Overexpressed Palladin Rescues Enteropathogenic E. coli (EPEC) Pedestal Lengths in ArpC2 Depleted Cells.

Enteropathogenic Escherichia coli (EPEC) causes diarrheal disease. Once ingested, these extracellular pathogens attach to the intestinal epithelial cells of their host, collapse the localized microvilli, and generate actin-rich structures within the host cells that are located beneath the attached bacteria, called "pedestals." Palladin is an actin-associated protein that cross-links and stabilizes actin filaments.

From anatomy to immunity in the gastrointestinal system.

The gastrointestinal system is classically known for its function in digesting food for nutrient uptake, but it plays a much larger role in the general health of organisms. Understanding the relationships between the gastrointestinal tract and inflammation, the nervous system, diseases caused through disregulation of molecular components as well as its association with beneficial and pathogenic microbes have been the focus of intense research over the many decades. In this Special Issue we delve into histological, molecular, and evolutionary aspects of gastrointestinal system components in healthy and diseased tissues, to give a broad perspective on the different organs that make-up this system.

Localization of host endocytic and actin-associated proteins during Shigella flexneri intracellular motility and intercellular spreading.

Shigella flexneri (S. flexneri), the causative agent of bacillary dysentery, uses an effector-mediated strategy to hijack host cells and cause disease. To propagate and spread within human tissues, S.

Ube2N is present and functions within listeria Actin-rich structures and lamellipodia: A localization and pharmacological inhibition study.

The actin cytoskeleton forms much of the structure needed for the intracellular motility of an assortment of microbes as well as entire cells. The co-factor to the ubiquitin conjugating enzyme Ube2N (Ube2V1) has been implicated in both cancer cell metastasis and lysine-63 ubiquitylation of β actin. As this protein complexes with Ube2N, we sought to investigate whether Ube2N itself was involved in actin-based events occurring during the Listeria monocytogenes infections as well as within motile whole cells.

mDia1 Assembles a Linear F-Actin Coat at Membrane Invaginations To Drive Listeria monocytogenes Cell-to-Cell Spreading.

Direct cell-to-cell spreading of Listeria monocytogenes requires the bacteria to induce actin-based finger-like membrane protrusions in donor host cells that are endocytosed through caveolin-rich membrane invaginations by adjacent receiving cells. An actin shell surrounds these endocytic sites; however, its structure, composition, and functional significance remain elusive. Here, we show that the formin mDia1, but surprisingly not the Arp2/3 complex, is enriched at the membrane invaginations generated by L.

Localization of alpha-actinin-4 during infections by actin remodeling bacteria.

Bacterial pathogens cause disease by subverting the structure and function of their target host cells. Several foodborne agents such as Listeria monocytogenes (L. monocytogenes), Shigella flexneri (S.

Distribution of PDLIM1 at actin-rich structures generated by invasive and adherent bacterial pathogens.

The enteric bacterial pathogens Listeria monocytogenes (Listeria) and enteropathogenic Escherichia coli (EPEC) remodel the eukaryotic actin cytoskeleton during their disease processes. Listeria generate slender actin-rich comet/rocket tails to move intracellularly, and later, finger-like membrane protrusions to spread amongst host cells. EPEC remain extracellular, but generate similar actin-rich membranous protrusions (termed pedestals) to move atop the host epithelia.

Listeria monocytogenes Exploits Host Caveolin for Cell-to-Cell Spreading.

moves from one cell to another using actin-rich membrane protrusions that propel the bacterium toward neighboring cells. Despite cholesterol being required for this transfer process, the precise host internalization mechanism remains elusive. Here, we show that caveolin endocytosis is key to this event as bacterial cell-to-cell transfer is severely impaired when cells are depleted of caveolin-1.

Klebsiella pneumoniae Redistributes Katanin Severing Proteins and Alters Astral Microtubules during Mitosis.

Klebsiella pneumoniae has become a growing concern within hospitals due to multidrug resistant strains and increasing mortality rates. Recently, we showed that at the subcellular level, K. pneumoniae compromises the integrity of the epithelia by disassembling the microtubule networks of cells through the actions of katanin microtubule severing proteins.

Edwardsiella induces microtubule-severing in host epithelial cells.

Edwardsiella bacteria cause economic losses to a variety of commercially important fish globally. Human infections are rare and result in a gastroenteritis-like illness. Because these bacteria are evolutionarily related to other Enterobacteriaceae and the host cytoskeleton is a common target of enterics, we hypothesized that Edwardsiella may cause similar phenotypes.

Distribution of CD147 During Enteropathogenic Escherichia coli and Salmonella enterica Serovar Typhimurium Infections.

Enteropathogenic Escherichia coli (EPEC) and Salmonella enterica serovar Typhimurium (S. Typhimurium) are highly infectious gastrointestinal human pathogens. These microbes inject bacterial-derived effector proteins directly into the host cell cytosol as part of their disease processes.

Listeria monocytogenes hijacks CD147 to ensure proper membrane protrusion formation and efficient bacterial dissemination.

Efficient cell-to-cell transfer of Listeria monocytogenes (L. monocytogenes) requires the proper formation of actin-rich membrane protrusions. To date, only the host proteins ezrin, the binding partner of ezrin, CD44, as well as cyclophilin A (CypA) have been identified as crucial components for L.

