Emerging nanotechnologies for targeting antimicrobial resistance

Weldrick, Paul J.; Wang, Anheng; Halbus, Ahmed F.; Paunov, Vesselin N.

doi:10.1039/d1nr08157h

Cited by 34 publications

(29 citation statements)

References 159 publications

(196 reference statements)

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“…Stimuli-responsive synthetic materials, such as synthetic molecular machines, capable of providing on-site, on-demand antimicrobial action, offer the possibility of treating an infection locally with lower doses of antimicrobials, thus reducing the potential for the emergence and spread of antimicrobial resistance. [9,10,28] However, some previously described molecular machines have indiscriminate destructive capabilities and dependence on dangerous UV and near-UV wavelengths for activation. [19] In this work, several visible light-activated molecules containing a hemithioindigo core, enabling activation by visible light at 455 nm, were synthesized and screened for antibacterial activity.…”

Section: Discussionmentioning

confidence: 99%

Hemithioindigo‐Based Visible Light‐Activated Molecular Machines Kill Bacteria by Oxidative Damage

et al. 2022

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Antibiotic resistance is a growing healththreat. There is an urgent and critical need to develop new antimicrobial modalities and therapies. Here, a set of hemithioindigo (HTI)-based molecular machines capable of specifically killing Gram-positive bacteria within minutes of activation with visible light (455 nm at 65 mW cm −2 ) that are safe for mammalian cells is described. Importantly, repeated exposure of bacteria to HTI does not result in detectable development of resistance. Visible light-activated HTI kill both exponentially growing bacterial cells and antibiotic-tolerant persister cells of various Gram-positive strains, including methicillin-resistant S. aureus (MRSA). Visible light-activated HTI also eliminate biofilms of S. aureus and B. subtilis in as little as 1 h after light activation. Quantification of reactive oxygen species (ROS) formation and protein carbonyls, as well as assays with various ROS scavengers, identifies oxidative damage as the underlying mechanism for the antibacterial activity of HTI. In addition to their direct antibacterial properties, HTI synergize with conventional antibiotics in vitro and in vivo, reducing the bacterial load and mortality associated with MRSA infection in an invertebrate burn wound model. To the best of the authors' knowledge, this is the first report on the antimicrobial activity of HTI-based molecular machines.

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Section: Discussionmentioning

confidence: 99%

Hemithioindigo‐Based Visible Light‐Activated Molecular Machines Kill Bacteria by Oxidative Damage

et al. 2022

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“…It is essential to have a clear understanding of the antibacterial mechanism for developing new antibacterial materials. Compared to previous reports, this progress report concentrates on metal and metal oxide nanomaterials to summarize their anti-infective mechanism based on the components of bacteria and biofilms ( Figure 1 ) [ 21 , 22 , 23 , 24 ]. We focus on the components of bacteria (cell membrane, protein, and nucleic acid) and conclude common antibacterial mechanisms of metal and metal oxide nanomaterials.…”

Section: Introductionmentioning

confidence: 99%

Metal and Metal Oxide Nanomaterials for Fighting Planktonic Bacteria and Biofilms: A Review Emphasizing on Mechanistic Aspects

Sun

Wang

Dai

et al. 2022

IJMS

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The misuse and mismanagement of antibiotics have made the treatment of bacterial infections a challenge. This challenge is magnified when bacteria form biofilms, which can increase bacterial resistance up to 1000 times. It is desirable to develop anti-infective materials with antibacterial activity and no resistance to drugs. With the rapid development of nanotechnology, anti-infective strategies based on metal and metal oxide nanomaterials have been widely used in antibacterial and antibiofilm treatments. Here, this review expounds on the state-of-the-art applications of metal and metal oxide nanomaterials in bacterial infective diseases. A specific attention is given to the antibacterial mechanisms of metal and metal oxide nanomaterials, including disrupting cell membranes, damaging proteins, and nucleic acid. Moreover, a practical antibiofilm mechanism employing these metal and metal oxide nanomaterials is also introduced based on the composition of biofilm, including extracellular polymeric substance, quorum sensing, and bacteria. Finally, current challenges and future perspectives of metal and metal oxide nanomaterials in the anti-infective field are presented to facilitate their development and use.

