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Review
. 2025 Sep 18:16:1625300.
doi: 10.3389/fmicb.2025.1625300. eCollection 2025.

Development of polymyxin- and aminoglycoside-based outer membrane permeabilizers: a review

Danzel Marie Ramirez  1 , Frank Schweizer  1   2
Affiliations
Review

Development of polymyxin- and aminoglycoside-based outer membrane permeabilizers: a review

Danzel Marie Ramirez et al. Front Microbiol. .

Abstract

The prevalence of antimicrobial resistance (AMR) necessitates the development of alternative therapeutic options, particularly against critical priority Gram-negative pathogens. The utilization of antibiotic adjuvants or potentiators is an advantageous strategy that targets bacterial resistance mechanisms, thereby augmenting the activity of an antibiotic used in combination. Among these, outer membrane (OM) permeabilizers are a promising class of adjuvants which compromise the OM barrier unique to Gram-negative bacteria. This review focuses on the emerging role of polymyxins and aminoglycosides - two structurally distinct antibiotics with different modes of action, but share the ability to interact with the bacterial OM. Here, we explore the design, modification, and application of polymyxin- and aminoglycoside-based OM permeabilizers, highlighting their potential against resistant Gram-negative infections.

Keywords: aminoglycosides; antibiotic adjuvants; combination therapy; outer membrane permeabilizers; polymyxins; potentiators.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Outer membrane of Gram-negative bacteria.
Figure 2
Figure 2
Structures of polymyxins and their derivatives.
Figure 3
Figure 3
Structures of polymyxin hybrids.
Figure 4
Figure 4
Structures of different aminoglycosides.
Figure 5
Figure 5
Structures of tobramycin and nebramine-based hybrids, homodimers, chimeric and trimeric molecules.
Figure 6
Figure 6
Structures of amphiphilic tobramycin derivatives.
See this image and copyright information in PMC

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