Intrinsic, adaptive and acquired antimicrobial resistance in Gram-negative bacteria

2017 ◽  
Vol 61 (1) ◽  
pp. 49-59 ◽  
Author(s):  
Mohsen Arzanlou ◽  
Wern Chern Chai ◽  
Henrietta Venter
Keyword(s):  
Antimicrobial Resistance ◽  
Molecular Mechanisms ◽  
Resistance Mechanisms ◽  
Stress Conditions ◽  
Gram Negative Bacteria ◽  
Mechanisms Of Resistance ◽  
Intrinsic Resistance ◽  
Antimicrobial Drugs ◽  
Gram Negative ◽  
Gram Negative Organisms

Gram-negative bacteria are responsible for a large proportion of antimicrobial-resistant infections in humans and animals. Among this class of bacteria are also some of the most successful environmental organisms. Part of this success is their adaptability to a variety of different niches, their intrinsic resistance to antimicrobial drugs and their ability to rapidly acquire resistance mechanisms. These mechanisms of resistance are not exclusive and the interplay of several mechanisms causes high levels of resistance. In this review, we explore the molecular mechanisms underlying resistance in Gram-negative organisms and how these different mechanisms enable them to survive many different stress conditions.

scholarly journals Antimicrobial Resistance in Oral biofilm: Challenges and Alternatives

2021 ◽  
Vol 12 (1) ◽  
pp. 349-356
Author(s):  
Satish Kumar Sharma ◽  
Shmmon Ahmad
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Molecular Mechanisms ◽  
Resistance Mechanisms ◽  
Bacterial Biofilm ◽  
Bacterial Biofilms ◽  
Target Cells ◽  
Bacterial Cells ◽  
Antimicrobial Drugs ◽  
Oral Infections

Bacterial biofilm has been a major contributor to severe bacterial infections in humans. Oral infections have also been associated with biofilm-forming microbes. Several antimicrobial strategies have been developed to combat bacterial biofilms. However, the complexity of the oral cavity has made it difficult to use common drug treatments. Most effective ways to control normal bacterial infections are rendered ineffective for bacterial biofilms. Due to limited drug concentration availability, drug neutralization or altered phenotype of bacterial cells, different drug have been ineffective to identify the target cells. This leads to the development of the multifaceted phenomenon of antimicrobial resistance (AMR). Biofilm research done so far has been focused on using antimicrobial drugs to target molecular mechanisms of cells. The severity and resistance mechanisms of extracellular matrix (ECM) have been underestimated. The present study describes different antimicrobial strategies with respect to their applications in dental or oral infections. A prospective strategy has been proposed targeting ECM which is expected to provide an insight on biofilm obstinacy and antimicrobial resistance.

Antimicrobial Resistance in the Intensive Care Unit

2016 ◽  
Vol 32 (1) ◽  
pp. 25-37 ◽  
Author(s):  
Shawn H. MacVane
Keyword(s):  
Intensive Care ◽  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Hospital Costs ◽  
High Morbidity ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Gram Negative Organisms

Bacterial infections are a frequent cause of hospitalization, and nosocomial infections are an increasingly common condition, particularly within the acute/critical care setting. Infection control practices and new antimicrobial development have primarily focused on gram-positive bacteria; however, in recent years, the incidence of infections caused by gram-negative bacteria has risen considerably in intensive care units. Infections caused by multidrug-resistant (MDR) gram-negative organisms are associated with high morbidity and mortality, with significant direct and indirect costs resulting from prolonged hospitalizations due to antibiotic treatment failures. Of particular concern is the increasing prevalence of antimicrobial resistance to β-lactam antibiotics (including carbapenems) among Pseudomonas aeruginosa and Acinetobacter baumannii and, recently, among pathogens of the Enterobacteriaceae family. Treatment options for infections caused by these pathogens are limited. Antimicrobial stewardship programs focus on optimizing the appropriate use of currently available antimicrobial agents with the goals of improving outcomes for patients with infections caused by MDR gram-negative organisms, slowing the progression of antimicrobial resistance, and reducing hospital costs. Newly approved treatment options are available, such as β-lactam/β-lactamase inhibitor combinations, which significantly extend the armamentarium against MDR gram-negative bacteria.

