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BMC Microbiol. 2012; 12: 167.
Published online Aug 6, 2012. doi:  10.1186/1471-2180-12-167
PMCID: PMC3462115
Phenotypic and Genomic Analysis of Hypervirulent Human-associated Bordetella bronchiseptica
Umesh Ahuja,1 Minghsun Liu,1 Shuta Tomida,2 Jihye Park,4 Puneet Souda,3 Julian Whitelegge,3 Huiying Li,2 Eric T Harvill,4 Julian Parkhill,5 and Jeff F Millercorresponding author1
1Department of Microbiology, Immunology and Molecular Genetics, University of California, BSRB 254, 615 Charles E. Young Drive East, Los Angeles, CA, 90095-1747, USA
2Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, University of California, Los Angeles, USA
3The Pasarow Mass Spectrometry Laboratory, The NPI-Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, USA
4Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, Pennsylvania, USA
5Pathogen Sequencing Unit, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
corresponding authorCorresponding author.
Umesh Ahuja: uahuja/at/ucla.edu; Minghsun Liu: lmh/at/ucla.edu; Shuta Tomida: shuta/at/ucla.edu; Jihye Park: jup139/at/psu.edu; Puneet Souda: psouda/at/chem.ucla.edu; Julian Whitelegge: jpw/at/chem.ucla.edu; Huiying Li: huiying/at/mednet.ucla.edu; Eric T Harvill: eth10/at/psu.edu; Julian Parkhill: parkhill/at/sanger.ac.uk; Jeff F Miller: jfmiller/at/ucla.edu
Received May 1, 2012; Accepted July 17, 2012.
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.
Keywords: B. bronchiseptica, Hypervirulence, Cytotoxicity, Bordetella evolution, Host adaptation, Pathogenomics
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