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

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.

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

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.

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

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.

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

2020 ◽  
Vol 12 (19) ◽  
pp. 1709-1727 ◽  
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.

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

2011 ◽  
Vol 138 (2) ◽  
pp. 271-277 ◽  
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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