viewpointviewpoint Future trends and challenges in pathogenomics A Foresight study Sven Pompe, Judith Simon, Peter M. Wiedemann & Christof Tannert he difficult thing about the future is remains an important task at the beginning review, we used both academic search that it is so hard to predict. After the of the twenty-first century. It is in this engines and direct access to scientific TSecond World War, the availability of context that we conducted our Foresight journals. The search was conducted using vaccines and antibiotics and the successes study, ‘Future Trends and Challenges in the following keywords and combinations of improved hygiene and public health Pathogenomics’, as part of the EU-funded of terms: pathogenomics, infectious policies led to such a dramatic fall in ERA-NET project PathoGenoMics, to pro- disease, public health, bacteria, fungi, mortality that in 1969 the US Surgeon vide an overview of current and future bioweapons, bioterrorism, human pathogen. General claimed that “we can close the trends and challenges in the field of From the 3,542 resulting hits, we selected book on infectious diseases.” In hindsight, genomic research on pathogenic micro- 186 review articles, abstracts and press his prediction of the future was utterly organisms. Clearly, a Foresight study is not releases, and analysed them for further wrong—infectious diseases are back with a crystal ball to peek into the future, but trends and challenges in research, threats a vengeance. Nearly 25% of the annual it does allow the identification of impor- to public health and current bottlenecks deaths worldwide are directly related to tant trends in science, as well as perceived in commercial drug and vaccine dev- pathogens (Morens et al, 2004); multidrug- gaps in research, and places them in elopment. resistant tuberculosis and HIV/AIDS are the context of future challenges for on the rise worldwide; and Staphylococcus public health. ne clear trend is that, according and Enterococcus strains in Western hospi- to Weinstock (2000), the study of tals are becoming increasingly resistant to …infectious diseases can no Opathogenic microorganisms is antibiotics. In addition, the rapid spread undergoing major changes, triggered of new pathogens, such as the SARS longer be seen as problems of by the availability of whole genome (severe acute respiratory syndrome) and developing countries, now that sequences, new screening technologies, West Nile viruses, has shown the frailty global trade and tourism enable proteomics, comparative genomics and of global public health, which is further the rapid distribution of bioinformatics. These technologies, in affected by tourism and trade. Experts in infectious organisms combination with conventional methods security and public health also worry of serology and the cultivation of strains, that publicly available scientific informa- are becoming increasingly important for tion and advanced genetic technologies We pursued a dual approach, conducting the classification and evolutionary analy- could be misused to create weapons both a survey with national and interna- sis of microorganisms (Lederberg, 2000). for bioterrorism. tional experts in the field of patho- Molecular fingerprinting, single-nucleotide To overcome these threats to human genomics and an extensive literature polymorphism analyses and molecular health, research on pathogenic microbes research. For the survey, we developed epidemiology allow the study of the mole- and the development of new diagnostics, questionnaires and emailed them to 329 cular processes during infection, includ- vaccines and therapeutic strategies experts in research on human-pathogenic ing inflammation and host immune microorganisms and related fields. We responses, and the function of cell-surface …trends and developments in received 65 replies and 40 completed proteins and bacterial secretion systems. questionnaires; an overall reply rate of In vivo expression analyses and new basic research have to be put into 19.8 % and a return rate of 12.2 %, which bioimaging techniques to measure gene context with current and future are satisfactory (Comley, 1997; Totten, expression and protein transport now challenges for public health 2002; Sheehan, 2001). For the literature enable scientists to investigate the role of 600 EMBO reports VOL 6 | NO 7 | 2005 ©2005 EUROPEAN MOLECULAR BIOLOGY ORGANIZATION viewpoint science & society individual genes during infection in real sidebar titled ‘Important challenges for time (Doyle et al, 2004). All these techno- basic research’). IMPORTANT CHALLENGES FOR logical advances and their application in In general, these new technologies are BASIC RESEARCH microbiology contribute to a better under- needed to understand more clearly the