scholarly journals Post-Covid-19 Era: What is Next?

2021 ◽  
Author(s):  
Shiela Chetri
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
Multidrug Efflux Pump ◽  
High Risk Factors ◽  
Clinical Complications

Antimicrobial resistance (AMR) is a natural phenomenon in bacteria which becomes a threat for health-care settings around the world. A concerted global response is needed to tackle rising rates of antibiotic resistance, without it we risk returning to the pre antibiotic era. As bacteria evolve very fast according to the environment in which they inhabit via developing different defence mechanisms to combat with the noxious agents like different classes of antibiotics including carbapenems. This results into treatment failure and clinical complications. Global emergence of antibiotic resistance due to bacterial multidrug efflux pump systems are a major and common mechanism of intrinsic antimicrobial resistance employed by bacteria which are spreading rapidly due to over use or misuse of antimicrobial agents. This review mainly focusses on the transcriptional expression of efflux pump system AcrAB-TolC, local regulatory genes (AcrR and AcrS), mediating carbapenem resistance in clinical isolates of Escherichia coli under antibiotic stress, a genetic interplay study between intrinsic and acquired antibiotic resistance mechanisms along with a brief summary on high risk factors and prevalence of urinary tract infections by multidrug resistant Uropathogenic Escherichia coli.

scholarly journals Efflux Pump Mediated Antimicrobial Resistance by Staphylococci in Health-Related Environments: Challenges and the Quest for Inhibition

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1502
Author(s):  
Abolfazl Dashtbani-Roozbehani ◽  
Melissa H. Brown
Keyword(s):  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Current Knowledge ◽  
Efflux Pumps ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Multidrug Efflux Pump ◽  
New Antibiotics ◽  
Efflux Pump Inhibitors

The increasing emergence of antimicrobial resistance in staphylococcal bacteria is a major health threat worldwide due to significant morbidity and mortality resulting from their associated hospital- or community-acquired infections. Dramatic decrease in the discovery of new antibiotics from the pharmaceutical industry coupled with increased use of sanitisers and disinfectants due to the ongoing COVID-19 pandemic can further aggravate the problem of antimicrobial resistance. Staphylococci utilise multiple mechanisms to circumvent the effects of antimicrobials. One of these resistance mechanisms is the export of antimicrobial agents through the activity of membrane-embedded multidrug efflux pump proteins. The use of efflux pump inhibitors in combination with currently approved antimicrobials is a promising strategy to potentiate their clinical efficacy against resistant strains of staphylococci, and simultaneously reduce the selection of resistant mutants. This review presents an overview of the current knowledge of staphylococcal efflux pumps, discusses their clinical impact, and summarises compounds found in the last decade from plant and synthetic origin that have the potential to be used as adjuvants to antibiotic therapy against multidrug resistant staphylococci. Critically, future high-resolution structures of staphylococcal efflux pumps could aid in design and development of safer, more target-specific and highly potent efflux pump inhibitors to progress into clinical use.

scholarly journals Mechanisms Accounting for Fluoroquinolone Resistance in Escherichia coli Clinical Isolates

2008 ◽  
Vol 53 (1) ◽  
pp. 235-241 ◽  
Author(s):  
Sonia K. Morgan-Linnell ◽  
Lauren Becnel Boyd ◽  
David Steffen ◽  
Lynn Zechiedrich
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Resistance Mechanisms ◽  
Clinical Isolates ◽  
Fluoroquinolone Resistance ◽  
Multidrug Efflux Pump ◽  
Topoisomerase Iv ◽  
E Coli ◽  
Genes Encoding

