Chemistry of Lipid A: At the Heart of Innate Immunity

Molinaro, Antonio; Holst, Otto; Lorenzo, Flaviana Di; Callaghan, Máire; Nurisso, Alessandra; D’Errico, Gerardino; Zamyatina, Alla; Peri, Francesco; Berisio, Rita; Jerala, Roman; Jiménez‐Barbero, Jesús; Silipo, Alba; Martín‐Santamaría, Sonsoles

doi:10.1002/chem.201403923

Cited by 205 publications

(189 citation statements)

References 204 publications

(470 reference statements)

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“…The inner leaflet of the OM comprises glycerophospholipids, and the external leaflet mainly comprises lipopolysaccharides (LPSs), which can cover up to 75% of the cell exterior 133,134 . LPS structures are highly strain-specific, but they can be roughly divided into three domains: a core oligosaccharide and a O-specific polysaccharide (or O-chain) that together form a hydrophilic heteropolysaccharide, and a lipophilic, membrane-anchoring domain, termed lipid A 135 . The hopanoids shown in the figure are present in some, but not all, Gram-negative and Gram-positive bacteria.…”

Section: Figure 1 |mentioning

confidence: 99%

Hopanoid lipids: from membranes to plant–bacteria interactions

et al. 2018

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Lipid research represents a frontier for microbiology, as showcased by hopanoid lipids. Hopanoids, which resemble sterols and are found in the membranes of diverse bacteria, have left an extensive molecular fossil record. They were first discovered by petroleum geologists. Today, hopanoid-producing bacteria remain abundant in various ecosystems, such as the rhizosphere. Recently, great progress has been made in our understanding of hopanoid biosynthesis, facilitated in part by technical advances in lipid identification and quantification. A variety of genetically tractable, hopanoid-producing bacteria have been cultured, and tools to manipulate hopanoid biosynthesis and detect hopanoids are improving. However, we still have much to learn regarding how hopanoid production is regulated, how hopanoids act biophysically and biochemically, and how their production affects bacterial interactions with other organisms, such as plants. The study of hopanoids thus offers rich opportunities for discovery.

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Section: Figure 1 |mentioning

confidence: 99%

Hopanoid lipids: from membranes to plant–bacteria interactions

et al. 2018

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“…1 A), previously also referred to as endotoxin. LPS can cover up to 75% of the surface [121], and its lipid A compound is seen as an endotoxin. The bacteria release small amounts of LPS as part of their normal metabolism and life cycle in outer membrane vesicles (OMV).…”

