The Role of Autophagy during Group B Streptococcus Infection of Blood-Brain Barrier Endothelium

Cutting, Andrew S.; Rosario, Yvette Del; Mu, Rong; Rodriguez, Anthony; Till, Andreas; Subramani, Suresh; Gottlieb, Roberta A.; Doran, Kelly S.

doi:10.1074/jbc.m114.588657

Cited by 49 publications

(49 citation statements)

References 81 publications

(81 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, one study conducted by Eugenin et al examined the role of human immunodeficiency virus (HIV)-infected astrocytes in BBB disruption using a 2D Transwell model [201]. Another study described by Cutting et al examined selective autophagy activities in host defenses after BBB penetration of Group B Streptococcus (GBS), one of the leading meningeal pathogens, both in a 2D model and in vivo [202]. However, although many studies have been carried out using different in vitro BBB models, few studies have used this advantageous technology for brain infection studies.…”

Section: Bbb-on-a-chipmentioning

confidence: 99%

“…One of the underlying reasons for their limited use in this area may be due to the toxicity that results from co-culturing brain endothelial cells with infectious pathogens. With this, Brown et al introduced a BBB-on-a-chip microfluidic device consisting of separate vascular and brain channels, separated by a porous PDMS membrane [202]. This not only enables cell-to-cell interaction between brain tissue cells, but also allows for the independent perfusion of both compartments.…”

Section: Bbb-on-a-chipmentioning

confidence: 99%

See 1 more Smart Citation

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

Shi

Wang

et al. 2019

Biomaterials

View full text Add to dashboard Cite

A B S T R A C TBacterial infections and antibiotic resistant bacteria have become a growing problem over the past decade. As a result, the Centers for Disease Control predict more deaths resulting from microorganisms than all cancers combined by 2050. Currently, many traditional models used to study bacterial infections fail to precisely replicate the in vivo bacterial environment. These models often fail to incorporate fluid flow, bio-mechanical cues, intercellular interactions, host-bacteria interactions, and even the simple inclusion of relevant physiological proteins in culture media. As a result of these inadequate models, there is often a poor correlation between in vitro and in vivo assays, limiting therapeutic potential. Thus, the urgency to establish in vitro and ex vivo systems to investigate the mechanisms underlying bacterial infections and to discover new-age therapeutics against bacterial infections is dire. In this review, we present an update of current in vitro and ex vivo models that are comprehensively changing the landscape of traditional microbiology assays. Further, we provide a comparative analysis of previous research on various established organ-disease models. Lastly, we provide insight on future techniques that may more accurately test new formulations to meet the growing demand of antibiotic resistant bacterial infections. Lack of adequate model systemsCommonly, a variety of inconsistent, in vitro and in vivo models have been progressively utilized for antibiotic/drug development and pathophysiological studies. These systems range from simple in vitro models using microtiter plate assays and flow cells to more complex in https://doi.

show abstract

Section: Bbb-on-a-chipmentioning

confidence: 99%

Section: Bbb-on-a-chipmentioning

confidence: 99%

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

Shi

Wang

et al. 2019

Biomaterials

View full text Add to dashboard Cite

show abstract

“…In addition, infection of macrophages and epithelial cells with B. pseudomallei or Burkholderia cenocepacia leads to downregulation of certain autophagy genes, resulting in decreased levels of autophagy[39,40]. Group B streptococcus (GBS) induces autophagy during infection of EC, but still resides primarily in single membrane-bound compartments, suggesting that GBS evades targeting to autophagosomes[41]. Streptococcus suis blocks xenophagy during infection of macrophages by secreting superoxide dismutase to scavenge cellular ROS[42].…”

Section: Xenophagy Beyond M Tuberculosis As Revealed By Cell Culturementioning

confidence: 99%

“…The use of rapamycin in cell cultures has been shown to decrease the survival of various intracellular bacterial pathogens including GBS[41], P. aeruginosa [103], Salmonella [44], B. pseudomallei [104], and M. tuberculosis [105]. However, the differences in bacterial burden tend to be less than 2.5 fold[41,44,103,104]. In addition, a recent study found that in macrophages coinfected with HIV and M. tuberculosis , stimulation of autophagy with rapamycin actually led to increased M. tuberculosis survival[106].…”

Section: Targeting Autophagy As a Host-directed Therapy To Treat Bactmentioning

confidence: 99%

Bacterial Pathogens versus Autophagy: Implications for Therapeutic Interventions

Kimmey

Stallings

2016

Trends in Molecular Medicine

131

117

View full text Add to dashboard Cite

Research in recent years has focused significantly on the role of selective macroautophagy in targeting intracellular pathogens for lysosomal degradation, a process termed xenophagy. In this review we evaluate the proposed roles for xenophagy in controlling bacterial infection, highlighting the concept that successful pathogens have evolved ways to subvert or exploit this defense, minimizing the actual effectiveness of xenophagy in innate immunity. Instead, studies in animal models have revealed that autophagy-associated proteins often function outside of xenophagy to influence bacterial pathogenesis. In light of current efforts to manipulate autophagy and the development of host-directed therapies to fight bacterial infections, we also discuss the implications stemming from the complicated relationship that exists between autophagy and bacterial pathogens.

show abstract

“…In another example, intracellular Group B Streptococcus β-hemolysin/cytolysin (β-h/c) triggers autophagy in ECs, which in turn kills the majority of the internalized bacteria [27]. Thus, in both of these examples ECs are able to fight back with autophagy, but not effectively enough to completely prevent disease.…”

Section: Autophagy: Endothelial Cells Fight Backmentioning

confidence: 99%

Bacteria and endothelial cells: a toxic relationship

Lubkin

Torres

2017

Current Opinion in Microbiology

View full text Add to dashboard Cite

Pathogenic bacteria use the bloodstream as a highway for getting around the body, and thus have to find ways to enter and exit through the endothelium. Many bacteria approach this problem by producing toxins that can breach the endothelial barrier through diverse creative mechanisms, including directly killing endothelial cells (ECs), weakening the cytoskeleton within ECs, and breaking the junctions between ECs. Toxins can also modulate the immune response by influencing endothelial biology, and can modulate endothelial function by influencing the response of leukocytes. Understanding these interactions, in both the in vitro and in vivo contexts, is of critical importance for designing new therapies for sepsis and other severe bacterial diseases.

show abstract

The Role of Autophagy during Group B Streptococcus Infection of Blood-Brain Barrier Endothelium

Cited by 49 publications

References 81 publications

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

Bacterial Pathogens versus Autophagy: Implications for Therapeutic Interventions

Bacteria and endothelial cells: a toxic relationship

Contact Info

Product

Resources

About