Amphipathic guanidine-embedded glyoxamide-based peptidomimetics as novel antibacterial agents and biofilm disruptors

Abstract The main complications of urinary catheters are the bacteria's biofilm formation and the urinary tract infection caused by gram-positive and gram-negative bacteria. In the recent years, the attention has changed its direction toward the antimicrobial, anti-biofilmic, and hydrophobicity effects of herbal extracts. Some of these extracts can inhibit the colonization of the two bacteria Staphylococcus aureus and Escherichia coli which are resistant to antibiotics. These bacteria can stick to the surface of polymer materials due to their hydrophobicity. Thus, antibacterial hydrophilic herbal extracts are supposed to help reduce the risk of the surficial infection if they are used to impregnate the urinary catheters. In this research, the extracts of these four plants eucalyptus, rosemary, green tea and ziziphora were used as the antibacterial agents. After the impregnation and modification of the sample catheters, they were tested by AFM, FE-SEM, ATR-FTIR methods to measure their mechanical, chemical, and hydrophilic properties, during the 21-day experiment period, compared to non-impregnated ones. The tests showed the silicone catheters impregnated by the herbal extracts have some significant anti-biofilmic and antibacterial properties (P˂0.0001) due to the increase in their hydrophilic property. The impregnated catheters could be release the extracts and killed bacteria in 21 days Therefore; some herbal extracts can be good alternatives to chemical drugs.

Download Full-text

Densely Functionalized 2-methylideneazetidines: Evaluation as Antibacterials

Molecules ◽

10.3390/molecules26133891 ◽

2021 ◽

Vol 26 (13) ◽

pp. 3891

Author(s):

Giovanni Petrillo ◽

Cinzia Tavani ◽

Lara Bianchi ◽

Alice Benzi ◽

Maria Maddalena Cavalluzzi ◽

...

Keyword(s):

Antibacterial Agents ◽

Inhibitory Concentration ◽

General Procedure ◽

Eukaryotic Cells ◽

Gram Negative Bacteria ◽

Pharmacological Profile ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria ◽

Structure Activity

Twenty-two novel, variously substituted nitroazetidines were designed as both sulfonamide and urethane vinylogs possibly endowed with antimicrobial activity. The compounds under study were obtained following a general procedure recently developed, starting from 4-nitropentadienoates deriving from a common β-nitrothiophenic precursor. While being devoid of any activity against fungi and Gram-negative bacteria, most of the title compounds performed as potent antibacterial agents on Gram-positive bacteria (E. faecalis and three strains of S. aureus), with the most potent congener being the 1-(4-chlorobenzyl)-3-nitro-4-(p-tolyl)azetidine 22, which displayed potency close to that of norfloxacin, the reference antibiotic (minimum inhibitory concentration values 4 and 1–2 μg/mL, respectively). Since 22 combines a relatively efficient activity against Gram-positive bacteria and a cytotoxicity on eucharyotic cells only at 4-times higher concentrations (inhibiting concentration on 50% of the cultured eukaryotic cells: 36 ± 10 μM, MIC: 8.6 μM), it may be considered as a promising hit compound for the development of a new series of antibacterials selectively active on Gram-positive pathogens. The relatively concise synthetic route described herein, based on widely available starting materials, could feed further structure–activity relationship studies, thus allowing for the fine investigation and optimization of the toxico-pharmacological profile.

Download Full-text

γ-Alkylidene-γ-lactones and isobutylpyrrol-2(5 H )-ones analogues to rubrolides as inhibitors of biofilm formation by Gram-positive and Gram-negative bacteria

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2014.01.023 ◽

2014 ◽

Vol 24 (4) ◽

pp. 1052-1056 ◽

Cited By ~ 33

Author(s):

Ulisses A. Pereira ◽

Luiz C.A. Barbosa ◽

Célia R.A. Maltha ◽

Antônio J. Demuner ◽

Mohammed A. Masood ◽

...

