Journal Article

Manipulation of host membranes by bacterial effectors

Orth, Kim, Ham, Hyeilin, Sreelatha, Anju

2011

Overview

Key Points On infection, bacterial pathogens interact with host membranes to trigger various cellular processes through different mechanisms. These processes include alterations to the dynamics between the plasma membrane and the actin cytoskeleton, and subversion of the membrane-associated pathways that are involved in vesicle trafficking. Many bacterial effectors manipulate phosphoinositide (PI) homeostasis at the plasma membrane to destabilize actin dynamics and alter the morphology of the membrane. This facilitates the entry of pathogens or, in other cases, damages the cells by disrupting membrane integrity and eventually leading to rapid cell lysis in the later stage of infection. Some pathogens use bacterial phosphatases or PI adaptor proteins to form intracellular vacuoles that are derived from host membranes in order to establish a replicative niche. Altered PI levels at the surfaces of these vacuoles as a result of the activity of bacterial phosphatases can block phagosomal maturation to avoid lysosomal fusion. The GTPase signalling pathway is often targeted by bacterial pathogens to manipulate the actin cytoskeleton and endosomal trafficking. RAB GTPases , which have an important role in vesicular trafficking pathways, are recruited to bacterium-containing vacuoles, where their active state can be differentially regulated by effectors. Bacterial effectors mimic GTPase-activating protein (GAP) or guanine nucleotide exchange factor (GEF) activity to target RHO-family GTPases that are key regulators of actin dynamics. This results in loss of cell shape, motility and ability to phagocytose pathogens. Autophagy is one of the cellular defence mechanisms against the invasion of pathogenic bacteria. However, some pathogens have evolved strategies to subvert autophagy to their own advantage by establishing autophagic vesicles as their replicative niche. This allows them to survive inside host cells and avoid lysosomal degradation. Some bacterial effectors are speculated to induce autophagy during infection. This may not only protect the bacteria from degradative enzymes and immune responses, but also provide nutrients from cellular debris. For extracellular pathogens, inducing autophagy helps prevent phagocytosis. Bacterial pathogens secrete a range of effector proteins to target the signalling pathways that regulate host cell membranes. Here, Orth and colleagues describe the bacterial effectors that target phosphoinositide signalling, GTPase signalling and autophagy, and discuss how targeting these pathways can alter host membrane dynamics. Bacterial pathogens interact with host membranes to trigger a wide range of cellular processes during the course of infection. These processes include alterations to the dynamics between the plasma membrane and the actin cytoskeleton, and subversion of the membrane-associated pathways involved in vesicle trafficking. Such changes facilitate the entry and replication of the pathogen, and prevent its phagocytosis and degradation. In this Review, we describe the manipulation of host membranes by numerous bacterial effectors that target phosphoinositide metabolism, GTPase signalling and autophagy.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/326/41/2531 / 631/326/41/2534 / 692/699/255/1318 / 88 / Actin / Autophagy / Bacteria / Bacteria - pathogenicity / Bacterial Infections - microbiology / Biomedical and Life Sciences / Cell Membrane - metabolism / Cell Membrane - microbiology / Cytoskeleton / Endoplasmic reticulum / Health aspects / Host-Pathogen Interactions / Humans / Infections / Infectious Diseases / Life Sciences / Medical Microbiology / Membranes / Membranes (Biology) / Metabolism / Microbiology / Muscle proteins / Parasitology / Pathogens / Phosphatidylinositols - metabolism / Physiological aspects / Plasma / Proteins / review-article / Salmonella / Signal Transduction / Virology / Virulence