ABSTRACT Fluoroquinolone MICs are increased through the acquisition of chromosomal mutations in the genes encoding gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE), increased levels of the multidrug efflux pump AcrAB, and the plasmid-borne genes aac(6′)-Ib-cr and the qnr variants in Escherichia coli. In the accompanying report, we found that ciprofloxacin, gatifloxacin, levofloxacin, and norfloxacin MICs for fluoroquinolone-resistant E. coli clinical isolates were very high and widely varied (L. Becnel Boyd, M. J. Maynard, S. K. Morgan-Linnell, L. B. Horton, R. Sucgang, R. J. Hamill, J. Rojo Jimenez, J. Versalovic, D. Steffen, and L. Zechiedrich, Antimicrob. Agents Chemother. 53:229-234, 2009). Here, we sequenced gyrA, gyrB, parC, and parE; screened for aac(6′)-Ib-cr and qnrA; and quantified AcrA levels in E. coli isolates for which patient sex, age, location, and site of infection were known. We found that (i) all fluoroquinolone-resistant isolates had gyrA mutations; (ii) ∼85% of gyrA mutants also had parC mutations; (iii) the ciprofloxacin and norfloxacin MICs for isolates harboring aac(6′)-Ib-cr (∼23%) were significantly higher, but the gatifloxacin and levofloxacin MICs were not; (iv) no isolate had qnrA; and (v) ∼33% of the fluoroquinolone-resistant isolates had increased AcrA levels. Increased AcrA correlated with nonsusceptibility to the fluoroquinolones but did not correlate with nonsusceptibility to any other antimicrobial agents reported from hospital antibiograms. Known mechanisms accounted for the fluoroquinolone MICs of 50 to 70% of the isolates; the remaining included isolates for which the MICs were up to 1,500-fold higher than expected. Thus, additional, unknown fluoroquinolone resistance mechanisms must be present in some clinical isolates.

scholarly journals Klebsiella pneumoniae Major Porins OmpK35 and OmpK36 Allow More Efficient Diffusion of β-Lactams than Their Escherichia coli Homologs OmpF and OmpC

2016 ◽  
Vol 198 (23) ◽  
pp. 3200-3208 ◽  
Author(s):  
Etsuko Sugawara ◽  
Seiji Kojima ◽  
Hiroshi Nikaido
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Outer Membrane ◽  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Resistance Mechanisms ◽  
Fourth Generation ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Content Type

ABSTRACTKlebsiella pneumoniae, one of the most important nosocomial pathogens, is becoming a major problem in health care because of its resistance to multiple antibiotics, including cephalosporins of the latest generation and, more recently, even carbapenems. This is largely due to the spread of plasmid-encoded extended-spectrum β-lactamases. However, antimicrobial agents must first penetrate the outer membrane barrier in order to reach their targets, and hydrophilic and charged β-lactams presumably diffuse through the porin channels. Unfortunately, the properties ofK. pneumoniaeporin channels are largely unknown. In this study, we made clean deletions ofK. pneumoniaeporin genesompK35andompK36and examined the antibiotic susceptibilities and diffusion rates of β-lactams. The results showed that OmpK35 and OmpK36 produced larger more permeable channels than theirEscherichia colihomologs OmpF and OmpC; OmpK35 especially produced a diffusion channel of remarkably high permeability toward lipophilic (benzylpenicillin) and large (cefepime) compounds. These results were also confirmed by expressing various porins in anE. colistrain lacking major porins and the major multidrug efflux pump AcrAB. Our data explain why the development of drug resistance inK. pneumoniaeis so often accompanied by the mutational loss of its porins, especially OmpK35, in addition to the various plasmid-carried genes of antibiotic resistance, because even hydrolysis by β-lactamases becomes inefficient in producing high levels of resistance if the bacterium continues to allow a rapid influx of β-lactams through its wide porin channels.IMPORTANCEIn Gram-negative bacteria, drugs must first enter the outer membrane, usually through porin channels. Thus, the quantitative examination of influx rates is essential for the assessment of resistance mechanisms, yet no such studies exist for a very important nosocomial pathogen,Klebsiella pneumoniae. We found that the larger channel porin of this organism, OmpK35, produces a significantly larger channel than itsEscherichia colihomolog, OmpF. This makes unmodifiedK. pneumoniaestrains more susceptible to relatively large antibiotics, such as the third- and fourth-generation cephalosporins. Also, even the acquisition of powerful β-lactamases is not likely to make them fully resistant in the presence of such an effective influx process, explaining why so many clinical isolates of this organism lack porins.

scholarly journals Impact of Feed Supplementation with Antimicrobial Agents on Growth Performance of Broiler Chickens, Clostridium perfringens and Enterococcus Counts, and Antibiotic Resistance Phenotypes and Distribution of Antimicrobial Resistance Determinants in Escherichia coli Isolates

2007 ◽  
Vol 73 (20) ◽  
pp. 6566-6576 ◽  
Author(s):  
Moussa S. Diarra ◽  
Fred G. Silversides ◽  
Fatoumata Diarrassouba ◽  
Jane Pritchard ◽  
Luke Masson ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Antimicrobial Resistance ◽  
Broiler Chickens ◽  
Antimicrobial Agents ◽  
Growth Promoters ◽  
Feed Supplementation ◽  
E Coli ◽  
Resistance Determinants ◽  
Class 1