Keyword(s):

Biofilm Formation ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Gram Negative

Download Full-text

Bioinspired passive anti-biofouling surfaces preventing biofilm formation

Journal of Materials Chemistry B ◽

10.1039/c4tb01522c ◽

2015 ◽

Vol 3 (7) ◽

pp. 1371-1378 ◽

Cited By ~ 36

Author(s):

Sasha Pechook ◽

Kobi Sudakov ◽

Iryna Polishchuk ◽

Ievgeniia Ostrov ◽

Varda Zakin ◽

...

Keyword(s):

Biofilm Formation ◽

Superhydrophobic Surfaces ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Gram Negative

Our bioinspired, superhydrophobic surfaces show exceptional ability to passively inhibit the biofilm formation of Gram-positive and Gram-negative bacteria over a 7 day period.

Download Full-text

Synthesis, Characterization and Antibacterial Activity Evaluation of New Indole-Based Derivatives

Iraqi Journal of Pharmaceutical Sciences ( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512) ◽

10.31351/vol29iss1pp207-2015 ◽

2020 ◽

Vol 29 (1) ◽

pp. 207-2015

Author(s):

Ahmed T. Sulaiman ◽

Susan W. Sarsam

Keyword(s):

Antibacterial Agents ◽

Glacial Acetic Acid ◽

Diffusion Method ◽

Moderate Activity ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Gram Negative ◽

Different Types ◽

Ft Ir

A new series of N-acyl hydrazones (4a-g) derived from indole-3-propionic acid (IPA) were synthesized. These N-acyl hydrazones were prepared by the reaction of 3-(1H-indol-3-yl) propane hydrazide and aldehyde in the existence of glacial acetic acid as a catalyst. 1HNMR and FT-IR analyses were used to identify the synthesized compounds and they were in vitro evaluated as antibacterial agents against six different types of microorganisms by using well diffusion method. All the tested N-acyl hydrazones (4a-g) displayed moderate activity against the Gram-negative E.coli, comparable to that of Amoxicillin. Some of the tested N-acyl hydrazones also exhibited intermediate activity against some of the examined Gram-positive and Gram-negative bacteria. While no activity was exhibited by any of the examined compounds against the Gram-positive S. aureus.

Download Full-text

Synthetic anti‐endotoxin peptides interfere with Gram‐positive and Gram‐negative bacteria, their adhesion and biofilm formation on titanium

Journal of Applied Microbiology ◽

10.1111/jam.14701 ◽

2020 ◽

Vol 129 (5) ◽

pp. 1272-1286 ◽

Cited By ~ 2

Author(s):

L. Subh ◽

W. Correa ◽

T.‐J. Pinkvos ◽

P. Behrens ◽

K. Brandenburg ◽

...

Keyword(s):

Biofilm Formation ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Gram Negative

Download Full-text

Synthesis of hierarchical CuO nanostructures: Biocompatible antibacterial agents for Gram-positive and Gram-negative bacteria

Current Applied Physics ◽

10.1016/j.cap.2016.05.006 ◽

2016 ◽

Vol 16 (8) ◽

pp. 914-921 ◽

Cited By ~ 23

Author(s):

S. Sonia ◽

R. Jayasudha ◽

Naidu Dhanpal Jayram ◽

P. Suresh Kumar ◽

D. Mangalaraj ◽

...

Keyword(s):

Antibacterial Agents ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Gram Negative

Download Full-text

Plasmids Shape the Current Prevalence of tmexCD1-toprJ1 among Klebsiella pneumoniae in Food Production Chains

mSystems ◽

10.1128/msystems.00702-21 ◽

2021 ◽

Author(s):

Kai Peng ◽

Qian Wang ◽

Yi Yin ◽

Yan Li ◽

Yuan Liu ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Human Health ◽

Food Production ◽

Antibacterial Agents ◽

Efflux Pump ◽

Multidrug Resistant ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Gram Negative ◽

Current Prevalence

Tigecycline, the first member of the glycylcycline class of antibacterial agents, is frequently used to treat complicated infections caused by multidrug-resistant Gram-positive and Gram-negative bacteria. The emergence of a novel plasmid-mediated efflux pump, TmexCD1-ToprJ1, conferring resistance to multiple antimicrobials, including tigecycline, poses a huge risk to human health.

