aeruginosa was increased by exogenous spermine and spermidine, and this resistance effect was abolished in a mutant strain devoid of the outer membrane porin OprD. In E. coli, the MICs of carbenicillin, chloramphenicol, and tetracycline were decreased in two acrA mutants devoid of a major efflux pump, AcrAB. However, retention of the spermine effect on antibiotic susceptibility in two acrA mutants of E. coli suggested that the AcrAB efflux pump was not the target for a synergistic effect by spermine and antibiotics and ruled out the hypothesis of spermine serving as an efflux pump inhibitor in this organism. In summary, this interesting finding of the effect of spermine on antibiotic susceptibility provides the basis for a new potential approach against drug-resistant pathogens by use of existing β-lactam antibiotics.

High-level colonisation of the human gut by Verrucomicrobia following broad-spectrum antibiotic treatment

2013 ◽  
Vol 41 (2) ◽  
pp. 149-155 ◽  
Author(s):  
Grégory Dubourg ◽  
Jean-Christophe Lagier ◽  
Fabrice Armougom ◽  
Catherine Robert ◽  
Gilles Audoly ◽  
...  
Keyword(s):  
Antibiotic Treatment ◽  
Broad Spectrum ◽  
Broad Spectrum Antibiotic ◽  
Human Gut ◽  
High Level

EFFECTS OF PENICILLIN AND BROAD-SPECTRUM ANTIBIOTICS ON THE EMERGENCE OF A GRAM-NEGATIVE BACILLARY FLORA IN THE UPPER RESPIRATORY TRACT OF INFANTS

PEDIATRICS ◽  
1952 ◽  
Vol 9 (5) ◽  
pp. 572-576
Author(s):  
ROBERT S. MCCURDY ◽  
ERWIN NETER
Keyword(s):  
Respiratory Tract ◽  
Broad Spectrum ◽  
Clinical Manifestations ◽  
Upper Respiratory Tract ◽  
Broad Spectrum Antibiotic ◽  
Gram Negative ◽  
E Coli ◽  
Broad Spectrum Antibiotics ◽  
Upper Respiratory ◽  
Aerobic Flora

A study was undertaken on 107 infants to determine the effect of penicillin and broad-spectrum antibiotics (aureomycin, chloromycetin and terramycin), alone and in combination, on the emergence of a predominant gram-negative, bacillary flora of the upper respiratory tract. The following data were obtained: 1. Such a change of the flora took place in 4 out of 12 patients treated with penicillin, 15 out of 22 treated with penicillin and a broad-spectrum antibiotic, and in only 4 out of 21 infants who received a broad-spectrum antibiotic exclusively. 2. Of the 32 cases whose flora had thus changed, members of the E. coli-A. aerogenes group were found in 30 instances, members of the genus Proteus in 3; Ps. aeruginosa in 2; Paracolobactrum in 1; and combinations thereof in four cases. 3. This change of the flora took place in 18 out of 71 infants suffering from respiratory infection and in 14 out of 36 children suffering from other diseases. 4. Reappearance of clinical manifestations was observed in 6 out of 19 patients whose respiratory tract flora changed following the use of penicillin and in none of the four individuals who were treated with a broad-spectrum antibiotic alone. In view of the small number of cases this observation requires confirmation. 5. It is concluded that in infants the use of penicillin used in conjunction with a broad-spectrum antibiotic is followed rather frequently by the emergence in the upper respiratory tract of a predominant gram-negative, bacillary, aerobic flora; such a change occurs less frequently after the use of a broad-spectrum antibiotic alone. The clinical significance of these data is discussed.

