Synergism between Rifampicin and Cationic Polyurethanes Overcomes Intrinsic Resistance of <i>Escherichia coli</i>

Tantisuwanno, Chinnapatch; Dang, Francis; Bender, Kristin; Spencer, John David; Jennings, Matthew E.; Barton, Hazel A.; Joy, Abraham

doi:10.1021/acs.biomac.1c00306

Cited by 17 publications

(13 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…256,258 Given the inclusion criteria noted in the introduction, only small-molecule synergists (MW under 1500 kDa) are included in this Review, and as such we do not discuss larger polycationic polymers even though some have been shown to exhibit synergistic activity. [90][91][92][93][94][95][96]259,260 It is noteworthy, however, that branched polyethylenimine (BPEI) with a MW of 600 Da shows synergistic activity (Figure 7G, Table 5) and can also eradicate biofilms when co-administered with a variety of antibiotics. 261 Mechanistic studies using isothermal titration calorimetry and fluorescence spectroscopy indicate that, at the concentration required for antibiotic potentiation, 600 Da BPEI reduces diffusion barriers from LPS without disrupting the OM itself.…”

Section: Synergists Based On Approved Drugsmentioning

confidence: 99%

“…The scope of the synergists included in this Review ranges from peptides to synthetic small molecules and small polymers of <1500 Da. In this regard, protein-based OM disrupters such as the membrane attack complex (MAC), lactoferrin, and the bactericidal/permeability-increasing protein (BPI) or larger polymers or polymer-like agents − will not be discussed. This Review is further organized on the basis of the chemical families of the synergists covered.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Synergy by Perturbing the Gram-Negative Outer Membrane: Opening the Door for Gram-Positive Specific Antibiotics

Wesseling

Martin

2022

ACS Infect. Dis.

View full text Add to dashboard Cite

New approaches to target antibacterial agents toward Gram-negative bacteria are key, given the rise of antibiotic resistance. Since the discovery of polymyxin B nonapeptide as a potent Gram-negative outer membrane (OM)-permeabilizing synergist in the early 1980s, a vast amount of literature on such synergists has been published. This Review addresses a range of peptide-based and small organic compounds that disrupt the OM to elicit a synergistic effect with antibiotics that are otherwise inactive toward Gram-negative bacteria, with synergy defined as a fractional inhibitory concentration index (FICI) of <0.5. Another requirement for the inclusion of the synergists here covered is their potentiation of a specific set of clinically used antibiotics: erythromycin, rifampicin, novobiocin, or vancomycin. In addition, we have focused on those synergists with reported activity against Gram-negative members of the ESKAPE family of pathogens namely, Escherichia coli , Pseudomonas aeruginosa , Klebsiella pneumoniae , and/or Acinetobacter baumannii . In cases where the FICI values were not directly reported in the primary literature but could be calculated from the published data, we have done so, allowing for more direct comparison of potency with other synergists. We also address the hemolytic activity of the various OM-disrupting synergists reported in the literature, an effect that is often downplayed but is of key importance in assessing the selectivity of such compounds for Gram-negative bacteria.

show abstract

Section: Synergists Based On Approved Drugsmentioning

confidence: 99%

mentioning

confidence: 99%

Synergy by Perturbing the Gram-Negative Outer Membrane: Opening the Door for Gram-Positive Specific Antibiotics

Wesseling

Martin

2022

ACS Infect. Dis.

View full text Add to dashboard Cite

show abstract

“…Tantisuwanno et al 167 prepared the cationic PU using 1,6-hexamethylene diisocyanate (HDI) and N-functionalized diethanolamines. The cationic PU exhibited the synergistic effect with rifampicin, a polyketide that would otherwise be excluded by the outer membrane of Gram-negative bacteria, on different strains of E. coli.…”

