Stimulation of autophagy suppresses the intracellular survival of Burkholderia pseudomallei in mammalian cell lines.

Abstract:

:Burkholderia pseudomallei is the causative agent of melioidosis, a tropical infection of humans and other animals. The bacterium is an intracellular pathogen that can escape from endosomes into the host cytoplasm, where it replicates and infects adjacent cells. We investigated the role played by autophagy in the intracellular survival of B. pseudomallei in phagocytic and non-phagocytic cell lines. Autophagy was induced in response to B. pseudomallei invasion of murine macrophage (RAW 264.7) cells and a proportion of the bacteria co-localized with the autophagy effector protein LC3, a marker for autophagosome formation. Pharmacological stimulation of autophagy in RAW 264.7 and murine embryonic fibroblast (MEF) cell lines resulted in increased co-localization of B. pseudomallei with LC3 while basal levels of co-localization could be abrogated using inhibitors of the autophagic pathway. Furthermore, induction of autophagy decreased the intracellular survival of B. pseudomallei in these cell lines, but bacterial survival was not affected in MEF cell lines deficient in autophagy. Treatment of infected macrophages with chloramphenicol increased the proportion of bacteria within autophagosomes indicating that autophagic evasion is an active process relying on bacterial protein synthesis. Consistent with this hypothesis, we identified a B. pseudomallei type III secreted protein, BopA, which plays a role in mediating bacterial evasion of autophagy. We conclude that the autophagic pathway is a component of the innate defense system against invading B. pseudomallei, but which the bacteria can actively evade. However, when autophagy is pharmacologically induced using rapamycin, bacteria are actively sequestered in autophagosomes, ultimately decreasing their survival.

journal_name

Autophagy

journal_title

Autophagy

authors

Cullinane M,Gong L,Li X,Lazar-Adler N,Tra T,Wolvetang E,Prescott M,Boyce JD,Devenish RJ,Adler B

doi

10.4161/auto.6246

subject

Has Abstract

pub_date

2008-08-01 00:00:00

pages

744-53

issue

6

eissn

1554-8627

issn

1554-8635

pii

6246

journal_volume

4

pub_type

杂志文章
  • Autophagy-mediated regulation of macrophages and its applications for cancer.

    abstract::Autophagy is a highly conserved homeostatic pathway that plays an important role in tumor development and progression by acting on cancer cells in a cell-autonomous mechanism. However, the solid tumor is not an island, but rather an ensemble performance that includes nonmalignant stromal cells, such as macrophages. A ...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.4161/auto.26927

    authors: Chen P,Cescon M,Bonaldo P

    更新日期:2014-02-01 00:00:00

  • RUBCN/rubicon and EGFR regulate lysosomal degradative processes in the retinal pigment epithelium (RPE) of the eye.

    abstract::Macroautophagy/autophagy is an intracellular stress survival and recycling system whereas phagocytosis internalizes material from the extracellular milieu; yet, both pathways utilize lysosomes for cargo degradation. Whereas autophagy occurs in all cells, phagocytosis is performed by cell types such as macrophages and ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2017.1380124

    authors: Muniz-Feliciano L,Doggett TA,Zhou Z,Ferguson TA

    更新日期:2017-01-01 00:00:00

  • The role of mannose-6-phosphate receptor and autophagy in influencing the outcome of combination therapy.

    abstract::Combining two different treatment modalities for targeting malignancies is gaining importance, with preclinical/clinical results indicating higher success rates in eradicating tumors or having longer remission periods. A better understanding of the synergy between the treatments helps in optimizing the dose and time o...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.23485

    authors: Ramakrishnan R,Gabrilovich DI

    更新日期:2013-04-01 00:00:00

  • The ULK1 complex: sensing nutrient signals for autophagy activation.