standing of host–microbe interactions and nature of infection, so as to devise new Methods immune responses on the molecular and strategies against infectious organisms. An •Automated high-throughput methods physiological level. important goal will be the identification of (microarray technology) •Genomics, transcriptomics, metabolomics specific target genes for DNA chips used and proteomics in clinical diagnostics and for the develop- There are also many aspects in •Improvement of serology, spectroscopy, the medical system itself that ment of new antibiotics and vaccines. chromatography and microscopy According to Weinstock (2000), the dis- pose a threat to public health •In vivo approaches (animal models, covery of such target genes will not be a bioimaging, real-time PCR) major problem, rather the development of •Novel technologies (for example, microfluids, According to Hatfull & Jacobs (2000) high-throughput methods to test the effi- siRNA, multiplex assays) there has also been much progress in cacy of new therapeutics. Furthermore, he •Whole-genome sequencing and studying the genetics of infection and forecasts that candidate genes will be bioinformatics pathogenesis, as well as the communica- identified and will be in commercial use Understanding ways of infection tion between microorganisms. But much long before scientists are able to under- •Comparative and functional genomics more needs to be known; Parsek & Fuqua stand fully the molecular mechanisms of •Factors of virulence and resistance (mobile (2004) highlight the importance of infection and pathogenesis. pathogenic elements) research on surface-associated pathogens, •Host switching and antigen diversity (genome such as biofilms or planktonic cultures, nother important research area, plasticity) which has so far been neglected. Such particularly in light of new and •Immune response (defensins, inflammation) knowledge will help researchers to under- Are-emerging diseases, concerns the •Role of surface proteins stand the complex interactions between dynamics of microbe populations and microbes, whereas modelling of stress the effects of environmental factors on Understanding pathogenesis factors in the environment can elucidate these populations. These include the nat- •Communication between species (biofilm, intestinal linings) interactions between microbes and host ural reservoirs of pathogens and their •Effects of DNA methylation and identification factors. In this context, the identification geographical distributions, differentiation of conserved DNA regions of virulence factors and secreted effectors between generalists and specialists among •Factors and mechanisms of pathogenicity that modulate the human immune system, human-pathogenic agents, and microbe– (secretion systems) such as exotoxins, small molecules or environment interactions (Cleaveland et al, •Host–microbe interaction extracellular enzymes, is another impor- 2001). According to Woolhouse and col- •In-host competition tant goal. To meet the increasing problem leagues (2001), population biology will •SNP analysis and molecular epidemiology of antibiotic resistance, basic research explain the evolutionary dynamics of path- should also concentrate on the detection ogenic specialization and the stress Diagnostics and analysis of mobile pathogenic ele- responses of microbes. Woolhouse (2002) •Chronic infections and chronic inflammation ments and resistance transfer through also emphasizes the importance of study- •Development of specific antibodies genomic islands (Hacker & Carniel, ing routes of pathogen transmission •Identification and classification of human- 2001). Another important development is through vectors (such as arthropods) and pathogenic bacteria and fungi the fusion of cell biology with microbiology, direct (for example, physical contact) or •Identification of toxins, small molecules and which will be of great importance for indirect contact (such as through food). allergenic compounds studying the in situ expression of genes Ultimately, this epidemiological research •Specific DNA arrays to identify species in (Roux et al, 2004). Denning and col- will contribute to the early identification of polymicrobial cultures leagues (2003) note recent advances in novel and re-emerging diseases caused by microscopy, such as multidimensional bacteria, fungi and multi-resistant bacterial Clinical importance imaging, laser-scanning microscopy, epi- strains. In this context, the understanding •Development of new diagnostic and therapeutic agents fluorescence microscopy and fluorescent of immune selection and the impact of •Evaluation of effects of chemotherapeutics light-based imaging, while stressing the vaccination and antibiotic intervention (such as antibiotics) importance of microscopy