There is a very interesting new paper that just came online in the Archives of Pathology: Rapidly Progressive, Fatal, Inhalation Anthrax-Like Infection in a Human: Case Report, Pathogen Genome Sequencing, Pathology, and Coordinated Response
I was alerted to the paper by Eileen Choffnes of the National Academy of Sciences Institute of Medicine Forum on Microbial Threats (which I am a member of). In the paper, James Musser, Angela Wright and colleagues, the authors discuss the use of genome sequencing in the characterization of a fatal infection with a bacterium that appeared to be a species of Bacillus. Their summary is below and pretty much sums it up:
Context.—Ten years ago a bioterrorism event involving Bacillus anthracis spores captured the nation’s interest, stimulated extensive new research on this pathogen, and heightened concern about illegitimate release of infectious agents. Sporadic reports have described rare, fulminant, and sometimes fatal cases of pneumonia in humans and nonhuman primates caused by strains of Bacillus cereus, a species closely related to Bacillus anthracis.
Objectives.—To describe and investigate a case of rapidly progressive, fatal, anthrax-like pneumonia and the overwhelming infection caused by a Bacillus species of uncertain provenance in a patient residing in rural Texas.
Design.—We characterized the genome of the causative strain within days of its recovery from antemortem cul- tures using next-generation sequencing and performed immunohistochemistry on tissues obtained at autopsy with antibodies directed against virulence proteins of B. anthracis and B. cereus.
Results.—We discovered that the infection was caused by a previously unknown strain of B. cereus that was closely related to, but genetically distinct from, B. anthracis. The strain contains a plasmid similar to pXO1, a genetic element encoding anthrax toxin and other known virulence factors. Immunohistochemistry demonstrated that several homologs of B. anthracis virulence proteins were made in infected tissues, likely contributing to the patient’s death.
Conclusions.—Rapid genome sequence analysis permit- ted us to genetically define this strain, rule out the like- lihood of bioterrorism, and contribute effectively to the institutional response to this event. Our experience strongly reinforced the critical value of deploying a well- integrated, anatomic, clinical, and genomic strategy to respond rapidly to a potential emerging, infectious threat to public health.
The part in which I am interested, not surprisingly, is the genomic-evolution part. This is of interest since Bacillus anthracis is in a way a subspecies of a larger clade of bacterial types that includes Bacillus cereus and Bacillus thuringensis. These two generally do not cause fatal disease in humans, though I believe there are prior cases (see for example, Anthrax, but not Bacillus anthracis?). Also, I note, B. thuringensis is also known as Bt and is used extensively in agriculture to kill pests. Anyway, though Bt abd Bc are known to occasionally cause humans trouble, without a doubt, if you say you have found a case of Bacillus anthracis in people, some serious freaking out will occur at some level. People will want to know things – like is this a natural occurrence or a purposeful attack? And in the end, there is a lot associated with the name since of course “anthrax” scares people.
One of us recently proposed the inception of a third, training track in pathology termed genomic pathology, designed to complement the traditional anatomic and clinical pathology tracks. As the introgression of genome- scale analyses proceeds rapidly and inexorably into con- temporary patient care and pathology practice, the career opportunities for this new type of trainee will increase considerably, and new patient-care niches will be created. We believe cases such as this highlight the need for, and potential utility of, a cadre of pathologists trained and facile in genomic pathology.
- Accurate, rapid and high-throughput detection of strain-specific polymorphisms in Bacillus anthracis and Yersinia pestis by next-generation sequencing.
- Historical distribution and molecular diversity of Bacillus anthracis, Kazakhstan.
- The genome and variation of Bacillus anthracis.
- Anthrax, but not Bacillus anthracis?
- Global genetic population structure of Bacillus anthracis.
- The Genome of a Bacillus Isolate Causing Anthrax in Chimpanzees Combines Chromosomal Properties of B. cereus with B. anthracis Virulence Plasmids
Reference:
Wright AM, Beres SB, Consamus EN, Long SW, Flores AR, Barrios R, Richter GS, Oh SY, Garufi G, Maier H, Drews AL, Stockbauer KE, Cernoch P, Schneewind O, Olsen RJ, & Musser JM (2011). Rapidly Progressive, Fatal, Inhalation Anthraxlike Infection in a Human: Case Report, Pathogen Genome Sequencing, Pathology, and Coordinated Response. Archives of pathology & laboratory medicine PMID: 21827220
Are you certain we don't need genomic pathomics?
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never sure about anything … but that certainly seems bad
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The tree is based on MLST, ie. 7 loci. The full sequence analysis shows that reads mapped to plasmid pXO1. The fact that B. cererus has a plasmid is not novel, ie:
http://www.ncbi.nlm.nih.gov/pubmed/15155910
My question is, where is the sequence data?
Why do editors allow sequence and genome analysis to be published with the data being submitted to the archives?
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Of for f*cks sake – really? The data is not out there. Uggh — let's see what we can do about this — stay tuned
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I think the highlight of this paper and the other papers that Jonathan cites here (full disclosure – I am the an author of one of the E. coli ones) is the fact that the sequencing is entering a time frame to become an important piece of the diagnostic process. It no longer takes weeks, months, years to generate genome data, we are into days and some of the newer technologies less than a day. These times put genomics squarely into the realm of being a diagnostic tool. Looking forward to the next years.
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