    abstract::The Atg1/ULK1 complex plays a central role in starvation-induced autophagy, integrating signals from upstream sensors such as MTOR and AMPK and transducing them to the downstream autophagy pathway. Much progress has been made in the last few years in understanding the mechanisms by which the complex is regulated throu...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.4161/auto.23323

    authors: Wong PM,Puente C,Ganley IG,Jiang X

    更新日期:2013-02-01 00:00:00

  • Autophagic degradation of SQSTM1 inhibits ovarian cancer motility by decreasing DICER1 and AGO2 to induce MIRLET7A-3P.

    abstract::The relationship between macroautophagy/autophagy and miRNA in regulating cancer cell motility is not clearly delineated. Here, we found that induction of BECN1-dependent or -independent autophagy decreased ubiquitin-binding proteins SQSTM1/p62 and CALCOCO2/NDP52. Downregulation of SQSTM1 (but not CALCOCO2) led to a d...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2018.1501135

    authors: Liao CC,Ho MY,Liang SM,Liang CM

    更新日期:2018-01-01 00:00:00

  • Facilitated ethanol metabolism promotes cardiomyocyte contractile dysfunction through autophagy in murine hearts.

    abstract::Chronic drinking leads to myocardial contractile dysfunction where ethanol metabolism plays an essential role. Acetaldehyde, the main ethanol metabolite, mediates alcohol-induced cell injury although the underlying mechanism is still elusive. This study was designed to examine the mechanism involved in accelerated eth...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.18997

    authors: Guo R,Hu N,Kandadi MR,Ren J

    更新日期:2012-04-01 00:00:00

  • Unsaturation, curvature and charge: effects of membrane parameters on PIK3C3/VPS34-containing complexes.

    abstract::Phosphatidylinositol-3-phosphate (PtdIns3P) is essential for generating autophagosomes and regulating endocytic trafficking. Recently, we have shown that the activities of human PIK3C3/VPS34-containing complexes I and II, which synthesize PtdIns3P, are greatly affected by three membrane physicochemical parameters: lip...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2021.1872190

    authors: Ohashi Y,Tremel S,Williams RL

    更新日期:2021-01-15 00:00:00

  • Dual inhibition of autophagy and the AKT pathway in prostate cancer.

    abstract::Genetic inactivation of PTEN through either gene deletion or mutation is common in metastatic prostate cancer, leading to activation of the phosphoinositide 3-kinase (PI3K-AKT) pathway, which is associated with poor clinical outcomes. The PI3K-AKT pathway plays a central role in various cellular processes supporting c...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.24921

    authors: Lamoureux F,Zoubeidi A

    更新日期:2013-07-01 00:00:00

  • DJ-1 regulation of mitochondrial function and autophagy through oxidative stress.

    abstract::The dysregulation of mitochondrial function has been implicated in the pathogenesis of Parkinson disease. Mutations in the parkin, PINK1 and DJ-1 genes all result in recessive parkinsonism. Although the protein products of these genes have not been fully characterized, it has been established that all three contribute...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.7.5.14684

    authors: McCoy MK,Cookson MR

    更新日期:2011-05-01 00:00:00

  • Retromer regulates the lysosomal clearance of MAPT/tau.

    abstract::The macroautophagy/autophagy-lysosome axis enables the clearance and degradation of cytoplasmic components including protein aggregates, damaged organelles and invading pathogens. Protein aggregation and lysosomal system dysfunction in the brain are common features of several late-onset neurological disorders includin...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2020.1821545

    authors: Carosi JM,Hein LK,van den Hurk M,Adams R,Milky B,Singh S,Bardy C,Denton D,Kumar S,Sargeant TJ

    更新日期:2020-09-22 00:00:00

  • Role of actin in shaping autophagosomes.

    abstract::One of the main unanswered questions regarding the early steps of macroautophagy/autophagy is the mechanism of membrane-modeling events required for autophagosome formation. Three independent studies have recently revealed an actin cytoskeleton involvement in this process, providing significant details regarding the r...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2016.1236877

    authors: Zientara-Rytter K,Subramani S

    更新日期:2016-12-01 00:00:00

  • Autophagy, Inflammation, and Metabolism (AIM) Center in its second year.

