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Nanomaterial-based therapeutics for antibiotic-resistant bacterial infections

Nature Reviews Microbiology volume 19, pages 23–36 (2021)Cite this article

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Abstract

Antibiotic-resistant bacterial infections arising from acquired resistance and/or through biofilm formation necessitate the development of innovative ‘outside of the box’ therapeutics. Nanomaterial-based therapies are promising tools to combat bacterial infections that are difficult to treat, featuring the capacity to evade existing mechanisms associated with acquired drug resistance. In addition, the unique size and physical properties of nanomaterials give them the capability to target biofilms, overcoming recalcitrant infections. In this Review, we highlight the general mechanisms by which nanomaterials can be used to target bacterial infections associated with acquired antibiotic resistance and biofilms. We emphasize design elements and properties of nanomaterials that can be engineered to enhance potency. Lastly, we present recent progress and remaining challenges for widespread clinical implementation of nanomaterials as antimicrobial therapeutics.

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Fig. 1: Nano versus micro — antimicrobial mechanisms of nanomaterials.
Fig. 2: Examples of nanomaterial-based strategies used to combat bacterial infections.
Fig. 3: Eradicating biofilms using nanoparticles.

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Acknowledgements

This research was supported by the US National Institutes of Health (AI134770).

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Authors and Affiliations

  1. Department of Chemistry, University of Massachusetts Amherst, Amherst, MA, USA

    Jessa Marie V. Makabenta, Ahmed Nabawy, Cheng-Hsuan Li & Vincent M. Rotello

  2. Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    Suzannah Schmidt-Malan & Robin Patel

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The authors contributed equally to all aspects of the article.

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Correspondence to Vincent M. Rotello.

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Competing interests

R.P. reports grants from CD Diagnostics, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, ContraFect, TenNor Therapeutics Limited and Shionogi. R.P. is a consultant to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics and Qvella; monies are paid to Mayo Clinic. In addition, R.P. has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic and a patent on an antibiofilm substance issued. R.P. receives travel reimbursement from the American Society for Microbiology (ASM) and the Infectious Disease Society of America (IDSA), an editor’s stipend from IDSA and honoraria from NBME, Up-to-Date and the Infectious Diseases Board Review Course. All other authors declare no competing interests.

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Glossary

Osteomyelitis

Bone infection.

Infective endocarditis

Infection of endocardium, typically of heart valves.

Persister cells

Subpopulation of dormant, antibiotic-tolerant bacterial cells that are able to resume growth after antimicrobial stress is relieved.

Debridement

Surgical removal of damaged or dead tissue from an infected wound.

Nanocarriers

A drug delivery platform in the nanoscale range (2–500 nm). Common nanocarriers include liposomes, polymers and micelles.

Fenton-inactive metals

Also called ‘redox-inactive metals’, these are a class of transition metals (such as Ag and Hg) that cannot undergo redox reaction and hence cannot inherently produce toxic reactive oxygen species.

Peritonitis

Inflammation of the peritoneum, the tissue layer lining the inner wall of the abdomen, often as a result of bacterial infection.

Chitosan

A linear polysaccharide, obtained from the outer skeleton of insects and shellfish, composed of randomly distributed d-glucosamine and N-acetyl-d-glucosamine units.

Therapeutic index

A quantitative measure of the relative safety of a drug determined by the dosage that produces a therapeutic effect without host toxicity and the concentration that results in dangerous side effects.

Quorum sensing

A process whereby bacteria communicate and perform coordinated activities in response to a particular cell population density determined by specific signalling molecules.

Cypate

A near-infrared fluorescent dye belonging to the carbocyanine dye family, widely used for metabolite labelling and in vivo imaging.

Proline

A proteinogenic amino acid vital for the biosynthesis of collagen.

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Makabenta, J.M.V., Nabawy, A., Li, CH. et al. Nanomaterial-based therapeutics for antibiotic-resistant bacterial infections. Nat Rev Microbiol 19, 23–36 (2021). https://doi.org/10.1038/s41579-020-0420-1

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