Host-encoded antivirulence defenses: host physiologies teach pathogens to play nice

Area of Science:

• Infectious Disease Research
• Microbiology
• Immunology

Background:

• Current infectious disease treatments primarily rely on pathogen eradication, which drives antimicrobial resistance.
• Antivirulence strategies aim to disarm pathogens without killing them, offering a complementary approach.
• Targeting virulence factors alone may be insufficient due to pathogen adaptation and resistance evolution.

Purpose of the Study:

• To review host-evolved cooperative defenses that promote antivirulence.
• To explore mechanisms suppressing pathogen virulence without negatively impacting pathogen fitness.
• To propose a more holistic definition of antivirulence.

Main Methods:

• Literature review of antivirulence strategies and host-pathogen interactions.
• Analysis of existing definitions and proposed holistic frameworks for antivirulence.
• Exploration of co-operative host defense mechanisms.

Main Results:

• Host-evolved cooperative defenses offer a promising avenue for antivirulence.
• These mechanisms suppress pathogen virulence without compromising pathogen fitness, thus mitigating resistance.
• A unified, holistic definition of antivirulence is proposed.

Conclusions:

• Antivirulence strategies are crucial for combating infectious diseases and overcoming drug resistance.
• Host-evolved cooperative defenses represent an underexplored resource for developing novel therapeutic interventions.
• Understanding these natural defense mechanisms can lead to treatments that avoid selecting for pathogen resistance.