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

Abstract

Vibrio vulnificus causes rapid septicemia in susceptible individuals who have ingested contaminated foods or have open wounds exposed to seawater contaminated with the bacteria. Despite antibiotic therapy and aggressive debridement, mortality from septicemia is high. In this study, we showed that MukB mutation (mukB::Tn) affected the proliferation of V. vulnificus in the systemic circulation but not at the inoculation site in the wound infection model. A comparison of mukB::Tn with WT and a mukB complement strain (mukB::Tn/pmukB) on the bacterial burden in the muscle at the infection site showed that spreading and proliferation of the mukB::Tn strain was similar to those of the other strains. However, the bacterial burden of mukB::Tn in the spleen was reduced compared to that of the WT strain in the wound infection model. In a competition experiment, we found a lower bacterial burden of mukB::Tn in the spleen than that of the WT strain infecting the systemic circulation. Here, we report on a gene required for the rapid proliferation of V. vulnificus only in the systemic circulation and potentially required for its survival. Our finding may provide a novel therapeutic target for V. vulnificus septicemia.

Acyl carrier protein promotes MukBEF action in Escherichia coli chromosome organization-segregation

“…Furthermore, ΔmukB cells are inviable during rapid growth that supports overlapping replication cycles, apparently because of failures in chromosome segregation 4,6,18,20 . Because the lack of functional MukB can result in reduced proliferation in organisms that cause disease phenotypes, such as Vibrio vulnificus 21 , MukB is a potential target for new antimicrobial therapeutics 22 .…”

Increased Vascular Permeability Due to Spread and Invasion of Vibrio vulnificus in the Wound Infection Exacerbates Potentially Fatal Necrotizing Disease

“…The MARTX, required for proliferation at the site of infection, enabled the killing of phagocytic cells, thus increasing cytotoxicity ( Lo et al, 2011 ). The capsule is essential for resistance to phagocytic cells in various bacteria ( Simpson et al, 1987 ; Oliver, 2015 ; Yamazaki et al, 2019 ; Kashimoto et al, 2021 ). The environmental strain E4 and Δ rtxA were a low ability to proliferate in the subcutaneous tissues compared with WT ( Figure 5A ).…”

“…However, these models do not focus on proliferation mechanisms in the soft tissues. Hence, we had developed a wound infection model of V. vulnificus and used this model to select pathogenic factors and to evaluate pathogenic mechanisms in NSTI (Yamazaki et al, 2019(Yamazaki et al, , 2020Kashimoto et al, 2021). However, there are no reports of detailed analysis of the progressive pathology in wound infection using in vivo models.…”

“…It does this through multifunctional autoprocessing repeats-in toxin (MARTX) and encapsulation, which helps resist phagocytic cells ( Lo et al, 2011 ; Roje et al, 2011 ; Jeong and Satchell, 2012 ). Vibrio vulnificus strains isolated from the environment have rtxA , which encodes MARTX but exhibits a translucent colony, meaning it is not encapsulated in contrast to clinical strains that are encapsulated ( Simpson et al, 1987 ; Oliver, 2015 ; Yamazaki et al, 2019 ; Kashimoto et al, 2021 ).…”