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“…Recently, nanocarrier-loaded antimicrobials have shown remarkable efficiency toward bacterial and fungal pathogens in both the planktonic state − and biofilms. − Amoxicillin–clavulanic acid, also referred to as Augmentin, or amoxicillin–clavulanate (referring to the salt of clavulanic acid), was the first combination of β-lactam and β-lactamase inhibitor to be clinically used since 1981, and it still remains the only oral-use formulation available. The use of clavulanic acid in cotreatments substantially expands amoxicillin’s effectiveness, to include bacteria producing penicillinase, such as Bacteroides spp., E.…”

Section: Introductionmentioning

confidence: 99%

“…15 This has resulted in increased effectiveness of combinations of β-lactam antibiotics and clavulanic acid on β-lactam-resistant bacteria. 15 Recently, nanocarrier-loaded antimicrobials 16 have shown remarkable efficiency toward bacterial and fungal pathogens in both the planktonic state 17−21 and biofilms. 22−24 Amoxicillin− clavulanic acid, also referred to as Augmentin, or amoxicillin− clavulanate (referring to the salt of clavulanic acid), was the first combination of β-lactam and β-lactamase inhibitor to be clinically used since 1981, and it still remains the only oral-use formulation available.…”

Section: ■ Introductionmentioning

confidence: 99%

Overcoming Beta-Lactamase-Based Antimicrobial Resistance by Nanocarrier-Loaded Clavulanic Acid and Antibiotic Cotreatments

Filby

Weldrick

Paunov

2022

ACS Appl. Bio Mater.

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Antimicrobial resistance (AMR) is one of the major threats to modern healthcare. Many types of bacteria have developed resistance to multiple antibiotic treatments, while additional antibiotics have not been recently brought to market. One approach to counter AMR based on the beta-lactamase enzyme has been to use cotreatments of an antibiotic and an inhibitor, to enhance the antibiotic action. Here, we aimed to enhance this technique by developing nanocarriers of two cationic beta-lactam class antibiotics, amoxicillin, and ticarcillin, combined with a beta-lactamase inhibitor, clavulanic acid, which can potentially overcome this type of AMR. We demonstrate for the first time that beta-lactamase inhibitor-loaded nanocarriers in cotreatments with either free or nanocarrier-loaded beta-lactam antibiotics can enhance their effectiveness further than when used alone. We use surfacefunctionalized shellac-/Poloxamer 407-stabilized antibiotic nanocarriers on Pseudomonas aeruginosa, which is susceptible to ticarcillin but is resistant to amoxicillin. We show an amplification of the antibiotic effect of amoxicillin and ticarcillin loaded in shellac nanoparticles, both alone and as a cotreatment with free or nanocarrier-loaded clavulanic acid. We also report a significant increase in the antimicrobial effects of clavulanic acid loaded in such nanocarriers as a cotreatment. We explain the increased antimicrobial activity of the cationically functionalized antibiotic-loaded nanoparticles with electrostatic attraction to the bacterial cell wall, which delivers higher local antibiotic and inhibitor concentrations. The effect is due to the accumulation of the clavulanic acid-loaded nanocarriers on the bacterial cell walls that allows a higher proportion of the inhibitor to engage with the produced intracellular betalactamases. These nanocarriers were also found to have a very low cytotoxic effect against human keratinocytes, which shows great potential for overcoming enzyme-based AMR.

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Emerging nanotechnologies for targeting antimicrobial resistance

Abstract: We review recently developed advanced nanotechnologies for overcoming antimicrobial resistance and tackling of biofilm infections.

Cited by 34 publications

References 159 publications

Hemithioindigo‐Based Visible Light‐Activated Molecular Machines Kill Bacteria by Oxidative Damage

Hemithioindigo‐Based Visible Light‐Activated Molecular Machines Kill Bacteria by Oxidative Damage

Metal and Metal Oxide Nanomaterials for Fighting Planktonic Bacteria and Biofilms: A Review Emphasizing on Mechanistic Aspects

Overcoming Beta-Lactamase-Based Antimicrobial Resistance by Nanocarrier-Loaded Clavulanic Acid and Antibiotic Cotreatments

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