Francisella tularensis Subtype A.II Genomic Plasticity in Comparison with Subtype A.I.
Although Francisella tularensis is considered a monomorphic intracellular pathogen, molecular genotyping and virulence studies have demonstrated important differences within the tularensis subspecies (type A). To evaluate genetic variation within type A strains, sequencing and assembly of a new subtype A.II genome was achieved for comparison to other completed F. tularensis type A genomes. In contrast with the F. tularensis A.I strains (SCHU S4, FSC198, NE061598, and TI0902), substantial genomic variation was observed between the newly sequenced F. tularensis A.II strain (WY-00W4114) and the only other publically available A.II strain (WY96-3418). Genome differences between WY-00W4114 and WY96-3418 included three major chromosomal translocations, 1580 indels, and 286 nucleotide substitutions of which 159 were observed in predicted open reading frames and 127 were located in intergenic regions. The majority of WY-00W4114 nucleotide deletions occurred in intergenic regions, whereas most of the insertions and substitutions occurred in predicted genes. Of the nucleotide substitutions, 48 (30%) were synonymous and 111 (70%) were nonsynonymous. WY-00W4114 and WY96-3418 nucleotide polymorphisms were predominantly G/C to A/T allelic mutations, with WY-00W4114 having more A+T enrichment. In addition, the A.II genomes contained a considerably higher number of intact genes and longer repetitive sequences, including transposon remnants than the A.I genomes. Together these findings support the premise that F. tularensis A.II may have a fitness advantage compared to the A.I subtype due to the higher abundance of functional genes and repeated chromosomal sequences. A better understanding of the selective forces driving F. tularensis genetic diversity and plasticity is needed.
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
Marilynn A
MA
Larson
Department of Electrical Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
Ufuk
U
Nalbantoglu
Department of Electrical Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
Khalid
K
Sayood
OpGen Inc., Gaithersburg, Maryland, United States of America.
Emily B
EB
Zentz
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
Amanda M
AM
Bartling
Naval Medical Research Center, Fort Detrick, Maryland, United States of America.
Stephen C
SC
Francesconi
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
Paul D
PD
Fey
United States Air Force School of Aerospace Medicine, Wright-Patterson Air Force Base, Ohio, United States of America.
Michael P
MP
Dempsey
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
Steven H
SH
Hinrichs
D004269:DNA, Bacterial / Q000032:analysis; D005604:Francisella tularensis / Q000145:classification* / Q000235:genetics*; D056084:Genetic Fitness; D014644:Genetic Variation; D016680:Genome, Bacterial; D054643:INDEL Mutation; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA / Q000379:methods*; D014178:Translocation, Genetic
D004269:DNA, Bacterial