Abstract

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.

Highlights

  • Necrotizing soft-tissue infections (NSTIs) such as severe soft tissue necrosis and sepsis are the most dramatically progressing bacterial infections

  • Despite the fact that lesions in NSTI progress dramati­ cally from the epidermis through complex tissues such as dermis, hypodermis, subcutaneous fat, fascia, muscle, and into the systemic circulation [1,2,3,4], the pathogenic factors that cause the rapid expansion of these infections in patients have not been elucidated

  • We showed here for the first time that the chemotaxis of V. vulnificus was essential for rapid bacterial spread from the infection site to a deep layer of muscle and systemic circulation through complex tissues by appropriately switching from smooth swimming to turn and from swimming to swarming in wound infection

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Summary

Introduction

Necrotizing soft-tissue infections (NSTIs) such as severe soft tissue necrosis and sepsis are the most dramatically progressing bacterial infections. V. vulinificus NSTI occurs via exposure through an open wound (wound infection) or via the ingestion of raw seafood (primary septicemia) [4,5,6,7,8,9]. This pathogen lives in warmish, brackish water regions, and wound infections are increasing owing to rising seawater tem­ peratures caused by climate change [5,8,9]. The factors contributing to the rapid expansion of the necrotic lesion have not been clarified

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