Critical role of bacterial isochorismatase in the autophagic process induced byAcinetobacter baumanniiin mammalian cells

Abstract

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.

A Novel PhoP/PhoQ Regulation Pathway Modulates the Survival of Extraintestinal Pathogenic Escherichia coli in Macrophages

“…PhoP/PhoQ-HlyF pathway promoted the escape of ExPEC from phagolysosomes and entry into macrophage cytosol, our studies showed that ExPEC activated macroautophagy ( 57 , 60 ), since immunofluorescence labeling study demonstrated LC3-labeled ExPEC-containing autophagosome colocalized with Ub, a tag for antibacterial autophagy to decorate cytosolic bacteria ( 36 , 61 ). The colocalization of LC3 with wild-type ExPEC and the mutants suggested that PhoP/PhoQ-HlyF pathway might promote the formation of ExPEC-containing autophagosome during its survival in macrophages.…”

“…During infection in the cytosol, pathogens induce and activate macroautophagy (microorganism-specific autophagy), which is a critical innate immune response pathway to target and degrade intracellular microorganisms ( 57 – 59 ). The autophagosomes (the typical double membrane compartments) are established during the autophagy, and the autophagy adaptor protein LC3 and p62 act as the typical markers for bacteria-containing autophagosome formation ( 57 , 60 ). Extensive works confirm that the LC3-I is gradually converted into LC3-II during the activated autophagy in response to bacterial infection, and autophagy-recruited LC3-II colocalizes with bacteria-containing autophagosomes.…”

Biochanin a Enhances the Defense Against Salmonella enterica Infection Through AMPK/ULK1/mTOR-Mediated Autophagy and Extracellular Traps and Reversing SPI-1-Dependent Macrophage (MΦ) M2 Polarization

“…The intracellular bacterial killing assay was performed and evaluated by a gentamicin protection assay according to a previously published method (Wiedemann et al, 2012 ; Wang et al, 2016 ). The extracellular bacterial killing assay was performed and evaluated in accordance with a previously described method (Wang et al, 2016 ).…”

Microbial biodegradation of biuret: defining biuret hydrolases within the isochorismatase superfamily

“…Nicotinamidase/pyrazinamidase enzymes in Mycobacterium tuberculosis cleave the amide bond of pyrazinamide to produce the antibiotic pyrazinoic acid (Petrella et al ., ). Isochorismatases hydrolyze the activated vinyl ether bond of isochorismate in the shikimic acid pathway and function in phenazine production (Parsons et al ., ) and bacterial siderophore biosynthesis (Wang et al ., ). Other IHL superfamily subgroups perform more specialized functions, including the IHL streptothricin hydrolase in Streptomyces spp., which inactivates the antibiotic streptothricin via cleavage of the lactam ring (Hamano et al ., ).…”