scholarly journals Screening for Quorum-Sensing Inhibitors (QSI) by Use of a Novel Genetic System, the QSI Selector

2005 ◽  
Vol 187 (5) ◽  
pp. 1799-1814 ◽  
Author(s):  
Thomas Bovbjerg Rasmussen ◽  
Thomas Bjarnsholt ◽  
Mette Elena Skindersoe ◽  
Morten Hentzer ◽  
Peter Kristoffersen ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Genetic System ◽  
Garlic Extract ◽  
Resistant Bacteria ◽  
Antimicrobial Drugs ◽  
Synthetic Compound ◽  
Compound Libraries ◽  
Promising Target ◽  
Increasing Demand ◽  
Biofilm Development

ABSTRACT With the widespread appearance of antibiotic-resistant bacteria, there is an increasing demand for novel strategies to control infectious diseases. Furthermore, it has become apparent that the bacterial life style also contributes significantly to this problem. Bacteria living in the biofilm mode of growth tolerate conventional antimicrobial treatments. The discovery that many bacteria use quorum-sensing (QS) systems to coordinate virulence and biofilm development has pointed out a new, promising target for antimicrobial drugs. We constructed a collection of screening systems, QS inhibitor (QSI) selectors, which enabled us to identify a number of novel QSIs among natural and synthetic compound libraries. The two most active were garlic extract and 4-nitro-pyridine-N-oxide (4-NPO). GeneChip-based transcriptome analysis revealed that garlic extract and 4-NPO had specificity for QS-controlled virulence genes in Pseudomonas aeruginosa. These two QSIs also significantly reduced P. aeruginosa biofilm tolerance to tobramycin treatment as well as virulence in a Caenorhabditis elegans pathogenesis model.

scholarly journals Antibacterial properties of Allium sativum L. against the most emerging multidrug-resistant bacteria and its synergy with antibiotics

2021 ◽  
Author(s):  
Agnieszka Magryś ◽  
Alina Olender ◽  
Dorota Tchórzewska
Keyword(s):  
Bacterial Infections ◽  
Allium Sativum ◽  
Antibacterial Properties ◽  
Multidrug Resistant ◽  
Garlic Extract ◽  
Resistant Bacteria ◽  
Antimicrobial Drugs ◽  
Healthcare Settings ◽  
Study Results

AbstractGarlic has long been known as the most effective plant species in treatment of bacterial infections. Considering the vast potential of garlic as a source of antimicrobial drugs, this study is aimed to evaluate the antibacterial activity of Allium sativum extracts and their interactions with selected antibiotics against drug-sensitive and multidrug-resistant isolates of emerging bacterial pathogens that are frequently found in healthcare settings. As shown by the in vitro data obtained in this study, the whole Allium sativum extract inhibited the growth of a broad range of bacteria, including multidrug-resistant strains with bactericidal or bacteriostatic effects. Depending on the organism, the susceptibility to fresh garlic extract was comparable to the conventional antibiotic gentamycin. Since the combinations of fresh garlic extract with gentamycin and ciprofloxacin inhibited both the drug sensitive and MDR bacteria, in most cases showing a synergistic or insignificant relationship, the potential use of such combinations may be beneficial, especially in inhibiting drug-resistant pathogens. The study results indicate the possibility of using garlic as e.g. a supplement used during antibiotic therapy, which may increase the effectiveness of gentamicin and ciprofloxacin.

scholarly journals Oral Biofilm: Development Mechanism, Multidrug Resistance, and Their Effective Management with Novel Techniques

2021 ◽  
Vol 12 (1) ◽  
pp. e0004
Author(s):  
Shakti Rath ◽  
◽  
Sourav Chandra Bidyasagar Bal ◽  
Debasmita Dubey ◽  
◽  
...  
Keyword(s):  
Oral Cavity ◽  
Dental Plaque ◽  
Resistant Bacteria ◽  
Effective Management ◽  
Oral Biofilm ◽  
Antimicrobial Drugs ◽  
Drug Resistant Bacteria ◽  
Health Related ◽  
Biofilm Development ◽  
Normal Microbial Flora

Biofilms are formed by the congregation of one or more types of microorganisms that can grow on a firm surface. Dental plaque is one of the most commonly forming biofilms in the oral cavity and appears as a slimy layer on the surface of the teeth. In general, the formation is slow, but biofilms are very adaptive to the changing environment, and a mature biofilm can cause many health-related problems in humans. These biofilms remain unaffected by antibiotics as they do not allow the penetration of antibiotics. Moreover, the increased level of virulence and antibiotic resistance of microorganisms in the oral biofilm or dental plaque has made its clinical management a serious clinical challenge worldwide. Chlorhexidine-like antimicrobial drugs have been partially effective in removing such organisms; however, the precise and continuous elimination of these microorganisms without disturbing the normal microbial flora of the oral cavity is still a challenge. This paper focuses on the process of oral biofilm formation, related complications, development of drug-resistant bacteria in these biofilms, and their effective management by the use of different novel techniques.

