Polysaccharide-capped silver Nanoparticles inhibit biofilm formation and eliminate multi-drug-resistant bacteria by disrupting bacterial cytoskeleton with reduced cytotoxicity towards mammalian cells

Bacterial biofilms formed through secretion of extracellular polymeric substances (EPS) have been implicated in many serious infections and can increase antibiotic resistance by a factor of more than 1000.

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An unexpected discovery toward novel membrane active sulfonyl thiazoles as potential MRSA DNA intercalators

Future Medicinal Chemistry ◽

10.4155/fmc-2019-0303 ◽

2020 ◽

Vol 12 (19) ◽

pp. 1709-1727 ◽

Cited By ~ 1

Author(s):

Yuan-Yuan Hu ◽

Juan Wang ◽

Tie-Jun Li ◽

Rammohan R Yadav Bheemanaboina ◽

Mohammad Fawad Ansari ◽

...

Keyword(s):

Mammalian Cells ◽

Antibacterial Agents ◽

Antimicrobial Agents ◽

Methicillin Resistant Staphylococcus Aureus ◽

Inhibitory Concentration ◽

Resistant Bacteria ◽

Drug Resistant ◽

Dna Intercalators ◽

Dna Targeting ◽

Drug Resistant Bacteria

Aim: With the increasing emergence of drug-resistant bacteria, the need for new antimicrobial agents has become extremely urgent. This work was to develop sulfonyl thiazoles as potential antibacterial agents. Results & methodology: Novel hybrids of sulfonyl thiazoles were developed from commercial acetanilide and acetylthiazole. Hybrids 6e and 6f displayed excellent inhibitory efficacy against clinical methicillin-resistant Staphylococcus aureus (MRSA) (minimum inhibitory concentration = 1 μg/ml) without obvious toxicity toward normal mammalian cells (RAW 264.7). The combination uses were found to improve the antimicrobial ability. Further preliminary antibacterial mechanism experiments showed that the active molecule 6f could effectively interfere with MRSA membrane and insert into MRSA DNA. Conclusion: Compounds 6e and 6f could serve as potential DNA-targeting templates toward the development of promising antimicrobial agents.

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Xenopus laevis oocytes infected with multi-drug–resistant bacteria: implications for electrical recordings

The Journal of General Physiology ◽

10.1085/jgp.201110661 ◽

2011 ◽

Vol 138 (2) ◽

pp. 271-277 ◽

Cited By ~ 9

Author(s):

Denice O'Connell ◽

Karen Mruk ◽

Jessica M. Rocheleau ◽

William R. Kobertz

Keyword(s):

Xenopus Laevis ◽

Mammalian Cells ◽

Resistant Bacteria ◽

Xenopus Laevis Oocytes ◽

Xenopus Laevis Oocyte ◽

Drug Resistant ◽

Animal Pole ◽

Antibiotic Cocktail ◽

Storage Media ◽

Drug Resistant Bacteria

The Xenopus laevis oocyte has been the workhorse for the investigation of ion transport proteins. These large cells have spawned a multitude of novel techniques that are unfathomable in mammalian cells, yet the fickleness of the oocyte has driven many researchers to use other membrane protein expression systems. Here, we show that some colonies of Xenopus laevis are infected with three multi-drug–resistant bacteria: Pseudomonas fluorescens, Pseudomonas putida, and Stenotrophomonas maltophilia. Oocytes extracted from infected frogs quickly (3–4 d) develop multiple black foci on the animal pole, similar to microinjection scars, which render the extracted eggs useless for electrical recordings. Although multi-drug resistant, the bacteria were susceptible to amikacin and ciprofloxacin in growth assays. Supplementing the oocyte storage media with these two antibiotics prevented the appearance of the black foci and afforded oocytes suitable for whole-cell recordings. Given that P. fluorescens associated with X. laevis has become rapidly drug resistant, it is imperative that researchers store the extracted oocytes in the antibiotic cocktail and not treat the animals harboring the multi-drug–resistant bacteria.