RND efflux pumps in Gram-negative bacteria; regulation, structure and role in antibiotic resistance

2020 ◽  
Vol 15 (2) ◽  
pp. 143-157 ◽  
Author(s):  
Abigail L Colclough ◽  
Ilyas Alav ◽  
Emily E Whittle ◽  
Hannah L Pugh ◽  
Elizabeth M Darby ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Efflux Pumps ◽  
Gram Negative Bacteria ◽  
Bacterial Cells ◽  
Intrinsic Resistance ◽  
Gram Negative ◽  
New Information ◽  
Rnd Efflux Pumps ◽  
Gram Negative Organisms

Rresistance-nodulation-division (RND) efflux pumps in Gram-negative bacteria remove multiple, structurally distinct classes of antimicrobials from inside bacterial cells therefore directly contributing to multidrug resistance. There is also emerging evidence that many other mechanisms of antibiotic resistance rely on the intrinsic resistance conferred by RND efflux. In addition to their role in antibiotic resistance, new information has become available about the natural role of RND pumps including their established role in virulence of many Gram-negative organisms. This review also discusses the recent advances in understanding the regulation and structure of RND efflux pumps.

scholarly journals Fluoroquinolone Metalloantibiotics to Bypass Antimicrobial Resistance Mechanisms: Decreased Permeation through Porins

Membranes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 3
Author(s):  
Mariana Ferreira ◽  
Carla F. Sousa ◽  
Paula Gameiro
Keyword(s):  
Antimicrobial Resistance ◽  
Membrane Permeability ◽  
Resistance Mechanism ◽  
Resistance Mechanisms ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Specific Association ◽  
Location Association

Fluoroquinolones (FQs) are broad-spectrum antibiotics largely used in the clinical practice against Gram-negative and some Gram-positive bacteria. Nevertheless, bacteria have developed several antimicrobial resistance mechanisms against such class of antibiotics. Ternary complexes of FQs, copper(II) and phenanthroline, known as metalloantibiotics, arise in an attempt to counteract an antibiotic resistance mechanism related to low membrane permeability. These metalloantibiotics seem to use an alternative influx route, independent of porins. The translocation pathways of five FQs and its metalloantibiotics were studied through biophysical experiments, allowing us to infer about the role of OmpF porin in the influx. The FQ-OmpF interaction was assessed in mimetic membrane systems differing on the lipidic composition, disclosing no interference of the lipidic composition. The drug-porin interaction revealed similar values for the association constants of FQs and metalloantibiotics with native OmpF. Therefore, OmpF mutants and specific quenchers were used to study the location-association relationship, comparing a free FQ and its metalloantibiotic. The free FQ revealed a specific association, with preference for residues on the centre of OmpF, while the metalloantibiotic showed a random interaction. Thereby, metalloantibiotics may be an alternative to pure FQs, being able to overcome some antimicrobial resistance mechanism of Gram-negative bacteria related to decreased membrane permeability.

scholarly journals Modern problems of antibiotic resistance gram-negative nosocomial infections in the Rostov region

2019 ◽  
Vol 10 (3) ◽  
pp. 91-96 ◽  
Author(s):  
O. Yu. Kutsevalova ◽  
I. O. Pokudina ◽  
D. A. Rozenko ◽  
D. V. Martynov ◽  
M. Yu. Kaminsky
Keyword(s):  
Resistance Mechanisms ◽  
Infectious Complications ◽  
Control Measures ◽  
Gram Negative Bacteria ◽  
Antimicrobial Drugs ◽  
Gram Negative ◽  
Infection Control Measures ◽  
Test Kit ◽  
Extended Spectrum Beta Lactamases ◽  
The City