Identification of a Potential Inhibitor Targeting MurC Ligase of the Drug Resistant Pseudomonas aeruginosa Strain through Structure-Based Virtual Screening Approach and In Vitro Assay

2019 ◽  
Vol 20 (14) ◽  
pp. 1203-1212
Author(s):  
Abdelmonaem Messaoudi ◽  
Manel Zoghlami ◽  
Zarrin Basharat ◽  
Najla Sadfi-Zouaoui
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virtual Screening ◽  
Homology Model ◽  
Generation Cephalosporin ◽  
World Health ◽  
Resistant Bacteria ◽  
Antimicrobial Drugs ◽  
Vitro Assay ◽  
Priority List

Background & Objective: Pseudomonas aeruginosa shows resistance to a large number of antibiotics, including carbapenems and third generation cephalosporin. According to the World Health Organization global report published in February 2017, Pseudomonas aeruginosa is on the priority list among resistant bacteria, for which new antibiotics are urgently needed. Peptidoglycan serves as a good target for the discovery of novel antimicrobial drugs. Methods: Biosynthesis of peptidoglycan is a multi-step process involving four mur enzymes. Among these enzymes, UDP-N-acetylmuramate-L-alanine ligase (MurC) is considered to be an excellent target for the design of new classes of antimicrobial inhibitors in gram-negative bacteria. Results: In this study, a homology model of Pseudomonas aeruginosa MurC ligase was generated and used for virtual screening of chemical compounds from the ZINC Database. The best screened inhibitor i.e. N, N-dimethyl-2-oxo-2,3-dihydro-1H-1,3-benzodiazole-5-sulfonamide was then validated experimentally through inhibition assay. Conclusion: The presented results based on combined computational and in vitro analysis open up new horizons for the development of novel antimicrobials against this pathogen.

scholarly journals Assessing the Molecular Targets and Mode of Action of Furanone C-30 on Pseudomonas aeruginosa Quorum Sensing

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1620
Author(s):  
Victor Markus ◽  
Karina Golberg ◽  
Kerem Teralı ◽  
Nazmi Ozer ◽  
Esti Kramarsky-Winter ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Quorum Sensing ◽  
Conformational Changes ◽  
Mode Of Action ◽  
Pathogenic Bacteria ◽  
Molecular Targets ◽  
Resistant Bacteria ◽  
Public Healthcare ◽  
C 30

Quorum sensing (QS), a sophisticated system of bacterial communication that depends on population density, is employed by many pathogenic bacteria to regulate virulence. In view of the current reality of antibiotic resistance, it is expected that interfering with QS can address bacterial pathogenicity without stimulating the incidence of resistance. Thus, harnessing QS inhibitors has been considered a promising approach to overriding bacterial infections and combating antibiotic resistance that has become a major threat to public healthcare around the globe. Pseudomonas aeruginosa is one of the most frequent multidrug-resistant bacteria that utilize QS to control virulence. Many natural compounds, including furanones, have demonstrated strong inhibitory effects on several pathogens via blocking or attenuating QS. While the natural furanones show no activity against P. aeruginosa, furanone C-30, a brominated derivative of natural furanone compounds, has been reported to be a potent inhibitor of the QS system of the notorious opportunistic pathogen. In the present study, we assess the molecular targets and mode of action of furanone C-30 on P. aeruginosa QS system. Our results suggest that furanone C-30 binds to LasR at the ligand-binding site but fails to establish interactions with the residues crucial for the protein’s productive conformational changes and folding, thus rendering the protein dysfunctional. We also show that furanone C-30 inhibits RhlR, independent of LasR, suggesting a complex mechanism for the agent beyond what is known to date.

scholarly journals Multidrug Resistence Prevalence in COVID Area

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 601
Author(s):  
Caterina Aurilio ◽  
Pasquale Sansone ◽  
Antonella Paladini ◽  
Manlio Barbarisi ◽  
Francesco Coppolino ◽  
...  
Keyword(s):  
Bacterial Resistance ◽  
Respiratory Infections ◽  
Prolonged Mechanical Ventilation ◽  
Viral Disease ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antimicrobial Drugs ◽  
Infected People ◽  
Therapeutic Procedures ◽  
Viral Respiratory Infections