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Antibacterial Effects of Quinazolin-4(3H)-One Functionalized-Conjugated Silver Nanoparticles

Antibiotics ◽

10.3390/antibiotics8040179 ◽

2019 ◽

Vol 8 (4) ◽

pp. 179 ◽

Cited By ~ 1

Author(s):

Abdulkader Masri ◽

Ayaz Anwar ◽

Naveed Ahmed Khan ◽

Muhammad Saquib Shahbaz ◽

Khalid Mohammed Khan ◽

...

Keyword(s):

Silver Nanoparticles ◽

Resistant Bacteria ◽

Drug Resistant ◽

One Pot ◽

Benzoic Acid Derivatives ◽

Drug Resistant Bacteria ◽

Resonance Band ◽

Ft Ir ◽

Ir Study ◽

Functionally Diverse

Infections due to multi-drug resistant bacteria are on the rise and there is an urgent need to develop new antibacterials. In this regard, a series of six functionally diverse new quinazolinone compounds were synthesized by a facile one-pot reaction of benzoic acid derivatives, trimethoxymethane and aniline derivatives. Three compounds of 3-aryl-8-methylquinazolin-4(3H)-one, and 3-aryl-6,7-dimethoxyquinazolin4(3H)-one were prepared and tested against multi-drug resistant bacteria. Furthermore, we determined whether conjugation with silver nanoparticles improved the antibacterial efficacy of these quinazolinone derivatives. The newly synthesized compounds were characterized by ultraviolet visible spectrophotometry (UV-vis), Zetasizer analysis, Fourier transform infrared spectroscopic methods (FT-IR), and scanning electron microscopy (SEM). Using bactericidal evaluation, effects were determined against selected Gram-negative and Gram-positive bacteria. Furthermore, cytotoxicity of nanoconjugates on human cells were determined. The UV-vis spectrum of silver nanoparticles conjugated quinazolinone displayed surface plasmon resonance band in the range of 400–470 nm, and the size of nanoparticles was detected to be in the range of 100–250 nm by dynamic light scattering (DLS). FT-IR study confirmed the stabilization of silver nanoparticles by the presence of diverse functional arayl on each compound. SEM further revealed the construction of spherical nanoparticles. Among the quinazolinone derivative tested, two compounds (QNZ 4, QNZ 6) conjugated with silver nanoparticles showed enhanced antibacterial activity against Escherichia coli K1, Streptococcus pyogenes, Klebsiella pneumoniae, B. cereus and P. aeruginosa as compared to the compounds.

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AIE-Active Poly(phenyleneethynylene)s for Fluorescence and Raman Dual-Modal Imaging and Drug-Resistant Bacteria Killing

10.26434/chemrxiv.14776893 ◽

2021 ◽

Author(s):

xiang su ◽

ruihua liu ◽

Ying Li ◽

Ting Han ◽

Zhijun Zhang ◽

...

Keyword(s):

Self Assembly ◽

Mammalian Cells ◽

Antibacterial Activities ◽

Resistant Bacteria ◽

Drug Resistant ◽

Organic Optoelectronics ◽

Drug Resistant Bacteria ◽

Fluorescence Efficiency ◽

Alkyl Side Chains ◽

Bacteria Killing

Poly(phenyleneethynylene) (PPE) is a widely used functional conjugated polymer with applications ranging from organic optoelectronics and fluorescence sensors to optical imaging and theranostics. However, the fluorescence efficiency of PPE in aggregate states is generally not as good as their solution states, which greatly compromises their performance in fluorescence-related applications. Herein, we design and synthesize a series of PPE derivatives with typical aggregation-induced emission (AIE) properties. In these PPEs, the diethylamino-substituted tetraphenylethene units function as the long-wavelength AIE source and the alkyl side chains serve as the functionalization site. The obtained AIE-active PPEs with large π-conjugation show strong aggregate-state fluorescence, interesting self-assembly behaviors, inherently enhanced alkyne vibrations in the Raman-silent region of cells, and efficient antibacterial activities. The PPE nanoparticles with good cellular uptake capability can clearly and sensitively visualize the tumor region and residual tumors via their fluorescence and Raman signals, respectively, to benefit the precise tumor surgery. After post-functionalization, the obtained PPE-based polyelectrolyte can preferentially image bacteria over mammalian cells and possesses efficient photodynamic killing capability against Gram-positive and drug-resistant bacteria. This work provides a feasible design strategy for developing multifunctional conjugated polymers with multimodal imaging capability as well as photodynamic antimicrobial ability.

