Acting on Actin During Bacterial Infection

Abstract

Bacterial resistance to antibiotics is becoming a major threat to public health. It is imperative to find new therapeutic interventions to fight pathogens. Thus, deciphering host-pathogen interactions may allow defining targets for new strategies for effective treatments of infectious diseases. This chapter focuses on the bacterial manipulation of the host cell actin cytoskeleton. We discuss three infectious processes. The first is pathogen establishment of infection/invasion, explaining cellular uptake pathways that rely on actin, such as phagocytosis and macropinocytosis. The second process focus on the establishment of a replication niche, a process that subverts cytoskeletal functions associated with membrane trafficking namely phagosome maturation and cellular innate immune responses. Finally, pathogen dissemination is an emerging field that microfilaments have shown to participate: pathogen motility through the cytoplasm and from cell-to-cell or on the outer surface of the plasma membrane mimicking a receptor tyrosine kinase signaling pathway that helps the projection of pathogens to neighboring cells. It also establishes a connection with the innate immunity related with induction of cell signaling to inflammation, inflammasome activation, and programmed cell death. These studies revealed several potential targets related to actin cytoskeleton manipulation to design new therapeutic strategies for bacterial infections.

Wnt5A-Mediated Actin Organization Regulates Host Response to Bacterial Pathogens and Non-Pathogens

“…The intrinsic association of cytoskeletal actin with bacterial infections ( 19 , 40 ) led us to investigate if killing vs. survival of the pathogenic and non-pathogenic E. coli by Wnt5A signaling is associated with actin assembly.…”

“…Host-pathogen interactions focusing on how various bacterial pathogen specific virulence factors hijack the actin cytoskeleton have been extensively described ( 19 , 25 ). But how the host defense system incorporates the actin network to counter bacterial infections remains unclear.…”

“…Macrophages are intrinsically wired to counter bacterial infections through phagocytosis, which utilizes the coordination of the actin cytoskeleton with different signals ( 17 – 19 ). While some pathogenic bacteria fall prey to macrophages, others escape the immune defense program therein through either self-extrusion or creation of a protective intracellular niche ( 20 , 21 ).…”

The Interplay of Host Lysosomes and Intracellular Pathogens

“…One common strategy employed by many pathogens is to avoid trafficking to lysosomes (Meŕesse et al, 1999b;Duclos and Desjardins, 2000;Alix et al, 2011;Tang, 2015;Martinez et al, 2018). Several pathogens secrete effectors that target key host factors such as Rab GTPases (Deretic et al, 1997;Via et al, 1997;Fratti et al, 2001;Vergne et al, 2003b;Smith et al, 2007;Seto et al, 2011;Sherwood and Roy, 2013;Pradhan et al, 2018), cytoskeleton and motor protein (Dramsi and Cossart, 1998;Bearer and Satpute-Krishnan, 2002;Rottner et al, 2005;Henry et al, 2006b;Haglund and Welch, 2011;Shimono et al, 2016;Anes, 2017;Zhou et al, 2018) and block the fusion with lysosomes (Via et al, 1997;Russell, 2001;Pieters, 2008;Pradhan et al, 2018), instead residing in a modified phagosome, often called the pathogen containing vacuole (PCV) (Haas, 2007).…”

Host Response to Bacterial Pathogens and Non-Pathogens is Determined by Wnt5A Mediated Actin Organization

“…Macrophages are intrinsically wired to use lamellipodia and filopodia to counter and control bacterial infections through phagocytosis, which utilizes the coordination of the actin cytoskeleton with different environmental signals (18)(19)(20). While some internalized pathogenic bacteria fall prey to macrophages getting killed, others escape the immune defense program through either self-extrusion or creation of a protective intracellular niche (21,22).…”