1. Introduction

The eukaryotic cell cytoskeleton is a complex and dynamic network that shapes the cell and plays a key role in numerous cellular processes such as cell migration, adhesion, internalization and intracellular trafficking. To achieve all these dynamic events, the cell cytoskeleton involves several proteins, among which the subject of this Special Issue, the myosins.

Myosins constitute a superfamily of actin-based motor proteins that share properties of actin-binding, chemical-to-mechanical energy conversion (ATPase activity) and directed movement along actin filaments (generally to the plus-end filament)^[1]. All myosins are composed of three domains, namely the head, neck, and tail domains, forming the myosin heavy chain. Localized at the N-terminus, the globular head domain contains evolutionarily conserved actin- and ATP-binding sites with ATPase activity. This domain is thus dedicated to the motor function of myosins by generating force via the ATP hydrolysis and by converting chemical energy into mechanical work^[2]. The central neck domain, also known as the “lever-arm”, is an α-helical segment ^[3] that amplifies the movement originating from the motor domain. Following ATP hydrolysis, the lever-arm region rotates to amplify the angstrom-level conformational changes in the motor domain to the nanometer-sized power-stroke motions^[4]. It contains one or several IQ motifs whose function is to bind regulatory elements of motor function, such as calmodulin or myosin light chains (MLC)^[5]. Finally, the C-terminal tail domain, as the most variable region of the myosins, determines the specific cellular functions of the different myosin classes by presenting different binding sites to molecular cargos such as SRC Homology 3 (SH3), GTPase-activating protein (GAP), four-point-one, ezrin, radixin, moesin (FERM) or Pleckstrin homology (PH) domains^[6]. For some classes, such as myosins II and V, the tail region may also contain regions predicted to be coiled-coil domains when myosins molecules form dimers.

Human myosins, classified in around 18 families, participate in a diversity of cellular processes, including cell migration and adhesion, signal transduction, intracellular and membrane trafficking^[7]. In addition to these essential functions for the eukaryotic cell, it recently appeared that some myosins, from class I, II, VI, VII, IX and X, are also at the heart of the infectious cycle of many intracellular bacteria. Specifically, given the key role of myosins in eukaryotic cell biology, bacteria have evolved strategies that target and hijack the host cell myosins to their own benefit.

2. Myosins, an Underestimated Player in the Infectious Cycle of Pathogenic Bacteria

Myosins are a crucial and very conserved element of the cytoskeleton that plays a key role in the homeostasis and general biology of the eukaryotic cells, including cell migration and adhesion, signal transduction, intracellular and membrane trafficking, involved in particular in endocytosis, phagocytosis and vesicular trafficking. The role of myosins in essential cell processes makes them ideal targets for bacteria to hijack host cell pathways to their benefit and to evade immune defenses in order to efficiently infect, replicate and disseminate in their host. Thus, some extracellular bacteria, but even more intracellular bacteria have evolved sophisticated strategies that target myosins to go through different stages of their infectious cycle: (i) adhesion to the host cell, for EPEC^[8]; (ii) invasion, i.e., entry into non-phagocytic cells, for Salmonella^[9], Shigella^[10], and Listeria ^[11]; (iii) evasion from the cytosolic autonomous cell defenses among which autophagy, for Shigella and Listeria; (iv) biogenesis of a replicative niche, such as the vacuole of Salmonella^[12]; (v) dissemination in tissues by the cell-to-cell spreading for Shigella and Listeria^[13]; (vi) exit out of the host cell for Chlamydia^[14]; (vii) evasion from phagocytosis for EPEC. Noteworthy, bacteria can activate or inhibit the myosin-dependent processes, depending on the infection step involved. Importantly, various myosins are targeted by bacteria, but the prevalent involvement of myosin II in the host–bacteria relationship can be noted, possibly due to its key role in many mechanical tasks, including the regulation of adhesion and intracellular trafficking (endocytosis, exocytosis, phagocytose and vesicular transport). With the exception of the bacterial effector EspB from EPEC, which directly interacts with the C-terminal domain of myosin Ic, thus competing with actin for binding this myosin, most of the mechanisms involved in the manipulation of myosins are based on indirect interactions leading to post-translational modifications of myosins or triggering complex signaling pathways that activate or inhibit myosins.

Myosins are not the only cytoskeletal protein targeted by a wide variety of bacteria. Indeed, the actin cytoskeleton (-F, -G and polymerization) seems to be a privileged target for bacteria^[15], particularly with regard to bacterial entry or propagation between neighboring cells^[16]. Interestingly, the study of the interaction between bacteria^[17] and the host cell actin cytoskeleton has advanced not only our knowledge in bacteriology but also our understanding of the dynamic mechanisms governing the host cell cytoskeleton. Thus, basic research on Listeria infectious cycle, and in particular its entry into epithelial cells, its intracellular motility and its cell-to-cell dissemination has allowed the astonishing discovery of the first nucleation promoting factor (NPF), ActA, a Listeria protein surface that allowed the recruitment of cellular protein vasodilator-stimulated-phosphoprotein (VASP)^[18] and consequently actin polymerization at one pole of the bacteria. This breakthrough discovery has paved the way for the discovery of other NPFs and the understanding of molecular mechanisms that finely control the dynamics of actin polymerization. Similarly, it can be expected that the deepening of our knowledge of the host–pathogen interaction could lead to the discovery of new mechanisms associated with myosins.