Virulence Diversity among Bacteremic Aeromonas Isolates: Ex Vivo, Animal, and Clinical Evidences

Abstract

BackgroundThe objective of this study was to compare virulence among different Aeromonas species causing bloodstream infections.Methodology/Principal FindingsNine of four species of Aeromonas blood isolates, including A. dhakensis, A. hydrophila, A. veronii and A. caviae were randomly selected for analysis. The species was identified by the DNA sequence matching of rpoD. Clinically, the patients with A. dhakensis bacteremia had a higher sepsis-related mortality rate than those with other species (37.5% vs. 0%, P = 0.028). Virulence of different Aeromonas species were tested in C. elegans, mouse fibroblast C2C12 cell line and BALB/c mice models. C. elegans fed with A. dhakensis and A. caviae had the lowest and highest survival rates compared with other species, respectively (all P values <0.0001). A. dhakensis isolates also exhibited more cytotoxicity in C2C12 cell line (all P values <0.0001). Fourteen-day survival rate of mice intramuscularly inoculated with A. dhakensis was lower than that of other species (all P values <0.0001). Hemolytic activity and several virulence factor genes were rarely detected in the A. caviae isolates.Conclusions/SignificanceClinical data, ex vivo experiments, and animal studies suggest there is virulence variation among clinically important Aeromonas species.

A Disease Model of Muscle Necrosis Caused by Aeromonas dhakensis Infection in Caenorhabditis elegans

“…Therefore, C. elegans can be a feasible model to study the pathogenesis of muscle necrosis. Our previous studies illustrated the applicability of virulence findings about Aeromonas species in C. elegans to mammalian cells, mice, and humans (Chen et al, 2014a,b). Clinical Aeromonas isolates that were virulent in C. elegans were also lethal to mice.…”

“…In some endemic areas, such as southern Taiwan, A. dhakensis is of clinical importance due to its virulence and antimicrobial resistance, and it is also the predominant species in wound infections (Chen et al, 2014a,b). In addition, the whole-genome sequence of the A. dhakensis strain AAK1 has been published (Wu et al, 2012), and genomic information of C. elegans is readily available, making further and systematic genetic studies of host-microbe interaction possible.…”

“…To obtain a synchronously growing population, eggs were prepared by treating a population of C. elegans with hypochlorite/NaOH solution and transferring the resulting eggs to NGM plates covered with E. coli OP50, as previously described (Chen et al, 2014b). The synchronized adult L4 worms on NGM plates were washed in M9 buffer.…”

“…Here, we specifically studied the pathogenesis of A. dhakensis in an animal host. The reasons for choosing A. dhakensis were: (1) A. dhakensis can cause severe soft-tissue infections in animal models and humans (Chen et al, 2014a,b); (2) A. dhakensis carries a number of virulence genes responsible for developing infectious diseases and its virulence has been recognized as the most potent among clinically important Aeromonas species (Figueras et al, 2009; Morinaga et al, 2013; Chen et al, 2014b); (3) Increasing evidence shows that A. dhakensis is widely distributed in the environment and causes a variety of infections in humans (Figueras et al, 2009; Aravena-Roman et al, 2011; Morinaga et al, 2013; Chen et al, 2014a). These findings suggest the clinical significance of this specific type of bacterial infection.…”

“…Clinical Aeromonas isolates that were virulent in C. elegans were also lethal to mice. The histological findings of mice with Aeromonas muscular infection, such as fragmented muscle fibers, edema of myocytes, and infiltration of inflammatory cells, resembled necrotizing myositis in humans (Chen et al, 2014b). However, the detailed histopathological characterization of muscle tissues in C. elegans with Aeromonas infection remains understudied.…”