Download Full-text

ETIOLOGICAL SIGNIFICANCE AND ANTIBIOTICOSENSETIVITY OF CERTAIN MICROORGANISMS IN AGGRAVATION OF CHRONICAL BRONCHOPULMONARY PATHOLOGY IN WORKERS OF DIVERSE ECONOMIC SECTORS

Russian Clinical Laboratory Diagnostics ◽

10.18821/0869-2084-2019-64-1-49-52 ◽

2019 ◽

Vol 64 (1) ◽

pp. 49-52

Author(s):

L. G. Gizatullina ◽

L. M. Masyagutova ◽

A. B. Bakirov

Keyword(s):

Respiratory Diseases ◽

Antibacterial Agents ◽

Intestinal Bacteria ◽

Gram Negative Bacteria ◽

Economic Sectors ◽

Gram Positive ◽

Gram Negative ◽

Upper Respiratory

It has been shown that in patients with upper respiratory diseases of occupational etiology gram negative flora prevail (38% of cases). They are followed by yeast-like fungi (up to 36% of cases), gram positive flora - 26%. The most effective antibacterial agents for treating golden staphilococcus in patients of the group studied are cefotaxime, sparfloxacine, levofloloxacine. Cefotoxime, ceftriaxon, ciprofloxacine are used against intestinal bacteria. Cefepim, ceftazidim are used against non-fermenting gram negative bacteria. C.Albicans can be treated with amfotericine and fluconazol.

Download Full-text

Outer Membrane Disruption Overcomes Intrinsic, Acquired, and Spontaneous Antibiotic Resistance

mBio ◽

10.1128/mbio.01615-20 ◽

2020 ◽

Vol 11 (5) ◽

Author(s):

Craig R. MacNair ◽

Eric D. Brown

Keyword(s):

Antibiotic Resistance ◽

Outer Membrane ◽

Biofilm Formation ◽

Antibiotic Use ◽

Membrane Disruption ◽

Permeability Barrier ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Gram Negative ◽

Outer Membrane Permeability

ABSTRACT Disruption of the outer membrane (OM) barrier allows for the entry of otherwise inactive antimicrobials into Gram-negative pathogens. Numerous efforts to implement this approach have identified a large number of OM perturbants that sensitize Gram-negative bacteria to many clinically available Gram-positive active antibiotics. However, there is a dearth of investigation into the strengths and limitations of this therapeutic strategy, with an overwhelming focus on characterization of individual potentiator molecules. Herein, we look to explore the utility of exploiting OM perturbation to sensitize Gram-negative pathogens to otherwise inactive antimicrobials. We identify the ability of OM disruption to change the rules of Gram-negative entry, overcome preexisting and spontaneous resistance, and impact biofilm formation. Disruption of the OM expands the threshold of hydrophobicity compatible with Gram-negative activity to include hydrophobic molecules. We demonstrate that while resistance to Gram-positive active antibiotics is surprisingly common in Gram-negative pathogens, OM perturbation overcomes many antibiotic inactivation determinants. Further, we find that OM perturbation reduces the rate of spontaneous resistance to rifampicin and impairs biofilm formation. Together, these data suggest that OM disruption overcomes many of the traditional hurdles encountered during antibiotic treatment and is a high priority approach for further development. IMPORTANCE The spread of antibiotic resistance is an urgent threat to global health that necessitates new therapeutics. Treatments for Gram-negative pathogens are particularly challenging to identify due to the robust outer membrane permeability barrier in these organisms. Recent discovery efforts have attempted to overcome this hurdle by disrupting the outer membrane using chemical perturbants and have yielded several new peptides and small molecules that allow the entry of otherwise inactive antimicrobials. However, a comprehensive investigation into the strengths and limitations of outer membrane perturbants as antibiotic partners is currently lacking. Herein, we interrogate the interaction between outer membrane perturbation and several common impediments to effective antibiotic use. Interestingly, we discover that outer membrane disruption is able to overcome intrinsic, spontaneous, and acquired antibiotic resistance in Gram-negative bacteria, meriting increased attention toward this approach.

Download Full-text