17 Current Opinion in Microbiology 2002, 5:17–19 1369-5274/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved Host–microbe interactions: bacteria Microbes and their hosts: mutual interactions Editorial overview Matthew K Waldor and Arturo Zychlinsky Matthew K Waldor Tufts University School of Medicine and Howard Hughes Medical Institute, Division of Geographic Medicine and Infectious Diseases, NEMC #041, 750 Washington Street, Boston, Massachusetts 02111, USA; e-mail: mwaldor@lifespan.org Matt studies the biology of mobile genetic elements that encode viru- lence factors, and the ways in which these elements influence production of the virulence factors they encode. Arturo Zychlinsky Max Planck Institute for Infection Biology, Campus Charité Mitte, Schumannstrasse 21/22, 14163 Berlin, Germany; e-mail: zychlinsky@MPIIB-Berlin.MPG.DE Using Shigella and Salmonella as model organisms, Arturo’s research focuses on apoptosis as a bacterial pathogenic mechanism. Introduction Bacterial infection results in disease when host tissues are damaged. How does tissue damage occur? The view that bacteria cause non-specific damage because they grow in the ‘culture broth’ of host organs is proving to be incorrect. Instead, studies of both bacterial pathogens and their hosts are revealing the specificity with which virulence factors interact with host targets and the increasing discovery of host molecules that recognize and signal the presence of bacteria. The sophisticated ways in which bacterial proteins manipulate host signal transduction cascades are also becoming apparent. We are beginning to understand both how bacteria manipulate host defences, particularly the innate immune system, to survive, and how bacteria can induce the host to self-inflict the damage. Genomes and genetics These are very exciting and fast-moving times in pathogenesis research. The complete genomes of most bacterial pathogens are now known, and powerful genetic and bioinformatic tools have been developed to explore the molecular bases of microbial pathogenicity. The technology to discover virulence genes and their specific functions has received a strong impetus with the advent of genomics. Two reviews in this Host–microbe interactions: bacteria issue, by Schoolnik (pp 20–26) and by Sassetti and Rubin (pp 27–32), discuss how we can mine these enormous genomic databases to understand pathogenesis. They propose that the comparative use of genomic information as well as the use of genome information in microarrays be used as a method to generate a ‘dictionary’ of a bacterium’s pathogenic lexicon. The lexicon can be decoded by intra- and interspecies comparison, as well as by cataloguing when genes are expressed across a gamut of conditions. Array studies from the bacterial pathogen and the host cell can eventually be combined using sophisticated bioinformatics. Ultimately, however, the functional importance of pathogen and host genes identified in microarray studies must be validated by other means. In a more ‘classic’ genetic approach, signature-tagged mutagenesis is designed to select in vivo for genes required for bacterial pathogenesis. Mecsas (pp 33–37) reviews recent data from several laboratories at which this approach has yielded interesting results. Research has led not only to the discovery of genes necessary to cause disease, but also to identification of attenuated strains that have the potential to become vaccine candidates. In addition, signature tags have been used to reveal how bacteria spread through host tissues. How do prokaryotes communicate with eukaryotes? Studies of the complex interactions between bacteria and their hosts have recently advanced on several fronts. Orth (pp 38–43) describes a striking new example of co-evolution between a bacterium and its host. YopJ is a Yersinia effector protein that is delivered to the host cell cytoplasm by a type III secretion apparatus. It is a cysteine protease that cleaves proteins that have been