Actin machinery of phagocytic cells: Universal target for bacterial attack

Abstract

Uptake of microorganisms by eukaryotic cells depends on proper functioning of the actin machinery. It creates a driving force for the cell membrane deformations necessary for ingestion and killing of microbes by phagocytes. Therefore, specific alterations in the activity of the actin apparatus could be favorable for pathogenic bacteria, representing an efficient mechanism in their virulence. Such alterations are supposed to be achieved in two principle ways. One is accomplished via binding of bacterial ligands to certain surface receptors, which initiate subsequent actin cytoskeleton rearrangements. Another is to introduce cytoskeleton-targeted products directly into eukaryotic cells and in this way modulate the activity of the actin apparatus. Indeed, Legionella and some other intracellular parasites possess ligands able to stimulate certain receptors on the surface of phagocytes and possess devices suitable for translocation of effector molecules into eukaryotic cytoplasm. The results of such events could be increased uptake of these microbes and their subsequent transportation to permit multiplication in their intracellular niche. On the contrary, representatives of Clostridium and a number of other extracellular pathogens create products which penetrate eukaryotic cells and disorganize the actin cytoskeleton network, thus making uptake of these pathogens by phagocytes impossible.

Legionella pneumophila carrying the virulence-associated lipopolysaccharide epitope possesses two functionally different LPS components

“…The target of shed Legionella LPS components has remained speculative up to now; however, the cytoskeleton is the most likely target, as has been substantiated for many Gram-negative bacteria (Belyi, 2002). Interestingly, mAb 3/1positive LPS shed in the non-vesicular fraction from the E phase does not contain very long O-specific chains (Fig.…”

Purification and Characterization of a UDP-Glucosyltransferase Produced by Legionella pneumophila

“…The diseases caused by these clostridia have different clinical and epidemiological manifestations; C. difficile is an agent of antibiotic-associated diarrhea and pseudomembranous colitis in humans, C. sordellii produces gas gangrene, diarrhea, and enterotoxemia in humans and animals, and C. novyi causes gas gangrene in humans and animals (21,31). However, a common feature of these diseases is that they all involve bacterial extracellular proliferation in the face of an inflammatory response (7). It has been speculated that inhibition of phagocytosis may result from the toxins' ability to target Ras-related proteins, which are important regulators of actin cytoskeleton rearrangements (1,20,32,47).…”

Macrophage induced gelsolin in response to Group BStreptococcus(GBS) infection

“…In fact, Ca 2+ signalling has been implicated in a wide range of bacterial infection processes, among which the respiratory burst, the control of gene expression – especially that leading to the expression and secretion of proinflammatory mediators – cytoskeletal reorganization and degradation, and induction of apoptosis (May and Machesky, ; TranVan Nhieu et al ., ; Groves et al ., ; Melendez and Tay, ). Ca 2+ plays many different roles in these processes by affecting the actions of intracellular Ca 2+ ‐sensing proteins, among which gelsolin, which in particular plays a crucial role in cytoskeletal modulation and apoptosis (May and Machesky, ; Belyi, ; Groves et al ., ; Melendez and Tay, ; Li et al ., ). Gelsolin is a Ca 2+ ‐dependent and PI(4,5)P2‐regulated cytoskeleton protein composed of six repeating domains of sequence (G1–6).…”