Name: lipopolysaccharides and gram-negative defense
Uploaded: 2025-06-12T09:39:09.000Z
Duration: 1 min 19 s
Channel: JoVE

Los lipopolisacáridos o LPS son esenciales para las bacterias Gram-negativas, ya que proporcionan soporte estructural y ayudan a la evasión inmunitaria. El LPS está formado por el lípido A, un oligosacárido central, y el antígeno O. La biosíntesis de lípidos A comienza en el citoplasma con la uridina difosfato N-acetilglucosamina, que sufre acilación enzimática. Forma un intermediario tetra-acilado que sufre modificaciones secuenciales a medida que se agregan ácidos grasos adicionales. Una mayor acilación produce un lípido A hexa-acilado; a continuación, las glicosiltransferasas se unen secuencialmente al oligosacárido central al lípido A.Este complejo de núcleo lipídico A es transportado a través de la membrana interna por el transportador MsbA. Mientras tanto, el antígeno O se ensambla en un lípido portador en el citoplasma y se voltea al periplasma. En el periplasma, las unidades de antígeno O se polimerizan y se ligan al núcleo lipídico A, formando el LPS completo. Finalmente, el sistema de transporte de lipopolisacáridos mueve el LPS a través del periplasma y lo incorpora a la membrana externa, fortaleciendo las defensas bacterianas.

formación de lipopolisacáridos

Formation of Lipopolysaccharides

Los lipopolisac&#225;ridos (LPS) son componentes fundamentales de la membrana externa de las bacterias Gram-negativas, desempe&#241;ando funciones tanto estructurales como funcionales. Contribuyen a la estabilidad de la membrana y protegen a las bacterias frente a las respuestas inmunitarias del hospedador. El LPS est&#225; compuesto por tres regiones principales: l&#237;pido A, un oligosac&#225;rido central y un ant&#237;geno O. La bios&#237;ntesis y el ensamblaje del LPS implican un conjunto altamente coordinado de reacciones enzim&#225;ticas y mecanismos de transporte. Adem&#225;s, el LPS es reconocido como una endotoxina, capaz de desencadenar respuestas inmunitarias fuertes en el hospedador a trav&#233;s del receptor tipo Toll 4 (TLR4). Esta respuesta puede provocar inflamaci&#243;n y, en casos graves, shock s&#233;ptico.
Bios&#237;ntesis del l&#237;pido A
El l&#237;pido A, componente t&#243;xico del LPS, se sintetiza en el citoplasma a partir de uridina difosfato N-acetilglucosamina (UDP-GlcNAc). Mediante reacciones de acilaci&#243;n enzim&#225;tica se incorporan secuencialmente &#225;cidos grasos a la UDP-GlcNAc, dando lugar a un precursor de l&#237;pido A tetra-acilado. Este intermedio sufre modificaciones, incluyendo acilaciones sucesivas, hasta convertirse en l&#237;pido A maduro hexa-acilado. Algunas bacterias, como Salmonella y Yersinia, modifican a&#250;n m&#225;s el l&#237;pido A mediante la adici&#243;n de fosfoetanolamina o aminoarabinosa, lo que incrementa su resistencia frente a p&#233;ptidos antimicrobianos. El l&#237;pido A completamente ensamblado permanece anclado a la membrana interna a la espera de modificaciones adicionales.
Ensamblaje del oligosac&#225;rido central y del ant&#237;geno O
El oligosac&#225;rido central se une de forma secuencial al l&#237;pido A mediante glicosiltransferasas. Esta regi&#243;n central es esencial para la integridad de la membrana y sirve como plataforma para el ant&#237;geno O. El ant&#237;geno O, un polisac&#225;rido compuesto por unidades repetidas de az&#250;cares, se sintetiza por separado sobre el transportador lip&#237;dico fosfato de undecaprenilo. La longitud y composici&#243;n azucarada del ant&#237;geno O var&#237;an entre especies bacterianas, lo que influye en el reconocimiento inmunitario y en la virulencia.
Ensamblaje y transporte del LPS
Una vez que el l&#237;pido A est&#225; unido al oligosac&#225;rido central, la enzima flipasa MsbA transloca ambas estructuras a trav&#233;s de la membrana interna. De forma simult&#225;nea, el ant&#237;geno O polimerizado es transportado al periplasma. Una enzima ligasa une covalentemente el ant&#237;geno O al complejo l&#237;pido A&#8211;oligosac&#225;rido central, completando as&#237; la estructura del LPS.
El LPS maduro es transportado posteriormente a la membrana externa por el sistema Lpt (transporte de lipopolisac&#225;ridos), un complejo multiproteico que garantiza su localizaci&#243;n adecuada. Este proceso de transporte depende de ATP, siendo el complejo LptBFG en la membrana interna el que suministra la energ&#237;a necesaria. La correcta localizaci&#243;n del LPS refuerza la membrana externa, incrementando la resistencia bacteriana a los antibi&#243;ticos, a los factores inmunitarios del hospedador y factores de estr&#233;s ambiental.

