title: Functional genomic characterization of virulence factors from necrotizing fasciitis-causing strains of Aeromonas hydrophila.
abstract: The genomes of 10 Aeromonas isolates identified and designated Aeromonas hydrophila WI, Riv3, and NF1 to NF4; A. dhakensis SSU; A. jandaei Riv2; and A. caviae NM22 and NM33 were sequenced and annotated. Isolates NF1 to NF4 were from a patient with necrotizing fasciitis (NF). Two environmental isolates (Riv2 and -3) were from the river water from which the NF patient acquired the infection. While isolates NF2 to NF4 were clonal, NF1 was genetically distinct. Outside the conserved core genomes of these 10 isolates, several unique genomic features were identified. The most virulent strains possessed one of the following four virulence factors or a combination of them: cytotoxic enterotoxin, exotoxin A, and type 3 and 6 secretion system effectors AexU and Hcp. In a septicemic-mouse model, SSU, NF1, and Riv2 were the most virulent, while NF2 was moderately virulent. These data correlated with high motility and biofilm formation by the former three isolates. Conversely, in a mouse model of intramuscular infection, NF2 was much more virulent than NF1. Isolates NF2, SSU, and Riv2 disseminated in high numbers from the muscular tissue to the visceral organs of mice, while NF1 reached the liver and spleen in relatively lower numbers on the basis of colony counting and tracking of bioluminescent strains in real time by in vivo imaging. Histopathologically, degeneration of myofibers with significant infiltration of polymorphonuclear cells due to the highly virulent strains was noted. Functional genomic analysis provided data that allowed us to correlate the highly infectious nature of Aeromonas pathotypes belonging to several different species with virulence signatures and their potential ability to cause NF.
authors.affiliation: Food and Drug Administration, Laurel, Maryland, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Grim
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Kozlova
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Duraisamy
authors.initials: D
authors.lastname: Ponnusamy
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Fitts
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Sha
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Kirtley
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Christina J
authors.initials: CJ
authors.lastname: van Lier
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Bethany L
authors.initials: BL
authors.lastname: Tiner
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Tatiana E
authors.initials: TE
authors.lastname: Erova
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Sandeep J
authors.initials: SJ
authors.lastname: Joseph
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Read
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Shak
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, USA Maryland Institute of Applied Environmental Health, School of Public Health, University of Maryland, College Park, Maryland, USA.
authors.forename: Sam W
authors.initials: SW
authors.lastname: Joseph
authors.affiliation: Doctors Hospital, Augusta, Georgia, USA.
authors.forename: Ed
authors.initials: E
authors.lastname: Singletary
authors.affiliation: Mercy Hospital and Trauma Center, Janesville, Wisconsin, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Felland
authors.affiliation: Department of Veterinary Sciences, M. D. Anderson Cancer Center, Bastrop, Texas, USA.
authors.forename: Wallace B
authors.initials: WB
authors.lastname: Baze
authors.affiliation: Pathology and Laboratory Medical Services, VA Maryland Health Care System, Baltimore, Maryland, USA.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Horneman
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA achopra@utmb.edu.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Chopra
mesh_terms: D016980:Aeromonas hydrophila / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D000818:Animals; D018441:Biofilms / Q000254:growth & development; D004269:DNA, Bacterial / Q000235:genetics; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000378:metabolism; D019115:Fasciitis, Necrotizing / Q000382:microbiology*; D005260:Female; D005618:Fresh Water / Q000382:microbiology; D005798:Genes, Bacterial; D056726:Genetic Association Studies; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology; D006801:Humans; D051379:Mice; D010802:Phylogeny; D010930:Plague / Q000382:microbiology; D010957:Plasmids / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D037521:Virulence Factors / Q000235:genetics*; D014871:Water Microbiology
chemical_list: D004269:DNA, Bacterial; D004768:Enterotoxins; D037521:Virulence Factors