Bacillus subtilis as a Model for Bacterial Systems Biology

Abstract

Bacillus subtilis has been the subject of intense study for nearly six decades. Initially, the key drivers were: (i) the need of the food industry for a nonpathogenic model bacterium to study the characteristics of endospores, and (ii) the observation, in 1959, that B. subtilis strain 168 could be genetically manipulated by transformation. In the intervening period, B. subtilis 168 has become second only to Escherichia coli K‐12 in terms of the detail with which aspects of its genetic, biochemistry and physiology is understood. For the foreseeable future, B. subtilis represents an eminently tractable model in which to integrate knowledge gained from the reductionist approach to biology towards an understanding of how this bacterium functions as a unitary system. This will require the application of various ‘omics’ (e.g. genomics, transcriptomics, proteomics, metabolomics), the increased application of high‐throughput technologies and system modelling. The ultimate aim of an in silico model of B. subtilis is that it can accurately mimic or predict its behaviour in the environment.

Keywords: systems biology; proteomic; transcriptomics; metabolomics; cell factory

Figure 1.

The use of integration vectors as genome management tools. Non‐replicating integration vectors can be used to: (a) inactivate specific chromosomal genes via a single crossover recombination between regions of homology on the vector and chromosome; (b) deliver target genes to non‐essential regions of the chromosome (here the amyE gene encoding α‐amylase) via a double crossover recombination of the linearized vector. Abbreviations: AbrBsu, antibiotic resistance gene active in B. subtilis; AbrEco, antibiotic resistance gene active in E. coli; amyE5’/amyE3’, fragments of the B. subtilis amyE gene; Ori‐Eco, origin of replication active in E. coli.

Figure 2.

Complementation analysis in B. subtilis of the PrsA homologues of B. subtilis and B. anthracis using compatible chromosomal integrational expression vectors. Abbreviations: amyE5/amyE3′, fragments of the B. subtilis amyE gene; bla, ampicillin resistance gene active in E. coli; cat, chloramphenicol resistance gene active in B. subtilis; erm, erythromycin resistance gene active in B. subtilis; lacI, encoding the lactose repressor of E. coli; lacZ, encoding β‐galactosidase of E. coli; Ori‐Eco, origin of replication active in E. coli; prsA, B. subtilis gene encoding PrsA; prsAA, B. anthracis gene encoding PrsAA; PprsA, native promoter of the B. subtilis prsA gene; Pxyl, xylose‐inducible promoter; RBS+5′prsA, fragment carrying the ribosome binding site and 5′ sequences of the B. subtilis prsA gene.

Figure 3.

The generation of ‘clean’ chromosome deletions using the pVWO1‐based vector pORI240. Abbreviations: lacZ, encoding β‐galactosidase from E. coli; Tcr, tetracycline resistance gene.

Figure 4.

Showing the main commercial products synthesized in B. subtilis and its close relatives. Bacillus species are major producers of industrial enzymes (e.g. α‐amylases, serine proteases), vitamins and food supplements (e.g. riboflavin, biotin, nucleosides), peptide antibiotics (e.g. gramicidin, polymyxin, tyrocidine) and heterologous proteins.

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Further Reading

Sonenshein AL, Hoch JA and Losick R (eds) (2002) Bacillus subtilis and it closest relatives: From genes to cells. Washington DC: ASM Press.

Schumann W, Ehrlich SD and Ogasawara N (eds) (2001) Functional analsysis of bacterial genes: A practical approach. Chichester: Wiley.

Thompson DK and Zhou J (2004) The functional genomics of model organisms: addressing old questions from a new perspective. In: Zhou J, Thompson DK, Xu Y and Tiedje JM (eds) Microbial Functional Genomics. New Jersey: Wiley.

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Harwood, Colin R(Apr 2007) Bacillus subtilis as a Model for Bacterial Systems Biology. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0002027]