AUTHOR=Spidlova Petra , Sokolova Eliska , Pavlik Pavla 

TITLE=Bacteriophage SPO1 protein Gp46 suppresses functions of HU protein in Francisella tularensis

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1330109

DOI=10.3389/fmicb.2023.1330109

ISSN=1664-302X

ABSTRACT=<p>The nucleoid-associated protein HU is a common bacterial transcription factor, whose role in pathogenesis and virulence has been described in many bacteria. Our recent studies showed that the HU protein is an indispensable virulence factor in the human pathogenic bacterium <italic>Francisella tularensis</italic>, a causative agent of tularemia disease, and that this protein can be a key target in tularemia treatment or vaccine development. Here, we show that <italic>Francisella</italic> HU protein is inhibited by Gp46, a protein of <italic>Bacillus subtilis</italic> bacteriophage SPO1. We predicted that Gp46 could occupy the <italic>F. tularensis</italic> HU protein DNA binding site, and subsequently confirmed the ability of Gp46 to abolish the DNA-binding capacity of HU protein. Next, we showed that the growth of <italic>Francisella</italic> wild-type strain expressing Gp46 <italic>in trans</italic> corresponded to that of a deletion mutant strain lacking the HU protein. Similarly, the efficiency of intracellular proliferation in mouse macrophages resembled that of the deletion mutant strain, but not that of the wild-type strain. These results, in combination with findings from a recent study on Gp46, enabled us to confirm that Gp46 could be a universal inhibitor of HU proteins among bacterial species.</p>