Sunday, January 3, 2010

E. coli-like genes in the spirochete Brachyspira hyodysenteriae, the agent of swine dysentery

The genus Brachyspira comprises at least seven species of anaerobic spirochetes that live in the large intestines of various birds and animals (including humans).  One species, Brachyspira hyodysenteriae, causes swine dysentery, a disease that causes economic loss among pig farmers worldwide.  Afflicted pigs produce loose stools covered with mucus and blood.  In severe cases, necrotic chunks of colon lining are expelled with the stool.

An Australian group sequenced the genome of B. hyodysenteriae strain WA1 to figure out how the spirochete thrives in the complex nutritional environment of the large intestine and induces swine dysentery.  They found 2,122 protein-coding genes distributed between a 3,000,694 bp chromosome and a 35,940 bp plasmid.  A number of genes encoded degradative enzymes such as proteases, phospholipases, and hemolysins that may or may not account for the damage to the colon observed in swine dysentery cases.  Otherwise, no obvious pathogenic mechanism for the disease process could be gleaned from the genome sequence.

Remarkably, half of the proteins encoded in the B. hyodysenteriae genome were most similar in sequence to proteins of Escherichia and Clostridium, genera that are not even on the same branch on the bacterial evolutionary tree as spirochetes.  A mere 6.4% of B. hyodysenteriae proteins matched best to proteins of other spirochetes.


From Table 3 of Bellgard 2009.

Among the Escherichia- and Clostridium-like genes, those encoding proteins involved with amino acid and sugar metabolism and transport were over-represented.  Since E. coli, Clostridium species, and B. hyodysenteriae all live in the large intestine, the similarity in the proteins may simply reflect convergent evolution that enable the bacteria to metabolize the nutrients available in the colon.  The more attractive possibility is that B. hyodysenteriae acquired the genes from the other enteric bacteria by horizontal gene transfer thereby allowing the spirochete to adapt to the complex nutritional environment of the large intestine.  At least for the E. coli-like genes, examining their GC content may help distinguish between the two possibilities since the GC content of B. hyodysenteriae is only 27% versus 50% for E. coli.

How can B. hyodysenteriae acquire genes from other enteric bacteria?  A commentary in the journal Gut Pathogens raised the possibility that bacteriophage-like elements found in the B. hyodysenteriae genome could be involved, although bacteriophages generally do not transfer DNA between different species of bacteria.  Another possibility is that genes could be acquired from other bacteria by conjugation, a form of microbial mating.  Although the capacity of B. hyodysenteriae for acquiring DNA from other bacteria by conjugation is unknown, scientists have demonstrated that another spirochete could acquire DNA from E. coli by conjugation in the laboratory setting.

Image source

Sow with piglet, from Wikipedia

References

Bellgard, M.I., Wanchanthuek, P., La, T., Ryan, K., Moolhuijzen, P., Albertyn, Z., Shaban, B., Motro, Y., Dunn, D.S., Schibeci, D., Hunter, A., Barrero, R., Phillips, N.D., and Hampson, D.J. (2009).  Genome sequence of the pathogenic intestinal spirochete Brachyspira hyodysenteriae reveals adaptations to its lifestyle in the porcine large intestine.  PLoS ONE 4(3):e4641. DOI: 10.1371/journal.pone.0004641

Hampson, D.J. and Ahmed, N. (2009).  Spirochaetes as intestinal pathogens:  Lessons from a Brachyspira genome.  Gut Pathogens 1(1):10.  DOI: 10.1186/1757-4749-1-10

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