The lactic acid bacteria (LAB) might be the most numerous group of bacteria linked to humans. They are naturally associated with mucosal surfaces, particularly the gastrointestinal tract, and are also indigenous to food-related habitats, including plant (fruits, vegetables, and cereal grains), wine, milk, and meat environments (60, 61). The LAB include both important pathogens, e.g., several Streptococcus species, and extremely valuable nonpathogenic species that are used for industrial fermentation of dairy products, meats, and vegetables, and they are also critical for the production of wine, coffee, silage, cocoa, and sourdough (13, 60, 61). In addition, the LAB are a priceless source of antimicrobial agents, the bacteriocins (reference 10 and references therein).
The term LAB mainly refers to the defining feature of the basal metabolism of these bacteria, the fermentation of hexose sugars yielding, primarily, lactic acid. Various aspects of LAB biology and application are thoroughly covered in several books by Wood and Holzapfel and Wood and Warner (60, 61) and numerous reviews, including those in a recent specialized issue of FEMS Microbiology Reviews (12, 14, 18, 20, 23, 24, 31, 39, 42, 49, 58). The definition of LAB is biological rather than taxonomical, i.e., the LAB do not comprise a monophyletic group of bacteria. Most of the LAB belong to the order Lactobacillales, a group of nonsporulating, gram-positive bacteria, but a few LAB species belong to the Actinobacteria (60).
The early sequencing of LAB genomes involved mostly bacteria of the genus Streptococcus, which encompasses most of the pathogenic LABs (50, 60). Currently, 19 complete genomes of streptococci are available, covering different strains of five species. A program aimed at extensive sequencing of the genomes of nonpathogenic LAB was announced in 2002 by the Lactic Acid Bacteria Genome Sequencing Consortium (19), but the actual breakthrough occurred only in the last 2 years (2005 and 2006). At the time of writing (August 2006), 18 complete genome sequences of the nonpathogenic LAB representing 14 species from the order Lactobacillales were available (Table (Table1)1) . The Lactobacillales have relatively small genomes for nonobligatory bacterial parasites or symbionts (characteristic genome size, ~2 megabases, with ~2,000 genes), with the number of genes in different species spanning the range from ~1,600 to ~3,000. This variation in the number of genes suggests that the evolution of LAB involved active processes of gene loss, duplication, and acquisition. The current collection of LAB genomes is a unique data set that includes multiple related genomes with a gradient of divergence in sequences and genome organizations. This set of related genomes is amenable to detailed reconstruction of genome evolution, which is not yet attainable with other groups of bacteria.
This review is largely based on recent work on comparative genomic analysis of 12 nonpathogenic LAB from the order Lactobacillales (Table (Table1)1) (28). We briefly discuss the customized comparative-genomic framework that was developed for the LAB and its application to evolutionary reconstruction and functional genomics.