Functional Genomic Characterization of Virulence Factors from Necrotizing Fasciitis-Causing Strains of Aeromonas hydrophila

• Type of Material: Article
• Authors: Christopher J. Grim, Food and Drug Administration; Elena V. Kozlova, University of Texas Medical Branch; Duraisamy Ponnusamy, University of Texas Medical Branch; Eric C. Fitts, University of Texas Medical Branch; Jian Sha, University of Texas Medical Branch; Michelle L. Kirtley, University of Texas Medical Branch; Christina J. van Lier, University of Texas Medical Branch; Bethany L. Tiner, University of Texas Medical Branch; Tatiana E. Erova, University of Texas Medical Branch; Sandeep J. Joseph, Emory University; Timothy Read, Emory University; Joshua R. Shak, Emory University; Sam W. Joseph, University of Maryland; Ed Singletary, Doctors Hospital; Tracy Felland, Mercy Hospital and Trauma Center; Wallace B. Baze, MD Anderson Cancer Center; Amy J. Horneman, VA Maryland Health Care System; Ashok K. Chopra, University of Texas Medical Branch
• Language: English
• Date: 2014-07-01
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2014, American Society for Microbiology.
• Final Published Version (URL): http://dx.doi.org/10.1128/AEM.00486-14
• Title of Journal or Parent Work: Applied and Environmental Microbiology
• ISSN: 0099-2240
• Volume: 80
• Issue: 14
• Start Page: 4162
• End Page: 4183
• Grant/Funding Information: The financial support provided to A.K.C. through Leon Bromberg and Robert E. Shope and John S. Dunn Distinguished Chair in Global Health endowments, UTMB, is gratefully acknowledged.
• Keywords: CLINICAL ISOLATE; Microbiology; PSEUDOMONAS-AERUGINOSA; Life Sciences & Biomedicine; BIOTECHNOLOGY & APPLIED MICROBIOLOGY; Biotechnology & Applied Microbiology; IN-VIVO VIRULENCE; MICROBIOLOGY; SOFT-TISSUE INFECTIONS; AERUGINOSA EXOTOXIN-A; SECRETION SYSTEM EFFECTOR; N-ACYLHOMOSERINE LACTONES; INTESTINAL EPITHELIAL-CELLS; CYTOTOXIC ENTEROTOXIN; BIOFILM FORMATION; Science & Technology
• Research Categories: Biology, Microbiology; Biology, Cell

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.