%0 Journal Article
%A Kever, Larissa
%A Hünnefeld, Max
%A Brehm, Jannis
%A Heermann, Ralf
%A Frunzke, Julia
%T Identification of Gip as a novel phage‐encoded gyrase inhibitor protein of Corynebacterium glutamicum
%J Molecular microbiology
%V 116
%N 5
%@ 1365-2958
%C Oxford [u.a.]
%I Wiley-Blackwell
%M FZJ-2021-03707
%P 1268 - 1280
%D 2021
%Z Biotechnologie 1
%X By targeting key regulatory hubs of their host, bacteriophages represent a powerful source for the identification of novel antimicrobial proteins. Here, a screening of small cytoplasmic proteins encoded by the CGP3 prophage of Corynebacterium glutamicum resulted in the identification of the gyrase-inhibiting protein Cg1978, termed Gip. Pull-down assays and surface plasmon resonance revealed a direct interaction of Gip with the gyrase subunit A (GyrA). The inhibitory activity of Gip was shown to be specific to the DNA gyrase of its bacterial host C. glutamicum. Overproduction of Gip in C. glutamicum resulted in a severe growth defect as well as an induction of the SOS response. Furthermore, reporter assays revealed an RecA-independent induction of the cryptic CGP3 prophage, most likely caused by topological alterations. Overexpression of gip was counteracted by an increased expression of gyrAB and a reduction of topA expression at the same time, reflecting the homeostatic control of DNA topology. We postulate that the prophage-encoded Gip protein plays a role in modulating gyrase activity to enable efficient phage DNA replication. A detailed elucidation of the mechanism of action will provide novel directions for the design of drugs targeting DNA gyrase.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:34536319
%U <Go to ISI:>//WOS:000701241500001
%R 10.1111/mmi.14813
%U https://juser.fz-juelich.de/record/897245