Objectives: to analyze the prevalence of strains of gram-negative bacteria - pathogens of infectious complications resistant to carbapenems, including through the production of carbapenemases isolated from various clinical biomaterials in hospitalized patients of hospitals in the city of Rostov-on-Don.Materials and methods: 366 gram-negative bacterial isolates were studied, from patients from 16 wards, 9 treatment-and-prophylactic institutions of the city of Rostov-on-Don and the region. The study was conducted by traditional microbiological method. Species identification of strains and sensitivity to antimicrobial drugs were determined on a Vitek 2 automatic analyzer (BioMerieux, France). The strains insensitive to carbapenems were tested for the presence of carbapenemases using CIM-test. MBL was detected by the effect of suppression of their activity in the presence of EDTA. MBL genes were detected by PCR-RV test kit “AmpliSens MDR MBL-FL”, “AmpliSens MDR KPC/OXA-48-FL”. The conclusion about the production of BLRS was made by the presence of synergism of cephalosporins of III-IV generation with clavulanic acid by the method of double discs.Results: of the 366 isolates tested, gram-negative bacteria accounted for 74.2 %: Klebsiella pneumoniae — 33.0 %, Escherichia coli — 19.0 %, Acinetobacter baumannii — 18.0 %, Pseudomonas aeruginosa — 15.0 %. Resistance to carbapenems was detected in 90.9 % of A.baumannii strains, more than 50 % of P.aeruginosa and K.pneumoniae. LBR production was detected in more than 90 % of K.pneumoniae and about 80 % of E. coli. In A. baumannii and K.pneumoniae isolates, the presence of OXA and NDM genes was found, and in P.aeruginosa, VIM groups.Conclusion: enterobacteria resistant to beta-lactams, producing extended-spectrum beta-lactamases and carbapenemases are one of the leading causative agents of infectious complications in hospitals of Rostov-on-don and the region, almost not inferior in frequency of occurrence of bacteria of the genus Acinetobacter spp. and Paeruginosa. This determines the importance of detection of resistance mechanisms not only for the purpose of optimal etiotropic therapy, but also for epidemiological control of the spread of resistant strains and the development of infection control measures.

scholarly journals Epidemiology and Mechanisms of Resistance of Extensively Drug Resistant Gram-Negative Bacteria

Antibiotics ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 37 ◽  
Author(s):  
Emily M. Eichenberger ◽  
Joshua T. Thaden
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Mechanisms ◽  
Individual Treatment ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Mechanisms Of Resistance ◽  
Gram Negative ◽  
Treatment Practices ◽  
Extensively Drug Resistant ◽  
Global Epidemiology

Antibiotic resistance has increased markedly in gram-negative bacteria over the last two decades, and in many cases has been associated with increased mortality and healthcare costs. The adoption of genotyping and next generation whole genome sequencing of large sets of clinical bacterial isolates has greatly expanded our understanding of how antibiotic resistance develops and transmits among bacteria and between patients. Diverse mechanisms of resistance, including antibiotic degradation, antibiotic target modification, and modulation of permeability through the bacterial membrane have been demonstrated. These fundamental insights into the mechanisms of gram-negative antibiotic resistance have influenced the development of novel antibiotics and treatment practices in highly resistant infections. Here, we review the mechanisms and global epidemiology of antibiotic resistance in some of the most clinically important resistance phenotypes, including carbapenem resistant Enterobacteriaceae, extensively drug resistant (XDR) Pseudomonas aeruginosa, and XDR Acinetobacter baumannii. Understanding the resistance mechanisms and epidemiology of these pathogens is critical for the development of novel antibacterials and for individual treatment decisions, which often involve alternatives to β-lactam antibiotics.

scholarly journals The Target of Daptomycin Is Absent from Escherichia coli and Other Gram-Negative Pathogens

2012 ◽  
Vol 57 (1) ◽  
pp. 637-639 ◽  
Author(s):  
Christopher P. Randall ◽  
Katherine R. Mariner ◽  
Ian Chopra ◽  
Alex J. O'Neill
Keyword(s):  
Escherichia Coli ◽  
Antibacterial Activity ◽  
Resistance Mechanisms ◽  
Efflux Transporters ◽  
Permeability Barrier ◽  
Gram Negative Bacteria ◽  
Intrinsic Resistance ◽  
Gram Negative ◽  
Content Type ◽  
E Coli

ABSTRACTAntistaphylococcal agents commonly lack activity against Gram-negative bacteria likeEscherichia coliowing to the permeability barrier presented by the outer membrane and/or the action of efflux transporters. When these intrinsic resistance mechanisms are artificially compromised, such agents almost invariably demonstrate antibacterial activity against Gram negatives. Here we show that this is not the case for the antibiotic daptomycin, whose target appears to be absent fromE. coliand other Gram-negative pathogens.