Section: Virulence Factorsmentioning

confidence: 99%

Aquaporins in Infection and Inflammation

Holm¹

2016

Linköping University Medical Dissertations

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About the cover:The front cover displays a human, blood-derived macrophage stained for aquaporin 9.During the course of the research underlying this thesis, Angelika Holm was enrolled in Forum Scientium, a multidisciplinary doctoral programme at Linköping University Printed by LiU-Tryck, Linköping, Sweden, 2016 "Be brave, even if you're not, pretend to be. No one can tell the difference."To that young, awkward, tall girl who dared to dream of something else, something more:You did it. SUPERVISOR Elena VikströmDepartment of Clinical and Experimental Medicine Linköping University Linköping Sweden When cells of the innate immune system encounter pathogens they need to respond and prepare for migration and phagocytosis and do so through volume regulatory processes. The Gramnegative bacterium Pseudomonas aeruginosa utilizes a small molecule-based communication system, called quorum sensing (QS) to control the production of its virulence factors and biofilms. We found that P. aeruginosa with a complete QS system elicits a stronger phagocytic response in human blood-derived macrophages compared to its lasI-/rhlI-mutant lacking the production of the QS molecules N-butyryl-L-homoserine lactone (C4-HSL) and N-3-oxododecanoyl-L-homoserine lactone (3O-C12-HSL). Infection with P. aeruginosa further increases the expression of AQP9 and induces re-localisation of AQP9 to the front and trailing ends of macrophages. Moreover, the 3O-C12-HSL alone elevates the expression of AQP9, redistribute the water channel to the front and rear ends and increases the cell area and volume of macrophages. Both infection with the wild type P. aeruginosa and the treatment with 3O-C12-HSL change the nano-structural architecture of the AQP9 distribution in macrophages. ASSISTANT SUPERVISORS Karl-Eric MagnussonViruses use the intracellular machinery of the invaded cells to produce and assemble new viral bodies. Intracellular AQPs are localised in a membranes of cellular organelles to regulate their function and morphology. C3H10T1/2 fibroblasts transiently expressing green fluorescent protein (GFP)-AQP6 show a reduced expression of AQP6 after Hazara virus infection and an increased cell area. Overexpressing AQP6 in C3H10T1/2 cells reduces the infectivity of Hazara virus indicating that AQP6 expression has a protective role in virus infections.Ion and water channels in the epithelial cell lining tightly regulate the water homeostasis. In microscopic colitis (MC), patients suffer from severe watery diarrhoeas. For the first time, we have shown that the expression of AQP1, 8 and 11 and the sodium/hydrogen exchanger NHE1 are reduced in colonic biopsies from MC patients compared to healthy control individuals. Following treatment with the glucocorticoid budesonide the patients experienced a rapid recovery and we observed a restored or increased expression of the AQPs and NHE1 during treatment, suggesting a role for AQPs in the diarrhoeal mechanisms in MC.Taken together, this thesis provides new evidence on the importance of water homeostasis regulatio...

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“…5 Existen diferencias en la estructura del lípido A entre las especies de bacterias, incluso, en la misma especie puede existir más de un una estructura química de lípido A. 6 Por ejemplo, el lípido A que frecuentemente tiene acilaciones de ácidos grasos con 12 o 14 carbonos puede variar dependiendo de la especificidad de las enzimas que realizan la acilación de los residuos de azúcares como es el caso de Bacteroides fragilis y Bordetella pertussis, en donde las enzimas que catalizan la acilación de los restos de azúcar parecen ser multifuncionales, por lo tanto, ser capaz de reconocer más de una cadena de acilo específica como sustrato. 7 Otras diferencias con respecto al lípido A de Escherichia coli que se presentan en otros géneros bacterianos consiste en el número de acilos presentes en el lípido A, como es el caso de Helicobacter pylori que tiene un lípido A tetracilado, diversas especies de Acinetobacter que presentan un lípido A heptacilado, o Pseudomonas con uno pentacilado.…”

Section: Estructura Del Lipopolisacáridounclassified

Modulación de la respuesta inmune por los lipopolisacáridos bacterianos

Aldapa-Vega

Pastelín-Palacios

Isibasí

et al. 2016

RAM

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Lipopolysaccharide (LPS) is a molecule that is profusely found on the outer membrane of Gramnegative bacteria and is also a potent stimulator of the immune response. As the main molecule on the bacterial surface, is also the most biologically active. The immune response of the host is activated by the recognition of LPS through Toll-like receptor 4 (TLR4) and this receptor-ligand interaction is closely linked to LPS structure. Microorganisms have evolved systems to control the expression and structure of LPS, producing structural variants that are used for modulating the host immune responses during infection. Examples of this include Helicobacter pylori, Francisella tularensis, Chlamydia trachomatis and Salmonella spp. High concentrations of LPS can cause fever, increased heart rate and lead to septic shock and death. However, at relatively low concentrations some LPS are highly active immunomodulators, which can induce non-specific resistance to invading microorganisms. The elucidation of the molecular and cellular mechanisms involved in the recognition of LPS and its structural variants has been fundamental to understand inflammation and is currently a pivotal field of research to understand the innate immune response, inflammation, the complex host-pathogen relationship and has important implications for the rational development of new immunomodulators and adjuvants.

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Chemistry of Lipid A: At the Heart of Innate Immunity

Cited by 205 publications

References 204 publications

Hopanoid lipids: from membranes to plant–bacteria interactions

Hopanoid lipids: from membranes to plant–bacteria interactions

Aquaporins in Infection and Inflammation

Modulación de la respuesta inmune por los lipopolisacáridos bacterianos

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