Klebsiella pneumoniae disassembles host microtubules in lung epithelial cells.

Klebsiella pneumoniae raises significant concerns to the health care industry as these microbes are the source of widespread contamination of medical equipment, cause pneumonia as well as other multiorgan metastatic infections and have gained multidrug resistance. Despite soaring mortality rates, the host cell alterations occurring during these infections remain poorly understood. Here, we show that during in vitro and in vivo K.

Calponins Are Recruited to Actin-Rich Structures Generated by Pathogenic Escherichia coli, Listeria, and Salmonella.

The ingestion of enteropathogenic Escherichia coli (EPEC), Listeria monocytogenes, or Salmonella enterica serovar Typhimurium leads to their colonization of the intestinal lumen, which ultimately causes an array of ailments ranging from diarrhea to bacteremia. Once in the intestines, these microbes generate various actin-rich structures to attach, invade, or move within the host intestinal epithelial cells. Although an assortment of actin-associated proteins has been identified to varying degrees at these structures, the localization of many actin stabilizing proteins have yet to be analyzed.

Hsc70 is a Component of Bacterially Generated Actin-Rich Structures: An Immunolocalization Study.

Enteropathogenic Escherichia coli (EPEC), Salmonella typhimurium, and Listeria monocytogenes usurp the actin cytoskeleton for their attachment, internalization and transport within and amongst infected cells. To try to gain a greater understanding of the molecular components utilized by these microbes during their infections we previously concentrated actin-rich structures generated during EPEC infections (called pedestals) and identified the heat shock cognate 70 protein (Hsc70) as a potential candidate. This multifunctional protein classically acts as a chaperone for the proper folding of a variety of proteins and is involved in uncoating clathrin from coated pits.

An Introduction to Actin and Actin-Rich Structures.

The actin cytoskeleton has long been recognized as a crucial sub-cellular filament system that is responsible for governing fundamental events ranging from cell division and muscle contraction to whole cell motility and the maintenance of tissue integrity. Consequently, it is not surprising that this network is the focus of over 100,000 different manuscripts. Alterations in the actin cytoskeleton lead to an assortment of diseases and serve as a target for a variety of pathogens.

Cyclophilin A Controls Salmonella Internalization Levels and is Present at E. coli Actin-Rich Pedestals.

Salmonella enterica serovar Typhimurium (S. Typhimurium), enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) commandeer the actin cytoskeleton of their host cells as a crucial step in their infectious processes.

SM22 is required for the maintenance of actin-rich structures generated during bacterial infections.

The host actin cytoskeleton is utilized by an assortment of pathogenic bacteria to colonize and cause disease in their hosts. Two prominently studied actin-hijacking bacteria are enteropathogenic Escherichia coli (EPEC) and Listeria monocytogenes. EPEC form actin-rich pedestals atop its host cells to move across the intestinal epithelia, while Listeria monocytogenes generate branched actin networks arranged as actin clouds around the bacteria and as comet tails for propulsion within and amongst their host cells.

Listeria Membrane Protrusion Collapse: Requirement of Cyclophilin A for Listeria Cell-to-Cell Spreading.

Background: Listeria generate actin-rich tubular protrusions at the plasma membrane that propel the bacteria into neighboring cells. The precise molecular mechanisms governing the formation of these protrusions remain poorly defined.

Methods: In this study, we demonstrate that the prolyl cis-trans isomerase (PPIase) cyclophilin A (CypA) is hijacked by Listeria at membrane protrusions used for cell-to-cell spreading.

Palladin Compensates for the Arp2/3 Complex and Supports Actin Structures during Infections.

Palladin is an important component of motile actin-rich structures and nucleates branched actin filament arrays Here we examine the role of palladin during infections in order to tease out novel functions of palladin. We show that palladin is co-opted by during its cellular entry and intracellular motility. Depletion of palladin resulted in shorter and misshapen comet tails, and when actin- or VASP-binding mutants of palladin were overexpressed in cells, comet tails disintegrated or became thinner.

Structure of the conserved Francisella virulence protein FvfA.

Francisella tularensis is a potent human pathogen that invades and survives in macrophage and epithelial cells. Two identical proteins, FTT_0924 from F. tularensis subsp.

Quantitative Mass Spectrometry Identifies Novel Host Binding Partners for Pathogenic Escherichia coli Type III Secretion System Effectors.

Enteropathogenic and enterohemorrhagic Escherichia coli cause enteric diseases resulting in significant morbidity and mortality worldwide. These pathogens remain extracellular and translocate a set of type III secreted effector proteins into host cells to promote bacterial virulence. Effectors manipulate host cell pathways to facilitate infection by interacting with a variety of host targets, yet the binding partners and mechanism of action of many effectors remain elusive.

Morphological analysis of Francisella novicida epithelial cell infections in the absence of functional FipA.

Francisella novicida is a surrogate pathogen commonly used to study infections by the potential bioterrorism agent, Francisella tularensis. One of the primary sites of Francisella infections is the liver where >90% of infected cells are hepatocytes. It is known that once Francisella enter cells it occupies a membrane-bound compartment, the Francisella-containing vacuole (FCV), from which it rapidly escapes to replicate in the cytosol.