ReviewPathogen proteomes during infection: A basis for infection research and novel control strategies
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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.
References (67)
- et al.
Lack of development of new antimicrobial drugs: a potential serious threat to public health
Lancet Infect Dis
(2005) - et al.
Extended-spectrum beta-lactamase-producing Enterobacteriaceae: an emerging public-health concern
Lancet Infect Dis
(2008) Proteomic analysis of Salmonella enterica serovar typhimurium isolated from RAW 264.7 macrophages: identification of a novel protein that contributes to the replication of serovar typhimurium inside macrophages
J Biol Chem
(2006)- et al.
Proteome analysis of separated male and female gametocytes reveals novel sex-specific Plasmodium biology
Cell
(2005) Transgenic, fluorescent Leishmania mexicana allow direct analysis of the proteome of intracellular amastigotes
Mol Cell Proteomics
(2008)- et al.
Interpretation of shotgun proteomic data: the protein inference problem
Mol Cell Proteomics
(2005) - et al.
In vivo proteomic analysis of the intracellular bacterial pathogen, Francisella tularensis, isolated from mouse spleen
Biochem Biophys Res Commun
(2006) - et al.
Optimization of GFP levels for analyzing Salmonella gene expression during an infection
FEBS Lett
(2002) - et al.
Phosphoproteome analysis of E. coli reveals evolutionary conservation of bacterial Ser/Thr/Tyr phosphorylation
Mol Cell Proteomics
(2008) - et al.
Typhoid and paratyphoid fever
Lancet
(2005)
Antimicrobial resistance in nontyphoidal Salmonella
J Food Prot
System-level analysis of Salmonella metabolism during infection
Curr Opin Microbiol
The use of genomics in microbial vaccine development
Drug Discov Today
Immune responses dependent on antigen location in recombinant attenuated Salmonella typhimurium vaccines following oral immunization
FEMS Immunol Med Microbiol
Resistance or decreased susceptibility to glycopeptides, daptomycin, and linezolid in methicillin-resistant Staphylococcus aureus
Curr Opin Pharmacol
Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America
Clin Infect Dis
Proteomic analysis of differentially expressed Chlamydia pneumoniae genes during persistent infection of HEp-2 cells
Infect Immun
Proteins unique to intraphagosomally grown Mycobacterium tuberculosis
Proteomics
Quantitative proteomics of intracellular Porphyromonas gingivalis
Proteomics
Analysis of the Plasmodium falciparum proteome by high-accuracy mass spectrometry
Nature
A proteomic view of the Plasmodium falciparum life cycle
Nature
A comprehensive survey of the Plasmodium life cycle by genomic, transcriptomic, and proteomic analyses
Science
Proteomic profiling of Plasmodium sporozoite maturation identifies new proteins essential for parasite development and infectivity
PLoS Pathog
Gel free analysis of the proteome of intracellular Leishmania mexicana
Mol Biochem Parasitol
Evaluation of two-dimensional gel electrophoresis-based proteome analysis technology
Proc Natl Acad Sci USA
Dynamics of bacterial growth and distribution within the liver during Salmonella infection
Cell Microbiol
Analysis of the Pasteurella multocida outer membrane sub-proteome and its response to the in vivo environment of the natural host
Proteomics
Robust Salmonella metabolism limits possibilities for new antimicrobials
Nature
A combined transcriptome and proteome survey of malaria parasite liver stages
Proc Natl Acad Sci USA
Examination of Salmonella gene expression in an infected mammalian host using the green fluorescent protein and two-colour flow cytometry
Mol Microbiol
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