ABSTRACT The effects of feed supplementation with the approved antimicrobial agents bambermycin, penicillin, salinomycin, and bacitracin or a combination of salinomycin plus bacitracin were evaluated for the incidence and distribution of antibiotic resistance in 197 commensal Escherichia coli isolates from broiler chickens over 35 days. All isolates showed some degree of multiple antibiotic resistance. Resistance to tetracycline (68.5%), amoxicillin (61.4%), ceftiofur (51.3%), spectinomycin (47.2%), and sulfonamides (42%) was most frequent. The levels of resistance to streptomycin, chloramphenicol, and gentamicin were 33.5, 35.5, and 25.3%, respectively. The overall resistance levels decreased from day 7 to day 35 (P < 0.001). Comparing treatments, the levels of resistance to ceftiofur, spectinomycin, and gentamicin (except for resistance to bacitracin treatment) were significantly higher in isolates from chickens receiving feed supplemented with salinomycin than from the other feeds (P < 0.001). Using a DNA microarray analysis capable of detecting commonly found antimicrobial resistance genes, we characterized 104 tetracycline-resistant E. coli isolates from 7- to 28-day-old chickens fed different growth promoters. Results showed a decrease in the incidence of isolates harboring tet(B), bla TEM, sulI, and aadA and class 1 integron from days 7 to 35 (P < 0.01). Of the 84 tetracycline-ceftiofur-resistant E. coli isolates, 76 (90.5%) were positive for bla CMY-2. The proportions of isolates positive for sulI, aadA, and integron class 1 were significantly higher in salinomycin-treated chickens than in the control or other treatment groups (P < 0.05). These data demonstrate that multiantibiotic-resistant E. coli isolates can be found in broiler chickens regardless of the antimicrobial growth promoters used. However, the phenotype and the distribution of resistance determinants in E. coli can be modulated by feed supplementation with some of the antimicrobial agents used in broiler chicken production.

Antimicrobial Resistance and Association with Class 1 Integrons in Escherichia coli Isolated from Turkey Meat Products

2008 ◽  
Vol 71 (8) ◽  
pp. 1679-1684 ◽  
Author(s):  
M. L. KHAITSA ◽  
J. OLOYA ◽  
D. DOETKOTT ◽  
R. KEGODE
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
Population Attributable Fraction ◽  
Meat Products ◽  
Resistance Mechanisms ◽  
E Coli ◽  
Class 1 Integrons ◽  
Turkey Meat ◽  
Class 1

The objective of this study was to quantify the role of class 1 integrons in antimicrobial resistance in Escherichia coli isolated from turkey meat products purchased from retail outlets in the Midwestern United States. Of 242 E. coli isolates, 41.3% (102 of 242) tested positive for class 1 integrons. A significant association was shown between presence of class 1 integrons in E. coli isolates and the resistance to tetracycline, ampicillin, streptomycin, gentamicin, sulfisoxazole, and trimethoprim-sulfamethoxazole. Attributable risk analysis revealed that for every 100 E. coli isolates carrying class 1 integrons, resistance was demonstrated for ampicillin (22%), gentamycin (48%), streptomycin (29%), sulfisoxazole (40%), trimethoprimsulfamethoxazole (7%), and tetracycline (26%). Non–integron-related antimicrobial resistance was demonstrated for ampicillin (65%), gentamycin (16.9%), streptomycin (42.1%), sulfisoxazole (35.8%), and tetracycline (49.7%). Population-attributable fraction analysis showed that class 1 integrons accounted for the following resistances: gentamycin, 71% (50 of 71), amoxicillin–clavulanic acid, 19.6% (6 of 33), nalidixic acid, 34% (7 of 21), streptomycin, 28% (30 of 107), sulfisoxazole, 38% (40 of 106), and tetracycline, 14%, (26 of 185). In conclusion, although class 1 integrons have been implicated in resistance to antimicrobial agents, other non–integron resistance mechanisms seem to play an important part.

scholarly journals Molecular Characteristics and Antimicrobial Susceptibility Profile of Pseudomonas aeruginosa isolated from patients attending Healthcare Facilities in Mthatha, South Africa

2020 ◽  
Author(s):  
Mojisola C. Hosu ◽  
Sandeep D. Vasaikar ◽  
Grace E. Okuthe ◽  
teke apalata
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
Resistance Mechanisms ◽  
High Rate ◽  
Infection Prevention And Control ◽  
Molecular Characteristics ◽  
Mortality And Morbidity ◽  
Resistance Patterns

