Extensive antibody cross-reactivity among infectious gram-negative bacteria revealed by proteome microarray analysis

Area of Science:

• Microbiology
• Immunology
• Proteomics

Background:

• Antibodies are sensitive indicators of bacterial proteins during sepsis.
• Host immunity can amplify infection signals to detect low-level biomarkers.
• Current methods may struggle to differentiate between pathogens with similar initial symptoms.

Purpose of the Study:

• To develop antibody biomarkers for distinguishing plague from other bacterial infections.
• To identify specific and shared proteins across various pathogenic bacteria.
• To leverage host immune responses for enhanced pathogen detection.

Main Methods:

• Developed a microarray of Yersinia pestis proteome (approx. 70% of 4066 proteins).
• Examined rabbit antibodies against proteomes from Y. pestis and other Gram-negative bacteria (e.g., Burkholderia spp., Pseudomonas aeruginosa, Salmonella typhimurium, Shigella flexneri, Escherichia coli).
• Analyzed antigen binding patterns using sera from infected non-human primates.

Main Results:

• Identified shared cross-reactive proteins, fingerprint proteins (common to multiple bacteria), and signature proteins (specific to one pathogen).
• Antibody recognition of Y. pestis proteins involved less than 100 out of thousands.
• Distinguished plague from anthrax (Bacillus anthracis) using primate sera.

Conclusions:

• Demonstrated the potential of antibody biomarkers for pathogen identification.
• Developed a method to identify proteins specific to one bacterial strain or common to several species.
• Highlighted the utility of host immunity in discovering novel diagnostic markers for infectious diseases.