Identifying the factors responsible for survival and virulence of Bacillus anthracis within the host is prerequisite for the development of
therapeutics against
anthrax. Host provides several stresses as well as many advantages to the invading pathogen.
Inorganic phosphate (Pi)
starvation within the host has been considered as one of the major contributing factors in the establishment of
infection by pathogenic microorganisms. Here, we report for the first time that Pi fluctuation encountered by B. anthracis at different stages of its life cycle within the host, contributes significantly in its pathogenesis. In this study, Pi
starvation was found to hasten the onset of
infection cycle by promoting spore germination. After germination, it was found to impede cell growth. In addition,
phosphate starved bacilli showed more
antibiotic tolerance. Interestingly,
phosphate starvation enhanced the pathogenicity of B. anthracis by augmenting its invasiveness in macrophages in vitro. B. anthracis grown under
phosphate starvation were also found to be more efficient in establishing lethal
infections in mouse model as well.
Phosphate starvation increased B. anthracis virulence by promoting the secretion of primary
virulence factors like protective
antigen (PA), lethal factor (LF) and
edema factor (EF). Thus, this study affirms that besides other host mediated factors,
phosphate limitation may also contribute B. anthracis for successfully establishing itself within the host. This study is a step forward in delineating its pathophysiology that might help in understanding the pathogenesis of
anthrax.