The capacity for some pathogens to jump into different host-species populations is a major threat to public health and food security. Staphylococcus aureus is a multi-host bacterial pathogen responsible for important human and livestock diseases. Here, using a population-genomic approach, we identify humans as a major hub for ancient and recent S. aureus host-switching events linked to the emergence of endemic livestock strains, and cows as the main animal reservoir for the emergence of human epidemic clones. Such host-species transitions are associated with horizontal acquisition of genetic elements from host-specific gene pools conferring traits required for survival in the new host-niche. Importantly, genes associated with antimicrobial resistance are unevenly distributed among human and animal hosts, reflecting distinct antibiotic usage practices in medicine and agriculture. In addition to gene acquisition, genetic diversification has occurred in pathways associated with nutrient acquisition, implying metabolic remodelling after a host switch in response to distinct nutrient availability. For example, S. aureus from dairy cattle exhibit enhanced utilization of lactose-a major source of carbohydrate in bovine milk. Overall, our findings highlight the influence of human activities on the multi-host ecology of a major bacterial pathogen, underpinned by horizontal gene transfer and core genome diversification.

The heyday of continuous culture was in the 1960s, when its versatility and reproducibility were used to address fundamental problems in diverse microbiological fields such as biochemistry, ecology, genetics and physiology. The advent of molecular genetics in the 1970s and 1980s led to a decline in the popularity of continuous culture as a standard laboratory tool. The current trend of studying global proteomics, transcriptomics and metabolomics requires reproducible, reliable and biologically homogeneous datasets with which to approach a given problem. The use of continuous culture techniques can aid the acquisition of such data, and continuous cultures offer advantages over biologically heterogeneous batch cultures, where secondary growth and stress effects can often mask subtle physiological differences and trends. This review is intended to remind microbiologists of the value of continuous cultivation in a wide range of biological investigations, and describes some advantages and recent advances in applications of continuous culture in post-genomic studies.

Streptomyces coelicolor is a Gram-positive soil bacterium that undergoes a complex developmental life cycle. The genome sequence of this organism was recently completed and has revealed the presence of over 60 sigma factors and a multitude of other transcriptional regulators, with a significant number of these being putative two-component signal transduction proteins. The authors have used the criteria established by Hoch and co-workers (Fabret et al., 1999, J Bacteriol 181, 1975-1983 to identify sensor kinase and response regulator genes encoded within the S. coelicolor genome. This analysis has revealed the presence of 84 sensor kinase genes, 67 of which lie adjacent to genes encoding response regulators. This strongly suggests that these paired genes encode two-component systems. In addition there are 13 orphan response regulators encoded in the genome, several of which have already been characterized and are implicated in development and antibiotic production, and 17 unpaired and as yet uncharacterized sensor kinases. This article attempts to infer useful information from sequence analysis and reviews what is currently known about the two-component systems, unpaired sensor kinases and orphan response regulators of S. coelicolor from both published reports and the authors' own unpublished data. Two-component signal transduction systems (TCSs), consisting of a sensor kinase (SK) and a cognate response regulator (RR), are found across all three domains of life, the Bacteria, Archaea and Eukarya. They are most widespread in the Bacteria (with the exception of the mycoplasmas) but SK genes have also been identified in the Archaea (Kim & Forst, 2001), in fungi and protozoa (Thomason & Kay, 2000), and in plants (Hwang et al., 2002). SK genes are conspicuously absent from the animal genomes so far sequenced and it has been proposed that these proteins are not present in the animal kingdom as a whole (Wolanin et al., 2002). This potentially makes them an attractive target for antimicrobials (Barrett et al., 1998), especially since some bacteria, including Bacillus subtilis and the opportunistic pathogen Staphylococcus aureus, contain essential TCSs (Fabret & Hoch, 1998;Martin et al., 1999). The extracytoplasmic sensor domain of each SK responds to specific types of environmental stimuli. The signal is transferred via autophosphorylation of a conserved His residue in the cytoplasmic H box to the aspartate residue of the cognate RR, which then activates transcription of target genes (Hakenbeck & Stock, 1996; Fig. 1). In bacteria, generally speaking the range of environmental stimuli to which an organism can respond is directly linked to the number of SKs encoded by that organism's genome. The number of SKs encoded by a bacterial genome is also proportional to the size of the genome, such that in bacteria which are obligate pathogens, and generally have smaller genomes, the percentage of SK and RR pairs in relation to the total number of genes is quite small, approximately 0?26 % compared to 0?65 % in free-living bacter...

We review known evolutionary mechanisms underlying the overwhelming chemical diversity of bacterial natural products biosynthesis, focusing on enzyme promiscuity and the evolution of enzymatic domains that enable metabolic traits.

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Prokaryotic systematics provides the fundamental framework for microbiological research but remains a discipline that relies on a labour- and time-intensive polyphasic taxonomic approach, including DNA-DNA hybridization, variation in 16S rRNA gene sequence and phenotypic characteristics. These techniques suffer from poor resolution in distinguishing between closely related species and often result in misclassification and misidentification of strains. Moreover, guidelines are unclear for the delineation of bacterial genera. Here, we have applied an innovative phylogenetic and taxogenomic approach to a heterogeneous actinobacterial taxon, Rhodococcus, to identify boundaries for intrageneric and supraspecific classification. Seven species-groups were identified within the genus Rhodococcus that are as distantly related to one another as they are to representatives of other mycolic acid containing actinobacteria and can thus be equated with the rank of genus. It was also evident that strains assigned to rhodococcal species-groups are underspeciated with many misclassified using conventional taxonomic criteria. The phylogenetic and taxogenomic methods used in this study provide data of theoretical value for the circumscription of generic and species boundaries and are also of practical significance as they provide a robust basis for the classification and identification of rhodococci of agricultural, industrial and medical/veterinary significance.

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The human immune system has evolved in the context of our colonisation by bacteria, viruses, fungi and parasitic helminths. Reflecting this, the rapid eradication of pathogens appears to have resulted in reduced microbiome diversity and generation of chronically activated immune systems, presaging the recent rise of allergic, autoimmune and metabolic disorders. Certainly, gastrointestinal helminths can protect against gut and lung mucosa inflammatory conditions by modulating the microbiome and suppressing the chronic inflammation associated with dysbiosis. Here, we employ ES-62, an immunomodulator secreted by tissue-dwelling Acanthocheilonema viteae to show that helminth-modulation of the gut microbiome does not require live infection with gastrointestinal-based worms nor is protection restricted to mucosal diseases. Specifically, subcutaneous administration of this defined immunomodulator affords protection against joint disease in collagen-induced arthritis, a mouse model of rheumatoid arthritis, which is associated with normalisation of gut microbiota and prevention of loss of intestinal barrier integrity.