Quantitative proteomics analysis of pertussis: Uncovering biomarkers for diagnosis and disease monitoring and insights into pathogenesis

• Comprehensive Proteomic Analysis of Pertussis: Utilized quantitative proteomics analysis to study pertussis bacteremia, pneumonia, and non-complicated cases. Identified and quantified 49,985 peptides corresponding to 4659 proteins. • Biomarker Identification: Discovered distinct protein profiles across different infection types. ADH6 and TTC38 were upregulated in pertussis sepsis, LRRC42 was downregulated in pertussis pneumonia. These proteins may serve as potential biomarkers for diagnosis and disease monitoring. • Insights into Disease Progression: During pertussis sepsis progression, NCOA3 increased and KCRS decreased from disease onset to improvement, and SAA2 surged in the recovery stage. These protein expression changes provide insights into the mechanisms of disease progression and recovery. • Prognosis Markers: In comparing pertussis sepsis patients with different outcomes, PTMS, NNMT, and ASSY were downregulated in the deceased patient. These proteins may be used as molecular markers for prognosis. • Pathogenesis Understanding: Enrichment analysis and protein - protein interaction network analysis enhanced understanding of pertussis pathogenesis. Revealed biological processes related to bacterial survival and metabolism in pertussis sepsis and cell - cell communication and tissue structure maintenance in pertussis pneumonia. Pertussis, a highly contagious respiratory disease caused by Bordetella pertussis, remains a significant global health challenge despite vaccination efforts. China has witnessed a resurgence of cases, especially among young children. The diverse clinical manifestations and non-specific symptoms hinder early diagnosis. This study utilized quantitative proteomics analysis to explore differential protein expression in pertussis bacteremia, pneumonia, and non-complicated cases. The key findings include distinct protein profiles across different infection types, which suggest potential biomarkers and offer insights into disease severity and progression. Specifically, proteins such as ADH6 and TTC38 were significantly upregulated in pertussis sepsis, while LRRC42 was downregulated in pertussis pneumonia. During the progression of pertussis sepsis, NCOA3 increased and KCRS decreased from disease onset to improvement, and SAA2 surged in the recovery stage. In comparing pertussis sepsis patients with different outcomes, PTMS, NNMT, and ASSY were downregulated in the deceased patient.These findings enhance our understanding of pertussis pathogenesis, providing crucial insights for the development of more effective vaccines, diagnostics, and treatments, ultimately aiming to reduce the global burden of this infectious disease. This study utilized quantitative proteomics to analyze pertussis. It identified differential protein expression in various pertussis cases, revealing potential biomarkers for diagnosis and disease monitoring, and providing insights into pathogenesis.