Bacterial Defense and Evolutionary Escape from Non-Conventional Antimicrobials

The rise of antimicrobial-resistant pathogens presents a serious threat to human and animal health, potentially leading to millions of deaths in the coming years. As traditional antimicrobials become less effective, attention is increasingly focused on developing alternative antimicrobials and therapeutic strategies. These methods aim to combat antibiotic-resistant bacteria and slow the development of resistance. Promising options include antimicrobial peptides, nanobiotics, Trojan Horse antimicrobials, quorum-sensing quenchers, anti-virulence agents, antimicrobial photodynamic therapy, and biological antibacterials such as predatory bacteria, probiotics, and bacteriophages. Antimicrobial peptides and nanobiotics attack bacteria via multiple mechanisms, while photodynamic therapy employs reactive oxygen species to target various bacterial components. This diversity of mechanisms makes it more difficult for bacteria to develop resistance than when faced with conventional antibiotics. Quorum-sensing quenchers and anti-virulence agents disarm bacterial virulence factors without killing the bacteria, thereby reducing selective pressure for resistance. Predatory bacteria operate through distinct mechanisms involving multiple effectors, making them effective against antibiotic-resistant strains and limiting the emergence of resistance.

Although non-conventional therapies employ complex mechanisms that challenge bacterial defenses, bacteria remain highly adaptable and have evolved strategies to counter these treatments. These defenses include sequestration, degradation or modification of antimicrobials, target modification, remodeling of the bacterial envelope, activation of detoxification systems, production of secondary metabolites, and population-level responses such as biofilm formation.

Developing effective non-conventional therapies requires a thorough understanding of these bacterial strategies. This Research Topic seeks articles that examine the defensive mechanisms used by pathogens to evade non-conventional antimicrobials, including but not limited to the following areas:
- Genetic and evolutionary basis of bacterial defensive responses against non-conventional antimicrobials
- Novel bacterial defense mechanisms against non-conventional therapies
- Structural and molecular characterization of effectors involved in bacterial defense responses to non-conventional therapies
- Impact of resistance to non-conventional therapies on pathogen virulence
- Emerging population-level responses, such as biofilm formation, relevant to non-conventional therapies

Article types welcomed include original research, reviews, perspectives, and methods articles.



Topic Editor Sushma Kommineni is employed by and holds shares in BioNTech US Inc. The other Topic Editors report no competing interests related to this Research Topic.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Non-conventional antimicrobials, Bacterial defense mechanisms, evolutionary adaptation, alternative antibacterial therapies, anti-virulence strategies, biofilm formation, bacteriophages

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.