Applied mass spectrometry-based proteomics in infectious diseases

Abstract

Infectious diseases caused by bacterial pathogens are common, and their impact can be measured in economic losses, but more importantly, in the loss of lives and the deterioration of quality of life, as they remain among the leading causes of death worldwide. To develop strategies that reduce their impact, understanding the molecular mechanisms of the pathogens is essential. Therefore, this research presents specific examples of how mass spectrometry-based proteomics is applied to study the molecular mechanisms of infectious diseases from the pathogen perspective.

State-of-the-art mass spectrometers, which provide high-throughput, high sensitivity, and specificity, were used to identify species-specific proteins and peptides on the surfaces of two of the deadliest bacteria: Staphylococcus aureus and Streptococcus pneumoniae (Papers I and II). Combined with surface shaving, this targeted approach enabled the identification of virulence factors and surface proteins found in multiple strains of these species, indicating promising candidates in diagnostics.

Antimicrobial resistance is undoubtedly one of the primary concerns in modern medicine. In Paper III, a resistant strain of Escherichia coli exhibits a complex interplay of factors that contribute to the development of the resistant phenotype. ABC transporters, two-component system proteins, and metabolic pathways, such as vitamin and cofactor metabolism, are affected, all of which are identified and quantified through a proteomics-based labeled quantification approach.

The study's findings offer insights into the molecular components that can serve as biomarkers or targets for treating bacterial infections and identify processes that could be targeted to combat antimicrobial resistance.