AUTHOR=Zhang Jing-Ren 

TITLE=The capBCA Locus is Required for Intracellular Growth of Francisella tularensis LVS

JOURNAL=Frontiers in Microbiology

VOLUME=2

YEAR=2011

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2011.00083

DOI=10.3389/fmicb.2011.00083

ISSN=1664-302X

ABSTRACT=<p><italic>Francisella tularensis</italic> is the causative agent of tularemia and a category A bioterrorism agent. The molecular basis for the extreme virulence of <italic>F. tularensis</italic> remains unclear. Our recent study found that <italic>capBCA</italic>, three neighboring genes, are necessary for the infection of <italic>F. tularensis</italic> live vaccine strain (LVS) in a respiratory infection mouse model. We here show that the <italic>capBCA</italic> genes are necessary for <italic>in vivo</italic> growth of <italic>F. tularensis</italic> LVS in the lungs, spleens, and livers of BALB/c mice. Unmarked deletion of <italic>capBCA</italic> in type A strain Schu S4 resulted in significant attenuation in virulence although the level of the attenuation in Schu S4 was much less profound than in LVS. We further demonstrated that CapB protein is produced at a low level under the <italic>in vitro</italic> culture conditions, and <italic>capB</italic> alone is necessary for <italic>in vivo</italic> growth of <italic>F. tularensis</italic> LVS in the lungs of BALB/c mice. Finally, deletional mutations in <italic>capB</italic> alone or <italic>capBCA</italic> significantly impaired intracellular growth of <italic>F. tularensis</italic> LVS in cultured macrophages, thus suggesting that the <italic>capBCA</italic> genes are necessary for intracellular adaptation of <italic>F. tularensis</italic>. The requirement of this gene locus in intracellular adaption at least in part explains the significant attenuation of <italic>F. tularensis capBCA</italic> mutants in virulence.</p>