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 244. Impact of Antibiotic Susceptibility Reporting on Broad-Spectrum Antibiotic Use in Serratia and Morganella Bacteremia

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S104-S104
Author(s):  
Wendy Hui Wen Ng ◽  
Joy Yong ◽  
Ka Lip Chew ◽  
Janice Li ◽  
MClin Pharm
Keyword(s):  
Broad Spectrum ◽  
Antibiotic Susceptibility ◽  
Antibiotic Use ◽  
Broad Spectrum Antibiotic

scholarly journals Potent Broad-Spectrum Antibacterial Activity of Amphiphilic Peptides against Multidrug-Resistant Bacteria

2020 ◽  
Vol 8 (9) ◽  
pp. 1398 ◽  
Author(s):  
Yuan Liu ◽  
Jingru Shi ◽  
Ziwen Tong ◽  
Yuqian Jia ◽  
Kangni Yang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antibacterial Activity ◽  
Broad Spectrum ◽  
Multidrug Resistant ◽  
Drug Candidate ◽  
Resistant Bacteria ◽  
Dependent Manner ◽  
Gram Negative ◽  
E Coli ◽  
Amphiphilic Peptide

The emergence and prevalence of multidrug-resistant (MDR) bacteria particularly Gram-negative bacteria presents a global crisis for human health. Colistin and tigecycline were recognized as the last resort of defenses against MDR Gram-negative pathogens. However, the emergence and prevalence of MCR or Tet(X)-mediated acquired drug resistance drastically impaired their clinical efficacy. It has been suggested that antimicrobial peptides might act a crucial role in combating antibiotic resistant bacteria owing to their multiple modes of action and characteristics that are not prone to developing drug resistance. Herein, we report a safe and stable tryptophan-rich amphiphilic peptide termed WRK-12 with broad-spectrum antibacterial activity against various MDR bacteria, including MRSA, colistin and tigecycline-resistant Escherichia coli. Mechanistical studies showed that WRK-12 killed resistant E. coli through permeabilizing the bacterial membrane, dissipating membrane potential and triggering the production of reactive oxygen species (ROS). Meanwhile, WRK-12 significantly inhibited the formation of an E. coli biofilm in a dose-dependent manner. These findings revealed that amphiphilic peptide WRK-12 is a promising drug candidate in the fight against MDR bacteria.

scholarly journals Broad spectrum antibiotic use among in-patients at a hospital in Nairobi, Kenya

2018 ◽  
Vol 8 (1) ◽  
pp. 1
Author(s):  
Kizito M. Mariita ◽  
Harriet A. Chirima ◽  
Carol K. Maina
Keyword(s):  
Broad Spectrum ◽  
Respiratory Tract Infections ◽  
Antibiotic Use ◽  
Global Public Health ◽  
Broad Spectrum Antibiotic ◽  
E Coli ◽  
Co Morbidity ◽  
Tract Infections ◽  
Study Participants ◽  
Age Range

Background: Antimicrobial resistance is an increasingly serious threat to global public health. While the use of antibiotics is an important contributing factor, there are gaps regarding this in our region. This study aimed to describe the use of nine broad spectrum antibiotics among in-patients of The Nairobi Hospital (TNH) so as to identify opportunities for quality improvement.Methods: This was a retrospective review of the use of meropenem, ertapenem, imipenem, cefepime, piperacillin, gentamicin, amikacin, vancomycin and teicoplanin among in-patients of TNH from 1st January 2018 to 31st March 2018. Demographic and clinical data of all in-patients who were prescribed these antibiotics during the study period were retrieved from patient files.Results: There were 301 study participants with a median age (range) of 30years (1day-74years), of whom 161 (53.5%) were male. More than half of the participants were admitted for less than one week and had at least one co-morbidity. Meropenem was the most commonly prescribed study antibiotic 123 (40.9%) followed by amikacin 89 (29.6%). Respiratory tract infections 125 (41.5%) were the predominant indications. Meropenem had the longest mean duration of administration, 6.5days while the aminoglycosides were administered for a relatively shorter duration of about 4.8days. Cultures were done on 187 (62.1%) patients though it is only samples of 45 patients that grew an organism, E. coli and Klebsiella sp being the most frequently isolated organisms.Conclusions: There’s a need to strongly intensify implementation of restriction strategies for Meropenem use and introduction of education programs on antimicrobial stewardship targeting all prescribers.

