A recent study reported that Acinetobacter baumannii could induce
autophagy, but the recognition and clearance mechanism of intracytosolic A.
baumannii in the autophagic process and the molecular mechanism of
autophagy induced by the pathogen remains unknown. In this study, we first
demonstrated that invading A. baumannii induced a complete,
ubiquitin-mediated autophagic response that is dependent upon septins SEPT2 and SEPT9
in mammalian cells. We also demonstrated that autophagy induced by A.
baumannii was Beclin-1 dependent via the
AMPK/ERK/mammalian target of rapamycin pathway. Of interest, we found that the
isochorismatase mutant strain had significantly decreased siderophore-mediated ferric
iron acquisition ability and had a reduced the ability to induce autophagy. We
verified that isochorismatase was required for the recognition of intracytosolic
A. baumannii mediated by septin cages, ubiquitinated proteins,
and ubiquitin-binding adaptor proteins p62 and NDP52 in autophagic response. We also
confirmed that isochorismatase was required for the clearance of invading A.
baumannii by autophagy in vitro and in the mouse model
of infection. Together, these findings provide insight into the distinctive
recognition and clearance of intracytosolic A. baumannii by
autophagy in host cells, and that isochorismatase plays a critical role in the
A. baumannii–induced autophagic process.—Wang, Y.,
Zhang, K., Shi, X., Wang, C., Wang, F., Fan, J., Shen, F., Xu, J., Bao, W., Liu, M.,
Yu, L. Critical role of bacterial isochorismatase in the autophagic process induced
by Acinetobacter baumannii in mammalian cells.