Section: Quaternary Ammonium Salts-and Zwitterions-based Polyurethane...mentioning

confidence: 99%

Polyurethane‐basedcomposites with promising antibacterial properties

Kasi

Sathishkumar

Zhang

et al. 2022

J of Applied Polymer Sci

View full text Add to dashboard Cite

Polyurethane (PU) is a well-known synthetic polymer consisting of isocyanates, polyols, and chain extenders. The incorporation of fillers into the PU polymeric matrix, including inorganic nanomaterials, synthetic polymers, natural components, quaternary ammonium salts, and commercial drugs, bestows the endproducts with unique and improved physicochemical properties. Fillers can be used to tailor the molecular orientation, crystallinity, cross-linking, and functional chemical groups of PU-based composites. The bactericidal ability of PU composites highly depends on their surface composition, morphology, charge, and stability. Recent advancements highlight the potential of PU composites in combating bacterial infections. In this review, the cutting-edge of inorganic and organicbased PU composites for antibacterial applications is addressed. Notably, selective examples of scientific reports' key findings and their crucial information on PU composites are discussed. Furthermore, the positive impact of PU composites on the future prospects of this field is explored. This review comprehensively deliberates the values of PU composites towards practical applications in the biomedical field of antibacterial activity. This review can help researchers to gain widespread knowledge and a better understanding of PU composites for antibacterial applications.

show abstract

“…Previous efforts in the search for compounds capable of sensitizing Gram-negative bacteria have focused on using polycationic peptides such as colistin and its analogues such as polymyxin B nonapeptide (PMBN) with very promising results. ,,− Recently, a linear antibacterial peptide was identified as a broad-spectrum antibiotic adjuvant . Similarly, cationic polymers have been shown to sensitize Gram-negative bacteria toward antibiotics. − Recently, an FDA-approved antifungal drug, pentamidine (NebuPent as the isethionate salt), was reported as a non-polypeptide sensitizer of Gram-negative bacteria including drug-resistant strains, with the ability to sensitize by ∼30-fold at the dosage of ∼50 μg/mL . Pentamidine disrupts bacterial OM by binding to lipopolysaccharide (LPS).…”

Section: Introductionmentioning

confidence: 99%

Restoring and Enhancing the Potency of Existing Antibiotics against Drug-Resistant Gram-Negative Bacteria through the Development of Potent Small-Molecule Adjuvants

Choudhury

Yang

et al. 2022

ACS Infect. Dis.

View full text Add to dashboard Cite

The rapid and persistent emergence of drug-resistant bacteria poses a looming public health crisis. The possible task of developing new sets of antibiotics to replenish the existing ones is daunting to say the least. Searching for adjuvants that restore or even enhance the potency of existing antibiotics against drug-resistant strains of bacteria represents a practical and cost-effective approach. Herein, we describe the discovery of potent adjuvants that extend the antimicrobial spectrum of existing antibiotics and restore their effectiveness toward drug-resistant strains including mcr-1-expressing strains. From a library of cationic compounds, MD-100, which has a diamidine core structure, was identified as a potent antibiotic adjuvant against Gram-negative bacteria. Further optimization efforts including the synthesis of ∼20 compounds through medicinal chemistry work led to the discovery of a much more potent compound MD-124. MD-124 was shown to sensitize various Gram-negative bacterial species and strains, including multidrug resistant pathogens, toward existing antibiotics with diverse mechanisms of action. We further demonstrated the efficacy of MD-124 in an ex vivo skin infection model and in an in vivo murine systemic infection model using both wild-type and drug-resistant Escherichia coli strains. MD-124 functions through selective permeabilization of the outer membrane of Gram-negative bacteria. Importantly, bacteria exhibited low-resistance frequency toward MD-124. In-depth computational investigations of MD-124 binding to the bacterial outer membrane using equilibrium and steered molecular dynamics simulations revealed key structural features for favorable interactions. The very potent nature of such adjuvants distinguishes them as very useful leads for future drug development in combating bacterial drug resistance.

show abstract

Synergism between Rifampicin and Cationic Polyurethanes Overcomes Intrinsic Resistance of Escherichia coli

Cited by 17 publications

References 57 publications

Synergy by Perturbing the Gram-Negative Outer Membrane: Opening the Door for Gram-Positive Specific Antibiotics

Synergy by Perturbing the Gram-Negative Outer Membrane: Opening the Door for Gram-Positive Specific Antibiotics

Polyurethane‐basedcomposites with promising antibacterial properties

Restoring and Enhancing the Potency of Existing Antibiotics against Drug-Resistant Gram-Negative Bacteria through the Development of Potent Small-Molecule Adjuvants

Contact Info

Product

Resources

About