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The Potential of Modified and Multimeric Antimicrobial Peptide Materials as Superbug Killers

Frontiers in Chemistry ◽

10.3389/fchem.2021.795433 ◽

2022 ◽

Vol 9 ◽

Author(s):

Tamara Matthyssen ◽

Wenyi Li ◽

James A. Holden ◽

Jason C. Lenzo ◽

Sara Hadjigol ◽

...

Keyword(s):

Self Assembly ◽

Mammalian Cells ◽

Side Chain ◽

Resistant Bacteria ◽

Amino Acid Side Chain ◽

Drug Resistant ◽

Physiological Conditions ◽

Drug Resistant Bacteria ◽

Peptide Materials ◽

Living Organisms

Antimicrobial peptides (AMPs) are found in nearly all living organisms, show broad spectrum antibacterial activity, and can modulate the immune system. Furthermore, they have a very low level of resistance induction in bacteria, which makes them an ideal target for drug development and for targeting multi-drug resistant bacteria ‘Superbugs’. Despite this promise, AMP therapeutic use is hampered as typically they are toxic to mammalian cells, less active under physiological conditions and are susceptible to proteolytic degradation. Research has focused on addressing these limitations by modifying natural AMP sequences by including e.g., d-amino acids and N-terminal and amino acid side chain modifications to alter structure, hydrophobicity, amphipathicity, and charge of the AMP to improve antimicrobial activity and specificity and at the same time reduce mammalian cell toxicity. Recently, multimerisation (dimers, oligomer conjugates, dendrimers, polymers and self-assembly) of natural and modified AMPs has further been used to address these limitations and has created compounds that have improved activity and biocompatibility compared to their linear counterparts. This review investigates how modifying and multimerising AMPs impacts their activity against bacteria in planktonic and biofilm states of growth.

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Synthesis of silver nanoparticles using Nigella sativa seed extracts and assessment of their antibacterial activity

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i2.2248 ◽

2020 ◽

Vol 11 (2) ◽

pp. 2525-2532

Author(s):

Sheik Shehensha ◽

Jyothi M V

Keyword(s):

Silver Nanoparticles ◽

Antibacterial Activity ◽

Streptococcus Pyogenes ◽

Nigella Sativa ◽

Resistant Bacteria ◽

Drug Resistant ◽

Drug Resistant Bacteria ◽

Resistant Strains ◽

Nigella Sativa Seed ◽

Seed Extracts

Silver nanoparticles were biosynthesized from Nigella sativa seed extracts using ethanol and chloroform. The antibacterial activity of silver nanoparticles against some drug-resistant bacteria has been established, but further study is needed to assess whether these particles could be an option for the treatment and prevention of drug-resistant microbial infections. Synthesized nanoparticles were characterized and screened for their antibacterial properties on resistant strains. The biosynthesized silver nanoparticles were characterized by UV-Visible, FTIR, Dynamic light scattering and Scanning Electron Microscope (SEM) analysis. The antibacterial action of biosynthesized silver nanoparticles was assessed by Microtitre Broth dilution process using Ciprofloxacin as standard, against resistant strains like Pseudomonas aeruginosa, Clostridium difficile, Klebsiella pneumoniae and Streptococcus pyogenes. The Silver nanoparticles obtained from chloroform extract of Nigella sativa seeds were more effective against Pseudomonas aeuruginosa, Clostridium difficile and Streptococcus pyogenes; than ethanolic seed extracts at 120 µL. Our data propose that the silver nanoparticles are effective against a variety of drug-resistant bacteria, which makes them a potential candidate for use in pharmaceutical products that may help to treat drug-resistant pathogens in different clinical environments. The present study focuses on the ability of phytoconstituents capped with silver nitrate can be used to treat infections caused by resistant bacteria

