Chemotactic invasion in deep soft tissue by Vibrio vulnificus is essential for the progression of necrotic lesions

Abstract

Necrotizing soft tissue infections (NSTI) progress to severe necrosis and result in fatal sepsis within a short time. Vibrio vulnificus is a causative agent and can spread from the initial infection site through soft tissue finally to the systemic circulation of the host. The motility and chemotaxis of this bacterium are essential for proliferation and lethality in a murine model of the infection, but their role in pathogenicity has not been characterized. In this study, we revealed the roles of motility and chemotaxis during the process of V. vulnificus infection. We compared a nonmotile mutant and two nonchemotactic mutants with their parent strain (WT) with regard to bacterial spread using an in vivo imaging system (IVIS) and invasion by detection of bacteria from the muscle and spleen of a murine infection model. WT rapidly spread throughout the infected thigh and invaded deep muscle causing severe tissue damage. The detection rate in the systemic circulation and the lethality were high. On the other hand, the nonmotile mutant stayed at the inoculation site, and the nonchemotactic mutants spread only slowly through the soft tissue of the infected thigh. Detection in the systemic circulation, the degree of tissue damage, and the lethality of nonchemotactic mutants were significantly reduced in mice compared with WT. This study demonstrated that chemotaxis is essential for invasion from the infection site to the deep and distant tissues and the main pathogenic factor for the rapid progression leading to sepsis in V. vulnificus NSTI.

Expansion of Necrosis Depending on Hybrid Motor-Driven Motility of Aeromonas hydrophila in a Murine Wound Infection Model

“…Vibrio vulnificus is also one of the causative agents of NSTI, and clinical syndromes resulting from infection with A. hydrophila resemble those due to Vibrio vulnificus. A motility-deficient mutant of V. vulnificus had reduced proliferation ability and pathogenicity at the site of infection [31]. However, the proliferation ability of A. hydrophila was not affected by lack of motility as shown in this study.…”

“…The effects of motility on bacterial pathogenicity have been reported in a study on Vibrio vulnificus wound infection [ 31 , 42 , 43 ]. Vibrio vulnificus is also one of the causative agents of NSTI, and clinical syndromes resulting from infection with A. hydrophila resemble those due to Vibrio vulnificus .…”

“…The motA / motB (hereafter motAB ) and pomA / pomB (hereafter pomAB ) deletion mutants were constructed by the same method for the mutant construction of Vibrio vulnificus [ 31 ]. Briefly, the motAB gene and the pomAB gene were amplified and cloned into the suicide vector pYAK1, retaining sacB .…”

Host-Pathogen Adhesion as the Basis of Innovative Diagnostics for Emerging Pathogens

“…The severity of an infectious disease depends on the level of invasiveness and the extent of host cell and tissue damage caused by the pathogen involved [ 8 ]. A varying degree of virulence can be observed across different pathogens and among different strains of a single pathogen [ 9 ].…”

MukB Is a Gene Necessary for Rapid Proliferation of Vibrio vulnificus in the Systemic Circulation but Not at the Local Infection Site in the Mouse Wound Infection Model

“…These factors could be targeted to develop effective treatments for septicemia. In a murine infection model, several factors have already been reported: a capsular polysaccharide, lipopolysaccharide, repeats-in- toxins, an iron acquisition system, and chemotactic ability [ 6 , 7 , 8 , 9 ]. However, the mechanisms causing severe and rapid septicemia resulting from V. vulnificus infection have not been fully understood.…”