Shigella Diversity and Changing Landscape: Insights for the Twenty-First Century

Abstract

Shigella is a pathovar of Escherichia coli comprising four groups, Shigella flexneri, Shigella sonnei, Shigella dysenteriae, and Shigella boydii, each of them, with the exception of S.sonnei, comprising several serotypes. Shigella accounts for the majority of dysentery causing infections occurring world-wide each year. Recent advancements in the Shigella field have led to a better understanding of the molecular mechanisms underlying host epithelial cell invasion and immune cell function manipulation, mainly using S. flexneri as a model. Host-cell invasion is the final step of the infection process, as Shigella's virulence strategy relies also on its ability to survive hostile conditions during its journey through the gastro-intestinal tract, to compete with the host microbiota and to cross the intestinal mucus layer. Hence, the diversity of the virulence strategies among the different Shigella species has not yet been deeply investigated, which might be an important step to understand the epidemiological spreading of Shigella species worldwide and a key aspect for the validation of novel vaccine candidates. The recent development of high-throughput screening and sequencing methods will facilitate these complex comparison studies. In this review we discuss several of the major avenues that the Shigella research field has taken over the past few years and hopefully gain some insights into the questions that remain surrounding this important human pathogen.

Keywords: Shigella; diversity; microbiota; mucus; virulence.

Figure 1

Comparison of selected Shigella O-antigen side chains. Schematic of repeated O-antigen side chains from serotypes S. sonnei (Gamian and Romanowska, 1982), S. flexneri 5a (Perepelov et al., 2010), S. dysenteriae 1 (Dmitriev et al., 1976), and S. boydii 6 (Senchenkova et al., 2005). Figure legend abreviations are as follows 2-Acetamido-2-deoxy-D-glucose (D-GlcNAc), 2-Acetamido-2-deoxy-L-altruronic acid (L-AltNAc), 2-Acetamido-4-amino-2, 4-dideoxy-D-fucose (D-FucNAc), 2-Acetamido-2-deoxy-D-galacturonic acid (D-GalNAc), D-Galactopyranose (D-Gal), D-Mannose (D-Man), L-Rhamnose (L-Rha), D-Glucose (D-Glc), O-acetyl (Ac).

Figure 2

Prevelance of Shigella species across China 2003–2013. Comparison of reported Shigella species between 2003–2004 and 2011–2013 showing the increase in S. sonnei isolations. For years 2003–2004 n = 235 cases, for 2011–2013 n = 1049 cases. Prevelance data reported in Qiu et al. (2015).

Figure 3

During Shigella infection, the colonic microbiota and mucus layers stand as the first barriers protecting the epithelium lineage. (A) The microbiota colonizes the colonic lumenal compartment, and the outer mucus layer. The inner mucus sterile remains sterile probaly due to its mechanical properties and accumulation of secreted antimicrobial peptides (AMPs). (B) Shigella secrete proteins belonging to the SPATE family, including Pic characterized in S. flexneri 2a (Henderson et al., ; Gutiérrez-Jiménez et al., ; Navarro-Garcia et al., ; Ruiz-Perez et al., 2011) and SepA identified in S. flexneri 5a (Benjelloun-Touimi et al., 1995). Shigella SPATE proteins cleave mucins to allow the bacteria to reach the epithelial layer. Shigella Type III secretion apparatus (T3SA) is required for epithelium invasion.