    abstract::The NIH-funded center for autophagy research named Autophagy, Inflammation, and Metabolism (AIM) Center of Biomedical Research Excellence, located at the University of New Mexico Health Science Center is now completing its second year as a working center with a mission to promote autophagy research locally, nationally...

    journal_title:Autophagy

    pub_type: 历史文章,杂志文章

    doi:10.1080/15548627.2019.1634444

    authors: Deretic V,Prossnitz E,Burge M,Campen MJ,Cannon J,Liu KJ,Liu M,Hall P,Sklar LA,Allers L,Mariscal L,Garcia SA,Weaver J,Baehrecke EH,Behrends C,Cecconi F,Codogno P,Chen GC,Elazar Z,Eskelinen EL,Fourie B,Gozuacik D

    更新日期:2019-10-01 00:00:00

  • Members of the autophagy class III phosphatidylinositol 3-kinase complex I interact with GABARAP and GABARAPL1 via LIR motifs.

    abstract::Autophagosome formation depends on a carefully orchestrated interplay between membrane-associated protein complexes. Initiation of macroautophagy/autophagy is mediated by the ULK1 (unc-51 like autophagy activating kinase 1) protein kinase complex and the autophagy-specific class III phosphatidylinositol 3-kinase compl...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2019.1581009

    authors: Birgisdottir ÅB,Mouilleron S,Bhujabal Z,Wirth M,Sjøttem E,Evjen G,Zhang W,Lee R,O'Reilly N,Tooze SA,Lamark T,Johansen T

    更新日期:2019-08-01 00:00:00

  • Longevity-relevant regulation of autophagy at the level of the acetylproteome.

    abstract::The acetylase inhibitor, spermidine and the deacetylase activator, resveratrol, both induce autophagy and prolong life span of the model organism Caenorhabditis elegans in an autophagydependent fashion. Based on these premises, we investigated the differences and similarities in spermidine and resveratrol-induced auto...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.7.6.15191

    authors: Mariño G,Morselli E,Bennetzen MV,Eisenberg T,Megalou E,Schroeder S,Cabrera S,Bénit P,Rustin P,Criollo A,Kepp O,Galluzzi L,Shen S,Malik SA,Maiuri MC,Horio Y,López-Otín C,Andersen JS,Tavernarakis N,Madeo F,Kroemer G

    更新日期:2011-06-01 00:00:00

  • Impaired mitophagy at the heart of injury.

    abstract::Recent publications link mitophagy mediated by PINK1 and Parkin with cardioprotection and attenuation of inflammation and cell death. The field is in need of methods to monitor mitochondrial turnover in vivo to support the development of new therapies targeting mitochondrial turnover. ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.7.12.18175

    authors: Gottlieb RA,Mentzer RM Jr,Linton PJ

    更新日期:2011-12-01 00:00:00

  • Parkinsonian toxin-induced oxidative stress inhibits basal autophagy in astrocytes via NQO2/quinone oxidoreductase 2: Implications for neuroprotection.

    abstract::Oxidative stress (OS) stimulates autophagy in different cellular systems, but it remains controversial if this rule can be generalized. We have analyzed the effect of chronic OS induced by the parkinsonian toxin paraquat (PQ) on autophagy in astrocytoma cells and primary astrocytes, which represent the first cellular ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2015.1058683

    authors: Janda E,Lascala A,Carresi C,Parafati M,Aprigliano S,Russo V,Savoia C,Ziviani E,Musolino V,Morani F,Isidoro C,Mollace V

    更新日期:2015-01-01 00:00:00

  • Context effect: microRNA-10b in cancer cell proliferation, spread and death.

    abstract::Single microRNA (miRNA) can regulate expression of several or multiple principal targets in a specific microenvironment. In different cellular contexts, the same miRNA may exhibit diverse functions, depending on the repertoire and stoichiometry of its direct mRNA targets. For instance, in breast cancer, microRNA-10b (...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.7.11.17371

    authors: Gabriely G,Teplyuk NM,Krichevsky AM

    更新日期:2011-11-01 00:00:00

  • Increased expression of ATG genes during nonfeeding periods in the tick Haemaphysalis longicornis.