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is often complicated by severe acute respiratory syndrome. The new coronavirus outbreak started in China in December 2019 and rapidly spread around the world. The high diffusibility of the virus was the reason for the outbreak of the pandemic viral disease, reaching more than 100 million infected people globally by the first three months of 2021. In the various treatments used up to now, the use of antimicrobial drugs for the management, especially of bacterial co-infections, is very frequent in patients admitted to intensive care. In addition, critically ill patients with SARS-CoV-2 infection are subjected to prolonged mechanical ventilation and other therapeutic procedures often responsible for developing hospital co-infections due to multidrug-resistant bacteria. Co-infections contribute to the increase in the morbidity–mortality of viral respiratory infections. We performed this study to review the recent articles published on the antibiotic bacterial resistance and viruses to predict risk factors of coronavirus disease 2019 and to assess the multidrug resistance in patients hospitalized in the COVID-19 area.

scholarly journals Liposomes as Antibiotic Delivery Systems: A Promising Nanotechnological Strategy against Antimicrobial Resistance

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 2047
Author(s):  
Magda Ferreira ◽  
Maria Ogren ◽  
Joana N. R. Dias ◽  
Marta Silva ◽  
Solange Gil ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Private Investment ◽  
Therapeutic Index ◽  
Multidrug Resistant ◽  
Current Treatment ◽  
Delivery Systems ◽  
Resistant Bacteria ◽  
Bacterial Cells ◽  
Antimicrobial Drugs

Antimicrobial drugs are key tools to prevent and treat bacterial infections. Despite the early success of antibiotics, the current treatment of bacterial infections faces serious challenges due to the emergence and spread of resistant bacteria. Moreover, the decline of research and private investment in new antibiotics further aggravates this antibiotic crisis era. Overcoming the complexity of antimicrobial resistance must go beyond the search of new classes of antibiotics and include the development of alternative solutions. The evolution of nanomedicine has allowed the design of new drug delivery systems with improved therapeutic index for the incorporated compounds. One of the most promising strategies is their association to lipid-based delivery (nano)systems. A drug’s encapsulation in liposomes has been demonstrated to increase its accumulation at the infection site, minimizing drug toxicity and protecting the antibiotic from peripheral degradation. In addition, liposomes may be designed to fuse with bacterial cells, holding the potential to overcome antimicrobial resistance and biofilm formation and constituting a promising solution for the treatment of potential fatal multidrug-resistant bacterial infections, such as methicillin resistant Staphylococcus aureus. In this review, we aim to address the applicability of antibiotic encapsulated liposomes as an effective therapeutic strategy for bacterial infections.

scholarly journals Biofilms as Promoters of Bacterial Antibiotic Resistance and Tolerance

Antibiotics ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 3
Author(s):  
Cristina Uruén ◽  
Gema Chopo-Escuin ◽  
Jan Tommassen ◽  
Raúl C. Mainar-Jaime ◽  
Jesús Arenas
Keyword(s):  
Close Contact ◽  
Animal Health ◽  
Deep Understanding ◽  
Growth Conditions ◽  
Multidrug Resistant ◽  
Extracellular Dna ◽  
Resistant Bacteria ◽  
Resistance To Antibiotics ◽  
Global Threat ◽  
Biofilm Development

Multidrug resistant bacteria are a global threat for human and animal health. However, they are only part of the problem of antibiotic failure. Another bacterial strategy that contributes to their capacity to withstand antimicrobials is the formation of biofilms. Biofilms are associations of microorganisms embedded a self-produced extracellular matrix. They create particular environments that confer bacterial tolerance and resistance to antibiotics by different mechanisms that depend upon factors such as biofilm composition, architecture, the stage of biofilm development, and growth conditions. The biofilm structure hinders the penetration of antibiotics and may prevent the accumulation of bactericidal concentrations throughout the entire biofilm. In addition, gradients of dispersion of nutrients and oxygen within the biofilm generate different metabolic states of individual cells and favor the development of antibiotic tolerance and bacterial persistence. Furthermore, antimicrobial resistance may develop within biofilms through a variety of mechanisms. The expression of efflux pumps may be induced in various parts of the biofilm and the mutation frequency is induced, while the presence of extracellular DNA and the close contact between cells favor horizontal gene transfer. A deep understanding of the mechanisms by which biofilms cause tolerance/resistance to antibiotics helps to develop novel strategies to fight these infections.

Sign in / Sign up

Export Citation Format

Share Document