A Glycosylated Cationic Block Poly(β‐peptide) Reverses Intrinsic Antibiotic Resistance in All ESKAPE Gram‐Negative Bacteria

Si, Zhangyong; Lim, Hui Wen; Tay, Moon Y. F.; Du, Yu; Ruan, Lin; Qiu, Haofeng; Zamudio-Vázquez, Rubí; Reghu, Sheethal; Chen, Yahua; Tiong, Wen Shuo; Marimuthu, Kalisvar; De, Partha Pratim; Ng, Oon Tek; Zhu, Yabin; Gan, Yunn‐Hwen; Robin, Yonggui; Duan, Hongwei; Bazan, Guillermo C.; Greenberg, E. P.; Chan‐Park, Mary B.; Pethe, Kévin

doi:10.1002/anie.201914304

Cited by 74 publications

(52 citation statements)

References 47 publications

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“…To combat colistin resistance in bacterial pathogens, several colistin adjuvants have been discovered including antimicrobial compounds, FDA approved drugs, Eukaryotic kinase inhibitors, cationic block beta‐peptide, and small molecular compounds. [ 33–39 ] These compounds exhibited different level of synergistic effect with colistin and potentate its activity against colistin‐resistant Enterobacteriaceae. However, for most of these published compounds, they either lack in vivo efficacy data or knowledge regarding mechanism of action, hence further development of these compounds for clinical use is prohibited.…”

Section: Conclusion Remarksmentioning

confidence: 99%

Imidazole Type Antifungal Drugs Are Effective Colistin Adjuvants That Resensitize Colistin‐Resistant Enterobacteriaceae

Chen

Chan

et al. 2020

Advanced Therapeutics

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The clinical value of the last‐line antibiotic colistin is limited by its toxicity and the increasing prevalence of drug resistance in recent years. These two issues can be tackled by searching for adjuvant compounds that enhance colistin activity and facilitate reduction of treatment dosage. This study identifies a Food and Drug Administration (FDA)‐approved drug, econazole, which can act synergistically with colistin to effectively eradicate colistin‐resistant bacteria both in vitro and in a mouse infection model, and treat infections caused by colistin‐susceptible bacteria in lower doses. Structural analysis shows that econazole exhibits high lipid affinity and acts as an ionophore. Functional assays and microscopy analysis confirm that econazole causes dissipation of transmembrane proton motive force (PMF) and damage to the bacterial cell membrane. Its synergistic effect with colistin might be due to the combination of these two compounds causing further collapse of PMF, arrest of various cellular functions, and eventually cell death. These findings suggest that the econazole and colistin drug combination is highly effective in eradicating colistin‐resistant Gram negative bacterial pathogens regardless of their mechanism of colistin resistance.

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Section: Conclusion Remarksmentioning

confidence: 99%

Imidazole Type Antifungal Drugs Are Effective Colistin Adjuvants That Resensitize Colistin‐Resistant Enterobacteriaceae

Chen

Chan

et al. 2020

Advanced Therapeutics

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“…Above studies indicate that carboxylate‐initiated NCA polymerization using the terminal tetraalkylammonium carbamate as the reactive center is suitable to prepare block copolymers that have extensive applications in self‐assembly, [14, 27] antimicrobial [1i, 28] and drug delivery [29] . In a proof‐of‐concept demonstration, we did block copolymerization on BLL NCA/BLG NCA in THF using TBAA as the initiator in an open vessel at ambient condition, and easily obtained the multiblock polypeptide with 15 blocks of alternate BLL and BLG and with a narrow dispersity ( Đ =1.07–1.21) after adding each block (Figure 4 a,b).…”

Section: Resultsmentioning

confidence: 99%

Superfast and Water‐Insensitive Polymerization on α‐Amino Acid N‐Carboxyanhydrides to Prepare Polypeptides Using Tetraalkylammonium Carboxylate as the Initiator

Chen

et al. 2021

Angew Chem Int Ed

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We design the tetraalkylammonium carboxylate‐initiated superfast polymerization on α‐amino acid N‐carboxyanhydrides (NCA) for efficient synthesis of polypeptides. Carboxylates, as a new class of initiator for NCA polymerization, can initiate the superfast NCA polymerization without the need of extra catalysts and the polymerization can be operated in open vessels at ambient condition without the use of glove box. Tetraalkylammonium carboxylate‐initiated polymerization on NCA easily affords block copolymers with at least 15 blocks. Moreover, this method avoids tedious purification steps and enables direct polymerization on crude NCAs in aqueous environments to prepare polypeptides and one‐pot synthesis of polypeptide nanoparticles. These advantages and the mild polymerization condition of tetraalkylammonium carboxylate‐initiated NCA polymerization imply its great potential in functional exploration and application of polypeptides.

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“…(4) The ESKAPE family of MDR bacteria are the most notorious group of bacteria that pose a serious global health threat and account for up to 87% of all hospital acquired infections [ 40 ]. This family of bacteria has been listed as “high priority” under the WHO priority listing [ 41 – 45 ]. It is noteworthy that PDMS-PIM biomaterials could efficiently and effectively inhibit the colonization of all the members of ESKAPE group of pathogens as well as the WHO priority pathogens such MRSA and VRE .…”

Section: Discussionmentioning

confidence: 99%

Broad spectrum antimicrobial PDMS-based biomaterial for catheter fabrication

et al. 2021

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Background In addition to the widespread use of antibiotics in healthcare settings, the current COVID-19 pandemic has escalated the emergence of antibiotic resistance. Nosocomial infections among hospitalized patients is a leading site for such resistant microbial colonization due to prolonged use of invasive devices and antibiotics in therapies. Invasive medical devices, especially catheters, are prone to infections that could accelerate the development of resistant microbes. Often, catheters - particularly urinary catheters - are prone to high infection rates. Antibiotic-coated catheters can reduce infection rates and although commercially available, are limited in efficacy and choices. Methods Herein, a novel and facile method to fabricate PMDS-based biomaterial for the development of antimicrobial eluting catheters is presented. Silicone based organic polymer polydimethylsiloxane (PDMS) was used to prepare a biomaterial containing novel polymeric imidazolium antimicrobial compound. Results It was found that the PDMS-based biomaterials could eradicate microbial colonization even after 60 days in culture with continuous microbial challenge, be recycled over multiple uses, stored at room temperature for long-term usage and importantly is biocompatible. Conclusion The PDMS-based biomaterial displayed biocidal functionality on microbes of clinical origin, which form major threats in hospital acquired infections. Graphical Abstract

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A Glycosylated Cationic Block Poly(β‐peptide) Reverses Intrinsic Antibiotic Resistance in All ESKAPE Gram‐Negative Bacteria

Cited by 74 publications

References 47 publications

Imidazole Type Antifungal Drugs Are Effective Colistin Adjuvants That Resensitize Colistin‐Resistant Enterobacteriaceae

Imidazole Type Antifungal Drugs Are Effective Colistin Adjuvants That Resensitize Colistin‐Resistant Enterobacteriaceae

Superfast and Water‐Insensitive Polymerization on α‐Amino Acid N‐Carboxyanhydrides to Prepare Polypeptides Using Tetraalkylammonium Carboxylate as the Initiator

Broad spectrum antimicrobial PDMS-based biomaterial for catheter fabrication

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