Whole genomic sequence analysis of Bacillus infantis: defining the genetic blueprint of strain NRRL B-14911, an emerging cardiopathogenic microbe

Authors: MASSILAMANY, C - University Of Nebraska; MOHAMMED, AKRAM - Nebraska Medical Center; LOY, JOHN - University Of Nebraska; PURVIS, TANYA - Kansas State University; KRISHNAN, BHARATHI - University Of Nebraska; BASAVALINGAPPA, RAKESH - University Of Nebraska; Kelley, Christy; GUDA, CHITTIBABU - Nebraska Medical Center; BARLETTA, RAUL - University Of Nebraska; MORIYAMA, ETSUKO - University Of Nebraska; Smith, Timothy - Tim; REDDY, JAY - University Of Nebraska

Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/12/2016
Publication Date: 8/22/2016
Citation: Massilamany, C., Mohammed, A., Loy, J.D., Purvis, T., Krishnan, B., Basavalingappa, R.H., Kelley, C.M., Guda, C., Barletta, R.G., Moriyama, E.N., Smith, T.P.L., Reddy, J. 2016. Whole genomic sequence analysis of Bacillus infantis: defining the genetic blueprint of strain NRRL B-14911, an emerging cardiopathogenic microbe. Biomed Central (BMC) Genomics. 17(Suppl. 7):511. doi: 10.1186/s12864-016-2900-2.

Interpretive Summary: Recently, there has been an emerging hypothesis that some common diseases may be caused by immune responses to proteins produced from bacteria that are not normally thought of as pathogenic. One particular protein was identified in the database of bacterial proteins, that had resemblance to a known immune-response-stimulating peptide that has been implicated in development of some cases of cardiac disease in humans. However, the genome sequence of the organism predicted to produce the protein was not very well known or annotated, as the genome assembly had been performed before the development of new technologies that enable high-quality finished genomes without the years-long efforts that used to be required. Using this new technology available at ARS in Clay Center, Nebraska, a high-quality, complete circular genome of the bacteria was produced. The genome and the organism, originally isolated from seawater, were subjected to a number of analyses that will facilitate testing of the hypothesis of the relationship of bacterial protein exposure to cardiac disease.

Technical Abstract: Background: We recently reported the identification of Bacillus sp. NRRL B-14911 that induces heart autoimmunity by generating cardiac-reactive T cells through molecular mimicry. This marine bacterium was originally isolated from the Gulf of Mexico, but no associations with human diseases were reported. Therefore, to characterize its biological and medical significance, we sought to determine and analyze the complete genome sequence of Bacillus sp. NRRL B-14911. Results: Based on the phylogenetic analysis of 16S ribosomal RNA (rRNA) genes, sequence analysis of the 16S-23S rDNA intergenic transcribed spacers, phenotypic microarray, and matrix-assisted laser desorption ionization time-offlight mass spectrometry, we propose that this organism belongs to the species Bacillus infantis, previously shown to be associated with sepsis in a newborn child. Analysis of the complete genome of Bacillus sp. NRRL B-14911 revealed several virulence factors including adhesins, invasins, colonization factors, siderophores and transporters. Likewise, the bacterial genome encodes a wide range of methyl transferases, transporters, enzymatic and biochemical pathways, and insertion sequence elements that are distinct from other closely related bacilli. Conclusions: The complete genome sequence of Bacillus sp. NRRL B-14911 provided in this study may facilitate genetic manipulations to assess gene functions associated with bacterial survival and virulence. Additionally, this bacterium may serve as a useful tool to establish a disease model that permits systematic analysis of autoimmune events in various susceptible rodent strains.