Author
SUKUMAR, NEELIMA - Cornell University | |
Nicholson, Tracy | |
CONOVER, MATT - Wake Forest University | |
DEORA, RAJENDAR - Wake Forest University |
Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 1/24/2014 Publication Date: 4/1/2014 Citation: Sukumar, N., Nicholson, T.L., Conover, M.S., Ganguly, T., Deora, R. 2014. Comparative analyses of a cystic fibrosis isolate of Bordetella bronchiseptica reveal differences in important pathogenic phenotypes. Infection and Immunity. 82(4):1627-1637. Interpretive Summary: Bacteria belonging to the group known as Bordetella typically cause respiratory infections. Bordetella pertussis, for example, causes whooping cough in humans, while Bordetella bronchiseptica causes respiratory infections in animals such as cats, rabbits and pigs. Although not usually thought of as a human pathogen, Bordetella bronchiseptica infections in humans are reported. It is important to know if there is anything unique about the strains of bacteria that transmit and cause disease in humans. We studied a strain of Bordetella bronchiseptica isolated from a cystic fibrosis patient that was believed to be transmitted from the family cat. Differences were found between the strain isolated from the cystic fibrosis patient and a typical Bordetella bronchiseptica strain that causes disease in animals. For example, the strain from the cystic fibrosis patient was better able to attach to human respiratory cells. This type of information will help us understand and predict when certain strains of Bordetella bronchiseptica have the potential to transmit and cause disease in humans and help us restrict these events. Technical Abstract: While not considered a human pathogen, B. bronchiseptica infections in humans are reported and demonstrate zoonotic transmission into humans. An extensive characterization of these strains is needed to better understand the genetic and phenotypic traits associated with these zoonotic transmission events. Here we report the molecular and phenotypic characterization of a B. bronchiseptica strain, T44625, obtained from a cystic fibrosis patient. This strain is phylogenetic sequence type (ST) 27 strain, which is found in Clonal Complex 1 of an MLST-based Bordetella phylogeny. Unlike most other STs in Complex 1, the overwhelming majority of ST27 isolates have been isolated from human infections. Using whole genome transcriptome and comparative genomic hybridization (CGH) analysis we demonstrate that strain T44625 contains a distinct genomic content of virulence associated genes and differentailly expresses these virulence related genes compared to sequenced laboratory reference strain RB50. The differential expression pattern of virulence related genes correlated with the unique phenotypes exhibited by strain T44625, which included an increased in vitro adherence capacity of strain T44625 to adhere to respiratory epithelial cells of both human and animal origin and a hyper-biofilm phenotype. Using a mouse infection model, we also demonstrate that although defective in establishing high bacterial burdens early during the infection process, strain T44625 is capable of establishing a persistent infection in the mouse nasal cavity. The unique genomic and phenotypic qualities of strain T44625 provide a blueprint for understanding the successful zoonotic potential of this strain. |