Antimicrobial Resistance in Enteric Gram-Negative Organisms

2016 ◽  
Author(s):  
Allison Mah ◽  
Inna Sekirov ◽  
Theodore S Steiner
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Resistance ◽  
Clinical Manifestations ◽  
Treatment Strategies ◽  
Resistance Mechanisms ◽  
Current Treatment ◽  
Health Care Use ◽  
Gram Negative ◽  
Gram Negative Organisms ◽  
The Many

Antimicrobial resistance is a phenomenon that predates the introduction of antibiotics into clinical practice and has become an exponentially growing problem worldwide, leading to increased mortality and increased costs of health care use. Among the many organisms with ever-worsening resistance profiles, Escherichia coli and other Enterobacteriaceae species are significant pathogens, both in terms of numbers and the severity of the infections they cause. The purpose of this review is to examine the emerging concern of antimicrobial resistance and the approach to treatment in the setting of infection with resistant organisms. We will focus on the resistance mechanisms of Enterobacteriaceae to select antimicrobial classes, briefly discuss the epidemiology of resistance, and discuss current treatment strategies. The specific epidemiology, clinical manifestations, and treatment of individual members of the Enterobacteriaceae are discussed in the review “Infections Due to Escherichia coli and Other Enteric Gram-Negative Bacilli,” found elsewhere in this publication. Figures illustrate the mechanisms of antimicrobial resitance in Enterobacteriaceae. Tables list the Ambler classification of ESBL/AmpC and carbapenemase enzymes, and antibiotics with activity against carbapenem-resistant enterobacteriaceae. This review contains 4 highly rendered figures, 2 tables, and 27 references.

Success and Challenges Associated with Large Scale Collaborative Surveillance for Carbapenemase Genes in Gram Negative Bacteria

2021 ◽  
Author(s):  
Sanchita Das ◽  
Karen Bush
Keyword(s):  
Antibiotic Resistance ◽  
Antimicrobial Resistance ◽  
Large Scale ◽  
Resistance Mechanisms ◽  
Gram Negative Bacteria ◽  
Routine Laboratory ◽  
Significant Morbidity ◽  
Gram Negative ◽  
Surveillance Studies ◽  
The One

The emergence and spread of antimicrobial resistance, especially in Gram negative bacteria has led to significant morbidity and increased cost of healthcare. Large surveillance studies such as the one performed by the Antibiotic Resistance Laboratory Network are immensely valuable in understanding the scope of resistance mechanisms especially among carbapenemase producing Gram negative bacteria. However, the routine laboratory detection of carbapenemases in these bacteria remain challenging and require further optimization.

Antimicrobial Activity of Iron-Halide Complexes Against Gram-Positive and Gram-Negative Bacteria

2020 ◽  
Author(s):  
Nusrat Abedin ◽  
Abdullah Hamed A Alshehri ◽  
Ali M A Almughrbi ◽  
Olivia Moore ◽  
Sheikh Alyza ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Resistance ◽  
Extracellular Dna ◽  
Antibiofilm Activity ◽  
Gram Negative Bacteria ◽  
Bacterial Strains ◽  
Gram Positive ◽  
Gram Negative ◽  
Antimicrobial Substances ◽  
Mammalian Cell Lines

Antimicrobial resistance (AMR) has become one of the more serious threats to the global health. The emergence of bacteria resistant to antimicrobial substances decreases the potencies of current antibiotics. Consequently, there is an urgent and growing need for the developing of new classes of antibiotics. Three prepared novel iron complexes have a broad-spectrum antimicrobial activity with minimum bactericidal concentration (MBC) values ranging from 3.5 to 10 mM and 3.5 to 40 mM against Gram-positive and Gram-negative bacteria with antimicrobial resistance phenotype, respectively. Time-kill studies and quantification of the extracellular DNA confirmed the bacteriolytic mode of action of the iron-halide compounds. Additionally, the novel complexes showed significant antibiofilm activity against the tested pathogenic bacterial strains at concentrations lower than the MBC. The cytotoxic effect of the complexes on different mammalian cell lines show sub-cytotoxic values at concentrations lower than the minimum bactericidal concentrations.

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