Science in Society Archive

Superbug with Anthrax Genes

The Bacillus species causing anthrax and food poisoning are closely related to each other and to a third, Bacillus thuringiensis, whose toxin genes are extensively exploited to create genetically modified Bt-crops. I-SIS has warned of the potential for dangerous recombinants to emerge; such a recombinant has now been identified. Dr. Mae-Wan Ho and Prof. Joe Cummins caution against growing Bt crops, especially in the Third World.

The three Bacillus bacteria all live in the soil and are so closely related that they may as well be regarded as a single species [1]. B. anthracis, causes anthrax, B. cereus is linked to food poisoning, and B. thuriengiensis is extensively exploited as biopesticides in genetically engineered Bt crops, now widely cultivated in the United States, and increasingly being promoted in Third World countries. The three bacteria readily mate with one another and exchange plasmids (circular pieces of DNA) carrying specific toxin and virulence genes. They share very similar viruses (phages) that can integrate into the bacterial genome as ‘prophage’ [2], and can hence also move toxin and virulence genes among them, many of them reside in the bacterial chromosome. Cummins [3] has warned that dangerous recombinants could arise, from gene exchange between the bacteria and between the Bt plant debris and bacteria in the soil.

Now, an international team of infectious disease researchers led by Claire M. Fraser of the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, USA, have identified a recombinant between B. anthracis and B. cereus [4]. They were alerted last year when two hospital patients in Texas died of severe pneumonia that appeared to be caused by inhalation anthrax, but neither patient was infected with B. anthracis. Instead, DNA tests showed that both patients were infected by a strain of B. cereus that normally causes mild food poisoning, which has somehow acquired the lethal anthrax genes [5].

When the Texas cases came to light, the CDC scientists were sequencing a strain of B. cereus isolated from a man in Louisiana who, in 1994, showed up with severe anthrax-like symptoms. The Texas and Lousiana patients were all metal workers who seemed to have inhaled the bacteria.

Anthrax is an acute fatal disease among mammals and B. anthracis became widely known as a biological weapon soon after September 11, 2001. It has two plasmids: pXO1 carrying the lethal toxin complex (edema factor, lethal factor and protective antigen), and pXO2 carrying the glutamic acid polymer that inhibits white blood cells from engulfing and digesting the bacterium. Until a few years ago, B. anthracis was thought to be distinct from B. cereus, because they look different and causes different diseases.

The researchers sequenced the B. cereus genome using draft genome sequences obtained and assembled by the company Celera, and the resulting sequence annotated through The Institute for Genomic Research (TIGR) Bioinformatics pipeline, set up by Craig Venter, the maverick scientist who founded Celera to sequence the human genome, succeeded only too well, and was sacked from the company in January 2002, after he remarked on there being too few genes to support the simplistic idea that organisms are hardwired in their genes.

It turns out that the culprit strain of B. cereus G9241 had acquired a plasmid very similar to the pXO1 of B. anthracis. In addition, analysis of seven other metabolic genes showed that the strain is closely related to, albeit distinct from B. anthracis.

The sequence of B. cereus G9241 genome reveals a mosaic structure, which could be due to the presence of a great number of what appears to be known and novel mobile genetic elements that can insert sequences from other sources. It also has a 119 110bp circular plasmid with high similarity to B. anthracis pXO1. There is, further, a cryptic phage of 29 886bp that encodes phage-like proteins and a plasmid replicon (replicating unit) similar to B. anthracis plasmid pXO2. It also carries genes that, if functional, should provide the strain with resistance to b-lactam, chloramphenicol and macrolide antimicrobial agents.

When injected into mice, B. cereus G9241 proved to be 100% lethal, as was B. anthracis, but it killed the mice almost twice as fast. All the mice injected with an ordinary B. cereus strain survived the experiment.

As a result of these findings, the researchers concluded that, "it may not be appropriate to consider B. anthracis, as currently defined, as the only species capable of causing inhalation anthrax-like disease."

Another noteworthy feature is that at least two isolates of B. cereus (ATCC 14579) and M 1550) are extremely closely related to and cluster with B. thuringiensis. A number of delta endotoxins from B. thuringiensis strains are implicated in allergies and other illnesses, or known to be immunogenic [6-8]. What sort of disease agent might emerge from B. cereus if it acquired endotoxin genes either from B. thuringiensis or from Bt crop debris in the soil? This question is especially pertinent in view of the substantial changes in the genetically modified Bt genes that are completely untested and hence unknown in toxicities.

Countries, especially those in the Third World, where farmers live next to their fields, should be particularly wary about growing Bt crops.

Article first published 16/06/04



References

  1. Helgason E, AndreasOkstadt O, Caugant D, Johannsen H, Fouet A, Mock M, Hegna I, and Kolsto A. Bacillus anthracis, Bacillus cereus and Bacillus thuringiensis: One species on the basis of genetic evidence. Applied and Enviromental Microbiology 2000, 66, 2627-30.
  2. Strömsten NJ, Benson SD, Burnett RM, Bamford DH and Bamford JKH. The Bacillus thuringiensis linear double-stranded DNA phage Bam35, which is highly similar to the Bacillus cereus linear plasmid pBClin15. J Bacteriol 2003, 185, 6985-9.
  3. Cummins J. Biopesticide and bioweapons. ISIS Report, 23 October 2001
  4. Hoffmaster AR, Ravel J, Rasko DA et al. Identification of anthrax toxin genes in a Bacillus cereus associated with an illness resembling inhalation anthrax. PNAS 2004, 101, 8449-54.
  5. "Deaths blamed on mysterious microbe with anthrax genes", Kate Ruder, Genome News Network 4 June, 2004.
  6. Cummins J. Regulatory sham over Bt-crops. ISIS report 1 December 2003; also Science in Society 2004, 21, 30.
  7. Cummins J. Bt toxins in genetically modified crops: regulation by deceit. Science in Society 2004, 22.
  8. Ho MW and Cummins J. GM food and feed not fit for "man or beast". ISIS Report, 7 May 2004

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