Glutamate Limitation, BvgAS Activation and (p)ppGpp Regulate the Expression of the Bordetella pertussis Type 3 Secretion System.

Bordetella pertussis is a bacterium that is considered to be highly adapted to humans and it has not been isolated from the environment. As this bacterium does not utilize sugars, the abundant supply of glutamate in Stainer Scholte (SS) medium enables B. pertussis to grow efficiently in liquid culture in vitro, and as such, SS medium is a popular choice for laboratory experiments. However, the concentration of glutamate in the in vivo niche of B. pertussis is quite low. We investigated the bacterial response to low concentrations of glutamate to elucidate bacterial physiology via expression of the T3SS (type 3 secretion system), and discuss its relationship to the Bvg-mode in which the two-component regulator of pathogenesis (BvgAS) is activated.Glutamate limitation induced the expression of both the T3SS apparatus and effector genes at the transcriptional level. (p)ppGpp, a modulator of the stringent response, was necessary for maximum expression of the T3SS genes. These observations indicate that expression of the T3SS is managed by nutrient starvation. In addition, the autoaggregation ability was high in the absence of glutamate and no autoaggregation was observed in glutamate replete medium. Taken together, glutamate limited conditions in Bvg+ mode elicit high expression of T3SS genes in B. pertussis and promotes its sessile form.
Bordetella pertussis is a highly contagious pathogen that causes respiratory infectious disease. In spite of increasing vaccination, the number of patients with pertussis is increasing.The proteins produced in vivo are often different from the protein profile under laboratory conditions and therefore the development of conditions reflecting the host environment is important to understand native bacterial behavior. In the present study, we examined the effect of glutamate limitation, as its concentration in vivo is much lower than that in the culture medium currently used for B. pertussis experiments. As predicted, the type 3 secretion system (T3SS) was induced by glutamate limitation. These results are suggestive of the importance of regulation by nutrient conditions and in the pathogenicity of B. pertussis.

Authors:Hanawa T1, Kamachi K2, Yonezawa H3, Fukutomi T4, Kawakami H5, Kamiya S3.
Journal:J Bacteriol. 2015