scholarly journals Factors essential for L,D-transpeptidase-mediated peptidoglycan cross-linking and β-lactam resistance in Escherichia coli

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Jean-Emmanuel Hugonnet ◽  
Dominique Mengin-Lecreulx ◽  
Alejandro Monton ◽  
Tanneke den Blaauwen ◽  
Etienne Carbonnelle ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Broad Spectrum ◽  
Cell Walls ◽  
Cross Linking ◽  
Penicillin Binding Proteins ◽  
E Coli ◽  
Class A ◽  
Cross Links ◽  
High Level

The target of β-lactam antibiotics is the D,D-transpeptidase activity of penicillin-binding proteins (PBPs) for synthesis of 4→3 cross-links in the peptidoglycan of bacterial cell walls. Unusual 3→3 cross-links formed by L,D-transpeptidases were first detected in Escherichia coli more than four decades ago, however no phenotype has previously been associated with their synthesis. Here we show that production of the L,D-transpeptidase YcbB in combination with elevated synthesis of the (p)ppGpp alarmone by RelA lead to full bypass of the D,D-transpeptidase activity of PBPs and to broad-spectrum β-lactam resistance. Production of YcbB was therefore sufficient to switch the role of (p)ppGpp from antibiotic tolerance to high-level β-lactam resistance. This observation identifies a new mode of peptidoglycan polymerization in E. coli that relies on an unexpectedly small number of enzyme activities comprising the glycosyltransferase activity of class A PBP1b and the D,D-carboxypeptidase activity of DacA in addition to the L,D-transpeptidase activity of YcbB.

scholarly journals The Co-occurrence of NDM-5, MCR-1, and FosA3-Encoding Plasmids Contributed to the Generation of Extensively Drug-Resistant Klebsiella pneumoniae

2022 ◽  
Vol 12 ◽  
Author(s):  
Ying Zhou ◽  
Wenxiu Ai ◽  
Yanhua Cao ◽  
Yinjuan Guo ◽  
Xiaocui Wu ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Efflux Pumps ◽  
Drug Resistant ◽  
E Coli ◽  
Extensively Drug Resistant ◽  
Antimicrobial Resistance Genes ◽  
Rnd Efflux Pumps ◽  
Comparative Genetic Analysis ◽  
High Level ◽  
Almost All

The rise and global dissemination of extensively drug-resistant (XDR) bacteria are often related to plasmid-borne mobile antimicrobial resistance genes. Notably, isolates having multiple plasmids are often highly resistant to almost all the antibiotics available. In this study, we characterized an extensively drug-resistant Klebsiella pneumoniae 1678, which exhibited high-level resistance to almost all the available antibiotics. Through whole-genome sequencing (WGS), more than 20 resistant elements and 5 resistant plasmids were observed. Notably, the tigecycline resistance of K. pneumoniae 1678 was not related to the plasmid-borne tetA gene but associated with the overexpression of AcrAB and OqxAB efflux pumps, according to the susceptibility results of tetA-transformant and the related mRNA quantification of RND efflux pumps. Except for tigecycline resistance, three plasmids, mediating resistance to colistin, Fosfomycin, and ceftazidime–avibactam, respectively, were focused. Detailed comparative genetic analysis showed that all these plasmids belonged to dominated epidemic plasmids, and harbored completed conjugation systems. Results of conjugation assay indicated that these three plasmids not only could transfer to E. coli J53 with high conjugation frequencies, respectively, but also could co-transfer to E. coli J53 effectively, which was additionally confirmed by the S1-PFGE plasmids profile. Moreover, multiple insertion sequences (IS) and transposons (Tn) were also found surrounding the vital resistant genes, which may form several novel mechanisms involved in the resistant determinants’ mobilization. Overall, we characterized and reported the uncommon co-existence and co-transferring of FosA3-, NDM-5, and MCR-1-encoding plasmids in a K. pneumoniae isolate, which may increase the risk of spread of these resistant phenotypes and needing great concern.

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