78 The sequencing of the Bacillus anthracis genome and virulence plasmids represents the greatest advance in anthrax research in the past 100 years. The data will provide the foundation of all future work on this organism and will be invaluable to researchers in their battle to understand the basis of the host–microbe interaction. Addresses *Pathobiology, Biomedical Sciences, DERA Porton Down, Salisbury SP4 0JQ, UK; e-mail: lesbaillie@hotmail.com † The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850, USA; e-mail: tread@tigr.org Current Opinion in Microbiology 2001, 4:78–81 1369-5274/01/$ —see front matter © 2001 Elsevier Science Ltd. All rights reserved. Abbreviations EF oedema factor LF lethal factor PA protective antigen Introduction In this review, we will describe Bacillus anthracis, its viru- lence factors and what is known about the basis of the host–pathogen interaction. The work that is in progress to determine the genetic sequence of the organism will also be described and the exploitation of this data discussed. Anthrax is a disease caused by the bacterium B. anthracis. Although primarily a disease of animals, it can also infect man, sometimes with fatal consequences. The disease has been evident since biblical times: the fifth and sixth plagues of Egypt (Exodus, chapter 9) are considered to have been anthrax. More recently, the organism was instrumental in the founding of two modern sciences: bacteriology (Koch, 1877) and immunology (Pasteur, 1881) [1]. Since then, little atten- tion has been focused on understanding the biology of the organism, save for the fact that it possesses properties that make it ideally suited as a biological weapon. It forms heat- resistant spores that are easy to produce using commercially available technology and can infect via the aerosol route. It has been reported that at the time of the Gulf War, Iraq produced large quantities of anthrax spores and had deployed SCUD/Al-Hussein missiles equipped with biological weapons warheads [2,3 • ]. The organism B. anthracis is the only obligate pathogen within the genus Bacillus, which comprises the Gram-positive aerobic or fac- ultatively anaerobic spore-forming, rod-shaped bacteria. It is frequently convenient to class B. anthracis informally within the ‘B. cereus group’, which, on the basis of pheno- type, comprises B. cereus, B. anthracis, B. thuringiensis and B. mycoides [4 • ]. It is not possible to discriminate between species in this group based on 16S rRNA sequences. However, amplified fragment length polymorphism (AFLP) and multiple-locus VNTR (variable number tan- dem repeat) analysis (MLVA analysis) have provided clear evidence that B. anthracis can be distinguished reliably from other members of the bacilli [5,6 •• ]. In practical terms, the demonstration of virulence constitutes the principle point of difference between typical strains of B. anthracis and those of other anthrax-like organisms [4 • ,7]. Disease in man Man generally acquires the disease directly, from contact with infected livestock (known as non-industrial anthrax) or indirectly in industrial occupations concerned with processing animal products (known as industrial anthrax) [4 • ]. Three forms of the disease are recognised in humans: cuta- neous, pulmonary (inhalation) and gastrointestinal infection. The gastrointestinal and pulmonary forms are regarded as being most frequently fatal, owing to the fact that they can go unrecognised until it is too late to instigate effective treatment with the agents currently available [8 •• ]. There is an obvious need to develop therapies that can be used to treat these individuals. Cutaneous anthrax This form accounts for the majority of human cases (>95%) [8 •• ] and is usually caused by the handling of infected ani- mals or their products. The organism gains access through a break in the skin, and forms a primary lesion within two to seven days. A ring of vesicles develops around the cen- tral papule, which ulcerates and rapidly dries to form a characteristic black lesion. Most such carbuncular cases recover without treatment, but in 20% of cases, the infec- tion will progress into a generalised septicaemia with poor prognosis [8 •• ,9]. Pulmonary (inhalation) anthrax Although commonly used, the term ‘pulmonary anthrax’ is a misnomer. The lung is not the primary site of infection and a better description is ‘inhalation anthrax’. Following inhalation, spores are phagocytosed by alveolar macrophages and transported to hilar and tracheobronchial lymph nodes, where the spores germinate and multiplica- tion of vegetative bacilli occurs [10 • ]. Fatal bacteraemia and toxaemia then ensue, with a mortality rate of >80% [8 •• ,9]. Gastrointestinal anthrax Gastrointestinal anthrax is extremely rare and occurs mainly in Africa, the Middle East and central and south- ern Asia. It is rarely seen in man where the disease is infrequent or rare in livestock. Most cases of intestinal anthrax result from eating insufficiently cooked meat from anthrax-infected animals [11]. Bacillus anthracis, a bug with attitude! Les Baillie* and Timothy D Read †