Abstract Background: Pseudomonas aeruginosa is a common pathogen causing healthcare-associated infections most especially in critically ill and immunocompromised patients. This pathogen poses a public health threat due to its innate resistance to many antimicrobial agents and its ability to acquire new resistance mechanisms under pressure. Infections with Extended spectrum β-lactamases (ESBL)‑producing isolates result into outbreaks that lead to serious antibiotic management concerns with higher mortality and morbidity and significant economic causatives. In this study, we evaluated the antimicrobial resistance patterns and characterized genetically the ESBLs and Metallo- β-lactamases (MBL) produced by this pathogen. Methods: Isolates of P. aeruginosa cultured from patients who attended Nelson Mandela Academic Hospital and other clinics in the four district municipalities of the Eastern Cape between August 2017 and May 2019 were identified; and their antibiotic resistance patterns were tested against amikacin, aztreonam, cefepime, ceftazidime, ciprofloxacin, doripenem, gentamicin, imipenem, levofloxacin, meropenem, piperacillin, piperacillin/tazobactam and tobramycin using the bioMérieux VITEK® 2 and confirmed by Beckman autoSCAN-4 System. Real-time PCR was done using Roche Light Cycler 2.0 to detect the presence of ESBLs; blaSHV, blaTEM and blaCTX-M genes; and MBLs; blaIMP, blaVIM. Results: High antibiotic resistance in decreasing order was observed in piperacillin (64.2%), aztreonam (57.8%), cefepime (51.5%), ceftazidime (51.0%), piperacillin/tazobactam (50.5%), and imipenem (46.6%). A total of 75 (36.8%) multidrug resistant (MDR) isolates were observed of the total pool of isolates. The blaTEM, blaSHV and blaCTX-M was detected in 79.3%, 69.5% and 31.7% isolates (n=82), respectively. The blaIMP was detected in 1.25% while no blaVIM was detected in any of the isolates tested. Conclusions: The study showed a high rate of MDR P. aeruginosa in our setting. The vast majority of these resistant isolates carried blaTEM and blaSHV genes. Continuous monitoring of antimicrobial resistance and strict compliance towards infection prevention and control practices are the best defence against spread of MDR P. aeruginosa.

scholarly journals Cross-Linked Complex between Oligomeric Periplasmic Lipoprotein AcrA and the Inner-Membrane-Associated Multidrug Efflux Pump AcrB from Escherichia coli

2000 ◽  
Vol 182 (15) ◽  
pp. 4264-4267 ◽  
Author(s):  
Helen I. Zgurskaya ◽  
Hiroshi Nikaido
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Intact Cells ◽  
Inner Membrane ◽  
Oligomeric Form ◽  
Chemical Cross Linking ◽  
Multidrug Efflux System

ABSTRACT In Escherichia coli, the intrinsic levels of resistance to multiple antimicrobial agents are produced through expression of the three-component multidrug efflux system AcrAB-TolC. AcrB is a proton-motive-force-dependent transporter located in the inner membrane, and AcrA and TolC are accessory proteins located in the periplasm and the outer membrane, respectively. In this study, these three proteins were expressed separately, and the interactions between them were analyzed by chemical cross-linking in intact cells. We show that AcrA protein forms oligomers, most probably trimers. In this oligomeric form, AcrA interacts specifically with AcrB transporter independently of substrate and TolC.

scholarly journals Prevalence and Antimicrobial Resistance of DiarrheagenicEscherichia coliandShigellaSpecies Associated with Acute Diarrhea in Tehran, Iran

2009 ◽  
Vol 20 (3) ◽  
pp. e56-e62 ◽  
Author(s):  
Fereshteh Jafari ◽  
Mohammad Hamidian ◽  
Maryam Rezadehbashi ◽  
Michael Doyle ◽  
Siavosh Salmanzadeh-ahrabi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Antimicrobial Resistance ◽  
Shiga Toxin ◽  
Acute Diarrhea ◽  
Antimicrobial Agents ◽  
High Rate ◽  
Appropriate Use ◽  
E Coli ◽  
Etiological Agents