Formación de lipopolisacáridos

Los lipopolisac&#225;ridos (LPS) son componentes fundamentales de la membrana externa de las bacterias Gram-negativas, desempe&#241;ando funciones tanto ...

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Microbial Metabolism

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lipopolysaccharides and gram-negative defense

Lipopolysaccharides (LPS) are important parts of the outer membrane of Gram-negative bacteria. They help stabilize the membrane and help protect bacteria from host immune responses. LPS has three main parts: lipid A, a core oligosaccharide, and an O antigen.

LPS biosynthesis and assembly depend on a coordinated set of enzymes and transport steps. The molecule is also known as an endotoxin. It can activate Toll-like receptor 4 (TLR4) in the host and trigger strong immune responses. In severe cases, this response can lead to inflammation and septic shock.

Lipid A is the toxic part of LPS. It is made in the cytoplasm, beginning with uridine diphosphate N-acetylglucosamine, or UDP-GlcNAc. Enzymes add fatty acids in a stepwise acylation process to form a tetra-acylated precursor. Further acylations produce mature hexa-acylated lipid A. Some bacteria, including Salmonella and Yersinia, add phosphoethanolamine or aminoarabinose to lipid A. These changes can increase resistance to antimicrobial peptides. The finished lipid A stays anchored in the inner membrane.

The core oligosaccharide is added next by glycosyltransferases. This core region helps maintain membrane integrity and acts as a scaffold for the O antigen. The O antigen is a repeating sugar chain made separately on the lipid carrier undecaprenyl phosphate. Its length and sugar makeup vary among bacterial species. These differences can affect immune recognition and virulence.

After lipid A is linked to the core oligosaccharide, the MsbA flippase moves both parts across the inner membrane. At the same time, the polymerized O antigen is flipped into the periplasm. A ligase then joins the O antigen to the lipid A-core complex to finish LPS assembly. The mature LPS is carried to the outer membrane by the Lpt transport system, which is a multiprotein complex. The inner-membrane LptBFG complex uses ATP for energy. Proper LPS placement strengthens the outer membrane and increases resistance to antibiotics, host immune factors, and environmental stressors.

Lipopolysaccharides and Gram-Negative Defense

lipopolysaccharides-and-gram-negative-defense

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key terms and concepts

Learn how lipopolysaccharides are built, moved, and attached in Gram-negative bacteria, and how LPS helps protect cells and trigger immune responses.

Lipopolysaccharides and Gram-Negative Defense | JoVE K12

JoVE Core Microbiology provides an engaging introduction to the microbial world and its influence on health, industry, and the environment. This comprehensive collection covers key concepts such as microbial structure, metabolism, genetics, and ecology. It introduces essential laboratory techniques and microscopy methods through visually engaging animations. Corresponding scientist-in-action videos bridge classroom concepts with real-world research and applications.

microbiology

Lipopolysaccharides and Gram-Negative Defense

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