Elsevier

Journal of Proteomics

Volume 73, Issue 11, 10 October 2010, Pages 2267-2276
Journal of Proteomics

Review
Pathogen proteomes during infection: A basis for infection research and novel control strategies

https://doi.org/10.1016/j.jprot.2010.08.004Get rights and content

Abstract

Infectious diseases cause tremendous mortality and morbidity worldwide. Rising antimicrobial resistance and the lack of new drugs cause an increasingly alarming crisis in infectious disease control. New system-level approaches are likely to help understand complex host/pathogen interactions as a basis for rational development of novel antibiotics and vaccines. Proteome analysis of pathogens in infected tissues comprehensively reveals functionally relevant pathogen activities during infection. It also highlights potential targets for antimicrobial chemotherapy as well as promising antigens for vaccination. Integration of these data with complementary large-scale data helps to further prioritize candidates for in-depth experimental analysis. Here, I discuss some of these approaches with a special emphasis on the model pathogen Salmonella.

Section snippets

Infectious diseases require new system-level approaches

Infectious diseases represent a major worldwide threat to human health [1]. This situation is likely to become even worse because of a steep increase in antimicrobial resistance in many bacterial pathogens [2], [3], [4]. To control resistant pathogens, novel antibiotics are urgently needed, but unfortunately, there is a steep decline in antibiotic approvals during the last three decades (Fig. 1) [5]. This decline is somewhat surprising since fundamental research has made substantial progress in

Proteome analysis of pathogens from cell culture infection models

Diverse pathogens have been extensively analyzed using various proteomics approaches under various in vitro conditions in axenic culture (i.e., in the absence of any host cells). The relevance of these in vitro data for combating infectious diseases is unclear as most pathogens are capable of adaptation to different conditions using wide-scale remodeling of transcription, translation, and post-translational modification. In vitro pathogen proteomes are thus likely to differ markedly from those

Proteome analysis of pathogens from infected tissues

During infectious diseases, pathogens are confronted with dynamic inflammatory host responses involving multiple cell types that employ a large variety of antimicrobial effector mechanisms. These complex processes are difficult to reproduce in in vitro cell cultures. Moreover, most cell culture infection models utilize immortal cancer cell lines that are known to differ in many crucial aspects from primary cells with which pathogens are confronted in real infectious diseases. The somewhat

Functional analysis of pathogen proteins with detectable in vivo expression

The currently available long lists of identified pathogen proteins from infected tissues contain valuable information on pathogen biology during infection. However, identification of the most relevant proteins among many hundreds of detected proteins is still a considerable challenge. One way to analyze these proteome data could be to combine them with independently obtained evidence from complementary experimental techniques. Such an integrated approach requires diverse large-scale functional

Application of proteome data for infection control strategies

Proteome data offer unique insights into Salmonella activities during infection. This information can be exploited as a basis for development of novel antimicrobial chemotherapies and vaccines. In particular, identification of a pathogen protein in an in vivo proteome indicates that this protein is present during disease and thus meets at least one key precondition for qualifying as a target for effective infection control strategies. On the other hand, it is clear that even among the in vivo

Conclusion

Proteome analysis of pathogens in infected tissues provides unique information about pathogen activities during infection. Importantly, functionally relevant proteins are preferentially identified and in vivo proteome data can thus help to efficiently guide further functional analysis. Current technical limitations largely concern quantification, identification of post-translational modifications, and poor coverage of secreted proteins. Conceptual challenges include system-level analysis and

Acknowledgements

I thank past and present members of my lab for stimulating discussions and Deutsche Forschungsgemeinschaft und Schweizerischer Nationalfonds for funding.

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