Growth phase-dependent production of a toxic metalloprotease by Vibrio vulnificus

Vibrio vulnificus, a ubiquitous estuarine bacterium, is divided into two groups based on the virulence potential. Group 1 is a causative agent of human fatal septicemia, which is characterized by edematous and hemorrhagic secondary skin lesions on the limbs. This human pathogen secretes a toxic metalloprotease as an important virulence determinant. The protease can evoke the skin damage through enhancement of the vascular permeability and destruction of the capillaries. Group 2 is an etiological agent of epizooticus in the cultured eels. Significant levels of metalloprotease as well as autoinducer, a well-known signal molecule of cell-density dependent regulatory system for production of virulence determinants, were found to be secreted by both the groups at early stationary phase but not middle logarithmic phase when the bacteria were cultivated at 25°C. Expression of the protease gene also was found to be increased several times at the stationary phase. Therefore, the autoinducer molecules that had accumulated might have accelerated the expression of the protease gene. In contrast, when cultivated at 37°C, far less amounts of the protease and autoinducer were produced even at the stationary phase. Most patients suffering from V. vulnificus septicemia have underlying diseases causing elevation of the serum iron level. When incubated in human serum supplemented with ferric chloride at 37°C, only Group 1 V. vulnificus showed steady bacterial multiplication and protease production but secretion of significant level of autoinducer could not be detected. Hence, the protease production by Group 1 V. vulnificus in human serum containing ferric ion is also dependent on the bacterial growth; however, protease production in this condition does not require the accumulation of the autoinducer.