The Rising Dominance of Shigella sonnei: An Intercontinental Shift in the Etiology of Bacillary Dysentery

Abstract

Shigellosis is the major global cause of dysentery. Shigella sonnei, which has historically been more commonly isolated in developed countries, is undergoing an unprecedented expansion across industrializing regions in Asia, Latin America, and the Middle East. The precise reasons underpinning the epidemiological distribution of the various Shigella species and this global surge in S. sonnei are unclear but may be due to three major environmental pressures. First, natural passive immunization with the bacterium Plesiomonas shigelloides is hypothesized to protect populations with poor water supplies against S. sonnei. Improving the quality of drinking water supplies would, therefore, result in a reduction in P. shigelloides exposure and a subsequent reduction in environmental immunization against S. sonnei. Secondly, the ubiquitous amoeba species Acanthamoeba castellanii has been shown to phagocytize S. sonnei efficiently and symbiotically, thus allowing the bacteria access to a protected niche in which to withstand chlorination and other harsh environmental conditions in temperate countries. Finally, S. sonnei has emerged from Europe and begun to spread globally only relatively recently. A strong selective pressure from localized antimicrobial use additionally appears to have had a dramatic impact on the evolution of the S. sonnei population. We hypothesize that S. sonnei, which exhibits an exceptional ability to acquire antimicrobial resistance genes from commensal and pathogenic bacteria, has a competitive advantage over S. flexneri, particularly in areas with poorly regulated antimicrobial use. Continuing improvement in the quality of global drinking water supplies alongside the rapid development of antimicrobial resistance predicts the burden and international distribution of S. sonnei will only continue to grow. An effective vaccine against S. sonnei is overdue and may become one of our only weapons against this increasingly dominant and problematic gastrointestinal pathogen.

Fig 1. The ratio of S. sonnei to S. flexneri isolated from 100 countries, 1990–2014.

The darker the color, the higher the proportion of S. sonnei isolated from each country; the lighter the color, proportionally higher the proportion of S. flexneri isolated. Countries colored grey indicate no data on species were identified. To generate this map, we performed an extensive literature review in PubMed using the term “Shigella” followed by the name of 178 countries. The most recent publication that included species information that was nonoutbreak and nontravel associated was included as representative of each country. If country data were pre-1990 or were not available on PubMed, the Gideon Infectious Disease encyclopedia as well as national reference laboratory data were referenced where possible. References are listed by country in the supplementary material (S1 Table).

Fig 2. Antimicrobial resistance and presence of resistance-conferring genes in S. sonnei and S. flexneri.

Plots on the left show proportion of antimicrobial resistance determined by minimum inhibitory concentration (MIC) amongst isolates collected from Vietnam over a 15-year period (n = 231 for S. sonnei and 136 for S. flexneri) [34,56]. S. sonnei are shown by darker colors on the top of each graph, and S. flexneri is shown by lighter colors at the bottom. Plots on the right show the proportion of S. sonnei (dark color, top of each graph) and S. flexneri (light color, bottom of each graph) found to have varying resistance genes present on either plasmids or the chromosome. See Supporting Information (SI) S1 Text for a description of procedures. The color of the gene corresponds with the color of the antimicrobial to which it confers resistance on the left. AMP: ampicillin; CHL: chloramphenicol; CIP: ciprofloxacin; CRO: ceftriaxone; GAT: gatifloxacin; GEN: gentamicin; NAL: nalidixic acid; OFX: ofloxacin; SXT: cotrimoxazole; TET: tetracycline; TMP: trimethoprim.