    abstract::Ticks are long-lived hematophagous arthropods and have tolerance to starvation. They can survive without food during the host-seeking period for several months to years. To understand how ticks obtain energy over a long period of non-feeding (starvation), we focused on autophagy, a crucial proteolysis system via the l...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.4.11668

    authors: Umemiya-Shirafuji R,Matsuo T,Liao M,Boldbaatar D,Battur B,Suzuki H,Fujisaki K

    更新日期:2010-05-01 00:00:00

  • How to interpret LC3 immunoblotting.

    abstract::Microtubule-associated protein light chain 3 (LC3) is now widely used to monitor autophagy. One approach is to detect LC3 conversion (LC3-I to LC3-II) by immunoblot analysis because the amount of LC3-II is clearly correlated with the number of autophagosomes. However, LC3-II itself is degraded by autophagy, making int...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.4161/auto.4600

    authors: Mizushima N,Yoshimori T

    更新日期:2007-11-01 00:00:00

  • Beyond autophagy: the role of UVRAG in membrane trafficking.

    abstract::Autophagy is a lysosome-directed membrane trafficking event for the degradation of cytoplasmic components, including organelles. The past few years have seen a great advance in our understanding of the cellular machinery of autophagosome biogenesis, the hallmark of autophagy. However, our global understanding of autop...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6496

    authors: Liang C,Sir D,Lee S,Ou JH,Jung JU

    更新日期:2008-08-01 00:00:00

  • Early alterations of autophagy in Huntington disease-like mice.

    abstract::In a recent study, we reported in vivo evidence of early and sustained alterations of autophagy markers in a novel knock-in mouse model of Huntington disease (HD). The novel model is derived from selective breeding of HdhQ150 knock-in mice to generate mice with ~200 CAG/polyglutamine repeats (HdhQ200). HdhQ200 knockin...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.8.13617

    authors: Heng MY,Detloff PJ,Paulson HL,Albin RL

    更新日期:2010-11-01 00:00:00

  • The MAPK1/3 pathway is essential for the deregulation of autophagy observed in G2019S LRRK2 mutant fibroblasts.

    abstract::The link between the deregulation of autophagy and cell death processes can be essential in the development of several neurodegenerative diseases, such as Parkinson disease (PD). However, the molecular mechanism of deregulation of this degradative process in PD patients is unknown. The leucine-rich repeat kinase 2 (LR...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.21270

    authors: Bravo-San Pedro JM,Gómez-Sánchez R,Niso-Santano M,Pizarro-Estrella E,Aiastui-Pujana A,Gorostidi A,Climent V,López de Maturana R,Sanchez-Pernaute R,López de Munain A,Fuentes JM,González-Polo RA

    更新日期:2012-10-01 00:00:00

  • Progesterone receptor membrane component 1/Sigma-2 receptor associates with MAP1LC3B and promotes autophagy.

    abstract::Autophagy resembles a recycling process in which proteins, organelles, or regions of the cytoplasm are enveloped and degraded. We have found that two of the central autophagy proteins, MAP1LC3 (microtubule-associated protein 1 light chain 3, also described as LC3) and UVRAG (UV radiation resistance associated/UV radia...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.25889

    authors: Mir SU,Schwarze SR,Jin L,Zhang J,Friend W,Miriyala S,St Clair D,Craven RJ

    更新日期:2013-10-01 00:00:00

  • Essential control of mitochondrial morphology and function by chaperone-mediated autophagy through degradation of PARK7.

