TY - JOUR
T1 - Phenotypic and genomic analysis of hypervirulent human-associated bordetella bronchiseptica
AU - Ahuja, Umesh
AU - Liu, Minghsun
AU - Tomida, Shuta
AU - Park, Jihye
AU - Souda, Puneet
AU - Whitelegge, Julian
AU - Li, Huiying
AU - Harvill, Eric T.
AU - Parkhill, Julian
AU - Miller, Jeff F.
N1 - Funding Information:
We thank Jane Park, Linda Phung and Ning Chang for technical assistance and Katya Panina, Christopher T. French, Atish Ganguly and Diego Arambula for helpful discussions. We thank Dave Richards for his assistance with animal experiments. This work was partly supported by NIH RO1 AI061598 to JFM and a Swiss National Science Foundation post doctoral fellowship award PBEZA-113867 to UA.
PY - 2012
Y1 - 2012
N2 - Abstract. Background: B. bronchiseptica infections are usually associated with wild or domesticated animals, but infrequently with humans. A recent phylogenetic analysis distinguished two distinct B. bronchiseptica subpopulations, designated complexes I and IV. Complex IV isolates appear to have a bias for infecting humans; however, little is known regarding their epidemiology, virulence properties, or comparative genomics. Results: Here we report a characterization of the virulence of human-associated complex IV B. bronchiseptica strains. In in vitro cytotoxicity assays, complex IV strains showed increased cytotoxicity in comparison to a panel of complex I strains. Some complex IV isolates were remarkably cytotoxic, resulting in LDH release levels in A549 cells that were 10- to 20-fold greater than complex I strains. In vivo, a subset of complex IV strains was found to be hypervirulent, with an increased ability to cause lethal pulmonary infections in mice. Hypercytotoxicity in vitro and hypervirulence in vivo were both dependent on the activity of the bsc T3SS and the BteA effector. To clarify differences between lineages, representative complex IV isolates were sequenced and their genomes were compared to complex I isolates. Although our analysis showed there were no genomic sequences that can be considered unique to complex IV strains, there were several loci that were predominantly found in complex IV isolates. Conclusion: Our observations reveal a T3SS-dependent hypervirulence phenotype in human-associated complex IV isolates, highlighting the need for further studies on the epidemiology and evolutionary dynamics of this B. bronchiseptica lineage.
AB - Abstract. Background: B. bronchiseptica infections are usually associated with wild or domesticated animals, but infrequently with humans. A recent phylogenetic analysis distinguished two distinct B. bronchiseptica subpopulations, designated complexes I and IV. Complex IV isolates appear to have a bias for infecting humans; however, little is known regarding their epidemiology, virulence properties, or comparative genomics. Results: Here we report a characterization of the virulence of human-associated complex IV B. bronchiseptica strains. In in vitro cytotoxicity assays, complex IV strains showed increased cytotoxicity in comparison to a panel of complex I strains. Some complex IV isolates were remarkably cytotoxic, resulting in LDH release levels in A549 cells that were 10- to 20-fold greater than complex I strains. In vivo, a subset of complex IV strains was found to be hypervirulent, with an increased ability to cause lethal pulmonary infections in mice. Hypercytotoxicity in vitro and hypervirulence in vivo were both dependent on the activity of the bsc T3SS and the BteA effector. To clarify differences between lineages, representative complex IV isolates were sequenced and their genomes were compared to complex I isolates. Although our analysis showed there were no genomic sequences that can be considered unique to complex IV strains, there were several loci that were predominantly found in complex IV isolates. Conclusion: Our observations reveal a T3SS-dependent hypervirulence phenotype in human-associated complex IV isolates, highlighting the need for further studies on the epidemiology and evolutionary dynamics of this B. bronchiseptica lineage.
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U2 - 10.1186/1471-2180-12-167
DO - 10.1186/1471-2180-12-167
M3 - Article
C2 - 22863321
AN - SCOPUS:84864498082
SN - 1471-2180
VL - 12
JO - BMC microbiology
JF - BMC microbiology
M1 - 167
ER -