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Conjugation of Silver Nanoparticles with De Novo Engineered Cationic Antimicrobial Peptides: Proposal for Study (Preprint)

10.2196/preprints.28307 ◽

2021 ◽

Author(s):

Alvin Hu

Keyword(s):

Antimicrobial Activity ◽

Silver Nanoparticles ◽

Minimum Inhibitory Concentration ◽

Antimicrobial Peptides ◽

Inhibitory Concentration ◽

De Novo ◽

Resistant Bacteria ◽

Drug Resistant ◽

Cationic Antimicrobial Peptides ◽

Drug Resistant Bacteria

BACKGROUND Cationic antimicrobial peptides have broad antimicrobial activity and provide a novel way of targeting multi drug resistant bacteria in an era of increasing antimicrobial resistance. Current developments show positive prospects for both antimicrobial peptides and silver nanoparticles individually. OBJECTIVE The primary objective is to propose another method of enhancing antimicrobial activity by conjugating silver nanoparticles with cationic antimicrobial peptides for a subsequent preliminary assessment on studying the minimum inhibitory concentration of multi drug resistant bacteria. The secondary objective would be to evaluate the safety of the conjugated compound to assess viability for in vivo use. METHODS The proposition is planned for approximately 3 overarching stages. Firstly, I propose synthesis of wlbu2c, a modified version of antimicrobial peptide wlbu2 with an added cysteine group, using standard Fmoc procedure. This will subsequently be attempted to stably conjugate with silver nanoparticles ideally through photochemical means. Secondly, the conjugate wlbu2c-AgNP will be tested for antimicrobial activity following Clinical & Laboratory Standards Institute Manual on standard minimum inhibitory concentration testing. If all of the above is completed the experiment can progress to the assessment of cytotoxicity using cell lysis assays. RESULTS I-TASSER simulation revealed that our modified peptide wlbu2c has similar secondary structure to original wlbu2 peptide. No other results have been obtained at this time other than aforementioned theoretical propositions. CONCLUSIONS The addition of silver nanoparticles to already developing de novo engineered antimicrobial peptides provide a second degree of freedom toward the development of potent antimicrobials. Future prospects include emergency last line therapy, treatment for current difficult to eradicate bacterial colonization such as in cystic fibrosis, implantable medical devices, cancer and immunotherapy. This proposal is intended to be provided to the public as I do not anticipate funding at this time.

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Biotechnological War against Biofilms. Could Phages Mean the End of Device-Related Infections?

The International Journal of Artificial Organs ◽

10.1177/039139880703000910 ◽

2007 ◽

Vol 30 (9) ◽

pp. 805-812 ◽

Cited By ~ 8

Author(s):

J.L. Del Pozo ◽

M. Alonso ◽

C.R. Arciola ◽

R. Gonzalez ◽

J. Leiva ◽

...

Keyword(s):

Clinical Practice ◽

Biofilm Formation ◽

Therapeutic Agents ◽

Antibiotic Activity ◽

Therapeutic Use ◽

Resistant Bacteria ◽

Clinical Settings ◽

Drug Resistant ◽

Drug Resistant Bacteria ◽

Great Prevalence

Microorganisms universally attach to surfaces, resulting in biofilm formation. These biofilms entail a serious problem in daily clinical practice because of the great prevalence of implantable device-related infections. Differences in antibiotic activity against planktonic and sessile bacteria may relate to clinical failures in the treatment of biofilm-related infections (BRI). Bacteriophages have several characteristics that make them potentially attractive therapeutic agents in some selected clinical settings, like for example BRI. They are highly specific and very effective in lysing targeted bacteria, moreover, they appear to be safe for humans. Many studies have shown the potential of phages for the treatment of infectious diseases in plants and animals, including infections with highly drug-resistant bacteria. The therapeutic use of bacteriophages, possibly in combination with antibiotics, may be a valuable approach in BRI. However, many important questions still remain that must be addressed before phages can be endorsed for therapeutic use in humans.

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