    abstract::As a selective degradation system, chaperone-mediated autophagy (CMA) is essential for maintaining cellular homeostasis and survival under stress conditions. Increasing evidence points to an important role for the dysfunction of CMA in the pathogenesis of Parkinson disease (PD). However, the mechanisms by which CMA re...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2016.1179401

    authors: Wang B,Cai Z,Tao K,Zeng W,Lu F,Yang R,Feng D,Gao G,Yang Q

    更新日期:2016-08-02 00:00:00

  • Critical role of autophage in ischemia/reperfusion injury to aged livers.

    abstract::A steady increase in life expectancy has resulted in an equivalent increase in elderly patients who are more susceptible to diseases than young patients. In a recent study, we found that in both in vitro and in vivo models of ischemia/reperfusion (I/R), a loss of ATG4B is causatively associated with the increased sens...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.8.1.18391

    authors: Wang JH,Behrns KE,Leeuwenburgh C,Kim JS

    更新日期:2012-01-01 00:00:00

  • HIF1A Alleviates compression-induced apoptosis of nucleus pulposus derived stem cells via upregulating autophagy.

    abstract::Intervertebral disc degeneration (IDD) is the primary pathological mechanism that underlies low back pain. Overloading-induced cell death, especially endogenous stem cell death, is the leading factor that undermines intrinsic repair and aggravates IDD. Previous research has separately studied the effect of oxygen conc...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2021.1872227

    authors: He R,Wang Z,Cui M,Liu S,Wu W,Chen M,Wu Y,Qu Y,Lin H,Chen S,Wang B,Shao Z

    更新日期:2021-01-18 00:00:00

  • The NEDD4-USP13 axis facilitates autophagy via deubiquitinating PIK3C3.

    abstract::Macroautophagy/autophagy, an evolutionarily conserved eukaryotic bioprocess, plays an important role in the bulk degradation of intracellular macromolecules, organelles, and invading pathogens. PIK3C3/VPS34 (phosphatidylinositol 3-kinase catalytic subunit type 3) functions as a key protein in autophagy initiation and ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2020.1743071

    authors: Xie W,Jin S,Cui J

    更新日期:2020-06-01 00:00:00

  • TNFAIP3-DEPTOR complex regulates inflammasome secretion through autophagy in ankylosing spondylitis monocytes.

    abstract::Ankylosing spondylitis (AS) is a chronic autoimmune inflammatory disease with severe inflammatory symptoms in the axial skeleton. The cause of ankylosing spondylitis is unknown. TNFAIP3, also named A20, uses ubiquitin-related functions to regulate immune activation, deficiency of which is highly related to autoimmune ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2018.1458804

    authors: Zhai Y,Lin P,Feng Z,Lu H,Han Q,Chen J,Zhang Y,He Q,Nan G,Luo X,Wang B,Feng F,Liu F,Chen Z,Zhu P

    更新日期:2018-01-01 00:00:00

  • LAMP2A as a therapeutic target in Parkinson disease.

    abstract::Abnormal aggregation of SNCA/?-synuclein plays a crucial role in Parkinson disease (PD) pathogenesis. SNCA levels determine its toxicity, and its accumulation, even to a small extent, may be a risk factor for neurodegeneration. One of the main pathways for SNCA degradation is chaperone-mediated autophagy (CMA), a sele...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.26451

    authors: Xilouri M,Brekk OR,Kirik D,Stefanis L

    更新日期:2013-12-01 00:00:00

  • Autosomal dominant retinitis pigmentosa-associated gene PRPF8 is essential for hypoxia-induced mitophagy through regulating ULK1 mRNA splicing.

    abstract::Aged and damaged mitochondria can be selectively degraded by specific autophagic elimination, termed mitophagy. Defects in mitophagy have been increasingly linked to several diseases including neurodegenerative diseases, metabolic diseases and other aging-related diseases. However, the molecular mechanisms of mitophag...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2018.1501251

    authors: Xu G,Li T,Chen J,Li C,Zhao H,Yao C,Dong H,Wen K,Wang K,Zhao J,Xia Q,Zhou T,Zhang H,Gao P,Li A,Pan X

    更新日期:2018-01-01 00:00:00