Navigating ESKAPE Pathogens: Considerations and Caveats for Animal Infection Models Development

Area of Science:

• Microbiology and Infectious Diseases
• Translational Medicine
• Animal Models of Disease

Background:

• Antibiotic misuse drives the global rise of multi-drug-resistant (MDR) bacteria, particularly ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species).
• These opportunistic pathogens are a major cause of nosocomial infections, leading to significant patient morbidity and mortality, especially in hospital settings.
• Understanding ESKAPE pathogenesis, virulence, host immune responses, and developing effective diagnostics and therapeutics necessitate reliable experimental systems.

Purpose of the Study:

• To critically evaluate the role and limitations of animal infection models in studying ESKAPE pathogens.
• To identify key considerations for developing and utilizing effective animal models for research on these critical pathogens.
• To bridge knowledge gaps in understanding ESKAPE pathogenesis and guide targeted therapeutic development.

Main Methods:

• Review and analysis of the application of various animal infection models for ESKAPE pathogens.
• Discussion of challenges, including rapid host immune clearance in immunocompetent models.
• Identification of crucial parameters for model design, including disease replication, monitoring, and data collection.

Main Results:

• No single animal model can fully recapitulate all facets of infectious diseases caused by ESKAPE pathogens.
• Host immune responses in immunocompetent models can sometimes limit the observation of characteristic disease symptoms.
• Careful selection and meticulous replication of human disease parameters are essential for reliable and informative animal models.

Conclusions:

• Animal infection models are indispensable tools for advancing the study of ESKAPE pathogens.
• Addressing model limitations through thoughtful design and execution maximizes their potential for research.
• Improved animal models will accelerate the development of novel therapeutics and strategies to combat MDR ESKAPE pathogens and protect public health.