A study was performed to determine the prevalence and antimicrobial resistance ofShigellaspecies and diarrheagenicEscherichia coliisolates cultured from patients with acute diarrhea in Tehran, Iran. Between May 2003 and May 2005, 1120 diarrheal specimens were collected and assayed for bacterial enteropathogens by conventional and molecular methods. Etiological agents were isolated from 564 (50.3%) specimens, and included 305 (54%)E coli, 157 (27.8%)Shigellaspecies, and 102 (18%) from other genera of bacteria. The predominantE coliwas Shiga toxin-producingE coli(105 isolates [34.5%]) and the predominantShigellaserotype wasShigella sonnei(88 isolates [56.1%]). A high rate of antibiotic resistance was observed amongE coli,with 40 of 53 (75.5%) Shiga toxin-producingE coliisolates resistant to amoxicillin and tetra-cycline, and eight (5.2%)E coliisolates resistant to more than six antibiotics. MostShigellaisolates were resistant to tetracycline (95%) and trimethoprim-sulfamethoxazole (91.7%), with greatest antibiotic resistance observed amongS sonnei(53 of 88 [60.2%] isolates). Antibiotic resistance is widespread in diarrheagenicE coliandShigellain children with acute diarrhea in Tehran, Iran; hence, updated strategies for appropriate use of antimicrobial agents in Iran are needed.

scholarly journals Induction of Multidrug Resistance Mechanism in Escherichia coli Biofilms by Interplay between Tetracycline and Ampicillin Resistance Genes

2009 ◽  
Vol 53 (11) ◽  
pp. 4628-4639 ◽  
Author(s):  
Thithiwat May ◽  
Akinobu Ito ◽  
Satoshi Okabe
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Marker Genes ◽  
Ampicillin Resistance ◽  
High Level ◽  
Biofilm Development ◽  
Level Resistance

ABSTRACT Biofilms gain resistance to various antimicrobial agents, and the presence of antibiotic resistance genes is thought to contribute to a biofilm-mediated antibiotic resistance. Here we showed the interplay between the tetracycline resistance efflux pump TetA(C) and the ampicillin resistance gene (bla TEM-1) in biofilms of Escherichia coli harboring pBR322 in the presence of the mixture of ampicillin and tetracycline. E. coli in the biofilms could obtain the high-level resistance to ampicillin, tetracycline, penicillin, erythromycin, and chloramphenicol during biofilm development and maturation as a result of the interplay between the marker genes on the plasmids, the increase of plasmid copy number, and consequently the induction of the efflux systems on the bacterial chromosome, especially the EmrY/K and EvgA/S pumps. In addition, we characterized the overexpression of the TetA(C) pump that contributed to osmotic stress response and was involved in the induction of capsular colanic acid production, promoting formation of mature biofilms. However, this investigated phenomenon was highly dependent on the addition of the subinhibitory concentrations of antibiotic mixture, and the biofilm resistance behavior was limited to aminoglycoside antibiotics. Thus, marker genes on plasmids played an important role in both resistance of biofilm cells to antibiotics and in formation of mature biofilms, as they could trigger specific chromosomal resistance mechanisms to confer a high-level resistance during biofilm formation.

scholarly journals Effectiveness of Efflux Pump Inhibitors as Biofilm Disruptors and Resistance Breakers in Gram-negative (ESKAPEE) Bacteria

2019 ◽  
Author(s):  
Akif Reza ◽  
J. Mark Sutton ◽  
Khondaker Miraz Rahman
Keyword(s):  
Antibiotic Resistance ◽  
Antimicrobial Resistance ◽  
Efflux Pump ◽  
Protein Structures ◽  
Underlying Mechanism ◽  
Resistance Mechanisms ◽  
Healthcare Provision ◽  
Gram Negative ◽  
Environmental Threats ◽  
Efflux Pump Inhibitors

Antibiotic resistance represents a significant threat to the modern healthcare provision. The ESKAPEE pathogens, in particular, have proven to be especially challenging to treat, due to their intrinsic and acquired ability to rapidly develop resistance mechanisms in response to environmental threats. The development of biofilm has been characterised as an essential contributing factor towards antimicrobial-resistance and tolerance. Several studies have implicated the involvement of efflux pumps in antibiotic resistance, both directly, via drug extrusion and indirectly, through the formation of biofilm. As a result, the underlying mechanism of these pumps has attracted considerable interest due to the potential of targeting these protein structures and developing novel adjunct therapies. Subsequent investigations have revealed the ability of efflux pump-inhibitors (EPIs) to block drug-extrusion and disrupt biofilm formation, thereby, potentiating antibiotics and reversing resistance of pathogen towards them. This review will discuss the potential of EPIs as a possible solution to antimicrobial resistance, examining different challenges to the design of these compounds, with an emphasis on Gram-negative ESKAPEE pathogens.

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