Distribution and characterization of Shiga toxin converting temperate phages carried by Shigella flexneri in
Marta Fogolari1, Carla Mavian2, Silvia Angeletti3
1Unit of Clinical Laboratory Science, University Campus Bio-Medico of Rome, Rome, Italy; Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA.
Abstract:
Shigella infections account for a considerable burden of acute diarrheal diseases worldwide and remain a major cause of childhood mortality in developing countries. Although, all four species of Shigella (S. dysenteriae, S. flexneri, S. boydii, and S. sonnei) cause bacillary dysentery, historically only S. dysenteriae type 1 has been recognized as carrying the genes for Shiga toxin (stx). Recent epidemiological data, however, have suggested that the emergence of stx carrying S. flexneri strains may have originated from bacteriophage-mediated inter-species horizontal gene transfer in one specific geographical area, Hispaniola. To test this hypothesis, we analyzed whole genome sequences of stx-encoding phages carried by S. flexneri strains isolated in Haiti and S. flexneri S. boydii and S. dysenteriae strains isolated from international travelers who likely acquired the infection in Haiti or the Dominican Republic. Phylogenetic analysis showed that phage sequences encoded in the Shigella strains from Hispaniola were bacteriophage φPOC-J13 and they were all closely related to a phage isolated from a USA isolate, E. coli 2009C-3133 serotype O119:H4. In addition, despite the low genetic heterogeneity of phages from different Shigella spp. circulating in the Caribbean island between 2001 and 2014, two distinct clusters emerged in Haiti and the Dominican Republic. Each cluster possibly originated from phages isolated from S. flexneri 2a, and within each cluster several instances of horizontal phage transfer from S. flexneri 2a to other species were detected. The implications of the emergence of stx-producing non-S. dysenteriae type 1 Shigella species, such as S. flexneri, spans not only the basic science behind horizontal phage spread, but also extends to medical treatment of patients infected with this pathogen.
Insights
Shiga toxin (stx)-producing Shigella flexneri strains emerged in Hispaniola due to bacteriophage gene transfer. This finding impacts understanding of diarrheal disease and treatment strategies.
Area of Science:
- Microbiology
- Genetics
- Epidemiology
Background:
- Shigella infections cause significant diarrheal disease and childhood mortality globally.
- Historically, only Shigella dysenteriae type 1 carried Shiga toxin (stx) genes.
- Emergence of stx-carrying S. flexneri suggests horizontal gene transfer via bacteriophages.
Purpose of the Study:
- To investigate the origin and spread of stx-encoding phages in Shigella strains from Hispaniola.
- To determine if bacteriophage-mediated horizontal gene transfer explains stx acquisition by non-S. dysenteriae type 1 Shigella species.
Main Methods:
- Whole genome sequencing of stx-encoding phages from Shigella strains isolated in Haiti and from international travelers.
- Phylogenetic analysis of phage sequences.
- Comparative analysis with known bacteriophages and E. coli isolates.
Main Results:
- Phages from Hispaniola Shigella strains were identified as bacteriophage φPOC-J13, closely related to a phage from a US E. coli isolate.
- Two distinct phage clusters were identified in Haiti and the Dominican Republic, originating from S. flexneri 2a.
- Evidence of horizontal phage transfer from S. flexneri 2a to other Shigella species was detected.
Conclusions:
- Bacteriophage-mediated horizontal gene transfer is a mechanism for the emergence of stx-producing Shigella flexneri in Hispaniola.
- The findings have implications for understanding diarrheal disease pathogenesis and developing effective medical treatments.
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