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Abstract The failure to treat everyday bacterial infections is a current threat as pathogens are finding new ways to thwart antibiotics through mechanisms of resistance and intracellular refuge, thus rendering current antibiotic strategies ineffective. Cell‐penetrating peptides (CPPs) are providing a means to improve antibiotics that are already approved for use. Through coadministration and conjugation of antibiotics with CPPs, improved accumulation and selectivity with alternative and/or additional modes of action against infections have been observed. Herein, we review the recent progress of this antibiotic–cell‐penetrating peptide strategy in combatting sensitive and drug‐resistant pathogens. We take a closer look into the specific antibiotics that have been enhanced, and in some cases repurposed as broad‐spectrum drugs. Through the addition and conjugation of cell‐penetrating peptides to antibiotics, increased permeation across mammalian and/or bacterial membranes and a broader range in bacterial selectivity have been achieved.
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This content will become publicly available on June 1, 2026
Novel Approaches for Treatment of Intraoral Microbial Infections
Historically, broad-spectrum antibiotics have represented a major component of the therapeutic armamentarium used to treat common oral diseases associated with a bacterial etiology. The fact that these diseases are due to the accumulation of multispecies biofilms composed of ever-increasing numbers of resistant organisms has dramatically affected the efficacy of many of these drugs. Furthermore, it is now appreciated that repeated use of broad-spectrum antibiotics also affects the composition of the host commensal microbiota, which can have both local and systemic implications. In recognition of the limitations of classical antibiotics, alternative chemical, physical, and mechanical strategies are either in use or development. These include novel narrow-spectrum antimicrobials such as antitoxins, bacteriophages, and antibody-conjugated drugs that can target specific microbes while minimizing the emergence of resistant organisms and preserving eubiotic microbes. Other approaches, such as new broad-spectrum non-antibiotic strategies and probiotics, are aimed at disrupting or altering the composition of oral biofilms and their extracellular matrices to facilitate the elimination of overt pathogens by the host response and/or adjunctive antimicrobials. This critical review describes the use and limitations of broad- and narrow-spectrum strategies currently being used to treat common bacterially induced oral diseases as well as alternative methods in development.
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- PAR ID:
- 10630417
- Publisher / Repository:
- Sage
- Date Published:
- Journal Name:
- Journal of Dental Research
- Volume:
- 104
- Issue:
- 6
- ISSN:
- 0022-0345
- Page Range / eLocation ID:
- 584 to 593
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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