TY  - JOUR
AU  - Kever, Larissa
AU  - Hünnefeld, Max
AU  - Brehm, Jannis
AU  - Heermann, Ralf
AU  - Frunzke, Julia
TI  - Identification of Gip as a novel phage‐encoded gyrase inhibitor protein of Corynebacterium glutamicum
JO  - Molecular microbiology
VL  - 116
IS  - 5
SN  - 1365-2958
CY  - Oxford [u.a.]
PB  - Wiley-Blackwell
M1  - FZJ-2021-03707
SP  - 1268 - 1280
PY  - 2021
N1  - Biotechnologie 1
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:34536319
UR  - <Go to ISI:>//WOS:000701241500001
DO  - DOI:10.1111/mmi.14813
UR  - https://juser.fz-juelich.de/record/897245
ER  -