Intracellular spread protein IcsA (IcsA)

Intracellular spread protein IcsA, also known as VirG, is a 120 kDa outer membrane autotransporter protein primarily found in Shigella species, such as Shigella flexneri [1, 2]. It plays a pivotal role in bacterial pathogenesis by mediating actin-based motility, which allows the pathogen to move within the host cell cytoplasm and spread to adjacent cells [3, 5]. IcsA achieves this by polarly localizing on the bacterial surface and recruiting host cell factors, specifically neural Wiskott-Aldrich syndrome protein (N-WASP) and the Arp2/3 complex, to trigger actin polymerization [3, 12]. This process forms actin comet tails that propel the bacteria, facilitating the formation of protrusions and subsequent infection of neighboring cells [8, 13]. Additionally, IcsA functions as an adhesin and is involved in biofilm formation and the evasion of host autophagy by interacting with proteins like IcsB and Atg5 [1, 4, 7]. Because it is essential for virulence and conserved across various serotypes, IcsA is a major target for the development of vaccines, such as multiepitope fusion antigens (MEFA), and anti-virulence therapies aimed at disrupting bacterial dissemination [4, 11]. Experimental inhibitors like A22 and MP265 have been shown to disrupt its polar localization, highlighting its potential as a therapeutic target [6, 9].

Other names

VirGVirulence gene G proteinAutotransporter protein IcsAIcsA autotransporter

Inhibition of polar localization, blocking of N-WASP recruitment, or induction of neutralizing antibodies to prevent bacterial adhesion and spread.