Abstract

Antimicrobial resistance is a significant threat to human health worldwide, forcing scientists to explore non-traditional antibacterial agents to support rapid interventions and combat the emergence and spread of drug resistant bacteria. Many new antibiotic-free approaches are being developed while the old ones are being revised, resulting in creating unique solutions that arise at the interface of physics, nanotechnology, and microbiology. Specifically, physical factors (e.g., pressure, temperature, UV light) are increasingly used for industrial sterilization. Nanoparticles (unmodified or in combination with toxic compounds) are also applied to circumvent in vivo drug resistance mechanisms in bacteria. Recently, bacteriophage-based treatments are also gaining momentum due to their high bactericidal activity and specificity. Although the number of novel approaches for tackling the antimicrobial resistance crisis is snowballing, it is still unclear if any proposed solutions would provide a long-term remedy. This review aims to provide a detailed overview of how bacteria acquire resistance against these non-antibiotic factors. We also discuss innate bacterial defense systems and how bacteriophages have evolved to tackle them.

Highlights

  • The last decade has shown that antibiotic resistance is one of the most pressing issues in the healthcare system, causing a financial burden on hospitals and societies due to the prolongation of illness and subsequent treatment [1]

  • New strains of superbugs are discovered at an alarming rate due to human negligence of antibiotics and acquisition of new mutations leading to rapidly evolving bacterial strains [3,4]

  • Deinococcus swuensi is an example of a highly resistant strain, which shows a unique landscape of differentially expressed genes that distinctly determine resistance to UV radiation compared to commonly observed mechanisms [41]

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Summary

Introduction

The last decade has shown that antibiotic resistance is one of the most pressing issues in the healthcare system, causing a financial burden on hospitals and societies due to the prolongation of illness and subsequent treatment [1]. Potent, unregulated drugs are made available over the counter, further increasing the likelihood of generating more resistant bacterial species [7]. Antibiotics 2021, 10, 435 over the counter, further increasing the likelihood of generating more resistant bacterial species [7]. Acidic, and alkaline shocks are generally more effective on Gram-positive bacteria due to their cell walls’ constituents. Biofilms formed by Gram-positive bacteria that possess a thicker cell wall show greater resistance to CAP [25]. Gram-negative bacteria experience destabilization of the outer membrane, thereby increasing the permeability barrier that leads to the release of periplasmic proteins [27]. Higher temperatures damage the cell wall, causing a depletion of magnesium, leading to disruption of ribosomes’ stability [29]. This thermotolerance is achieved by the de novo protein synthesis, which is abolished after cooling [30]

UV Light
Pressure
Electric Field
Nanotechnology
Nanozymes—Nanoparticles Mimicking Enzymes
Polymer Nanoparticles
Antibacterial Surfaces
Adaptation and Resistance of Bacteria to Nanomaterials
Bacteriophages
Phages Against Bacterial Infections
Innate Mechanisms
Chemical Defense
Abortive Defense
Bacterial Resistance Mechanisms
Discussion and Future
Full Text
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