Submitted by Narine Arabyan
Salmonella enterica spp. enterica sv Typhimurium is one of the most important foodborne pathogens causing gastroenteritis in humans1. WHO (2005) with USDA and CDC estimated that Salmonella infections account for 1.4 -1.6 million cases per year of foodborne illnesses in USA and approach 1.5 billion cases worldwide2. Salmonella infections result in about 5000 deaths making it one of the most common enteric pathogens3. The economic impact of Salmonella infections on human health in the United States is estimated to cost up to $2.3 billion dollars per year. The occurrence of this bacterium continues to persist in causing disease in humans, largely via the food supply, indicating that additional effort is needed to define new interventions. This combined with emergence of hypervirulent isolates suggest that the genetic diversity is effectively circumventing the control strategies for this organism2. Increased surveillance, current approaches of biocontrol, additional hygiene intervention, and animal vaccinations are not effective in controlling Salmonella in the food supply. As an invasive pathogen, Salmonella needs to gain access to the host cell membrane before entering the intestinal cell. Epithelial cells in the gastrointestinal tract are covered with multiple layers of complex oligosaccharides (mucin and glycocalyx) that protect the cell from the local environment and infection4. The glycocalyx layer, composed of diverse glycans, is a complex barrier that is a component of lipid rafts, and are attached to transmembrane glycoproteins and glycolipids used by bacteria as receptors, to mediate infection5,6. Use of the glycan by viruses, such as avian influenza is well recognized, especially via sialic acid7-9. Recently, our group discovered that Salmonella degrades the cellular glycan via sialic acid during infection opening many new questions about what specific glycosyl hydrolases (GHs) are used to degrade the glycans to invade the host cell10. Specific genes in the microbe are needed to degrade the glycan during infection. These genes are poorly characterized and ill-defined. We defined that Salmonella Typhimurium contains 48 annotated genes for GHs that may degrade the glycan and promote infection. Weimer’s group (Arabyan et al. 2016) demonstrated that Salmonella degrades the glycan using GH enzymes to reach the membrane and change infection10. This innovative approach along with innovative set of genes has opened a novel avenue in defining glycan degrading genes as new targets for controlling infection and persistence in Salmonella and other enteric pathogens.
This recently published paper can be found at http://www.nature.com/articles/srep29525.
- Thiennimitr, P., Winter, S. E. & Baumler, A. J. Salmonella, the host and its microbiota. Current opinion in microbiology 15, 108-114, doi:10.1016/j.mib.2011.10.002 (2012).
- Heithoff, D. M. et al. Intraspecies variation in the emergence of hyperinfectious bacterial strains in nature. PLoS pathogens 8, e1002647, doi:10.1371/journal.ppat.1002647 (2012).
- Scallan, E. et al. Foodborne illness acquired in the United States–major pathogens. Emerging infectious diseases 17, 7-15, doi:10.3201/eid1701.091101p1 (2011).
- Moran, A. P., Gupta, A. & Joshi, L. Sweet-talk: role of host glycosylation in bacterial pathogenesis of the gastrointestinal tract. Gut 60, 1412-1425, doi:10.1136/gut.2010.212704 (2011).
- McGuckin, M. A., Linden, S. K., Sutton, P. & Florin, T. H. Mucin dynamics and enteric pathogens. Nature reviews. Microbiology 9, 265-278, doi:10.1038/nrmicro2538 (2011).
- Varki, A. Evolutionary forces shaping the Golgi glycosylation machinery: why cell surface glycans are universal to living cells. Cold Spring Harbor perspectives in biology 3, doi:10.1101/cshperspect.a005462 (2011).
- Walther, T. et al. Glycomic analysis of human respiratory tract tissues and correlation with influenza virus infection. PLoS pathogens 9, e1003223, doi:10.1371/journal.ppat.1003223 (2013).
- Chan, R. W. et al. Infection of swine ex vivo tissues with avian viruses including H7N9 and correlation with glycomic analysis. Influenza and other respiratory viruses 7, 1269-1282, doi:10.1111/irv.12144 (2013).
- de Graaf, M. & Fouchier, R. A. Role of receptor binding specificity in influenza A virus transmission and pathogenesis. The EMBO journal 33, 823-841, doi:10.1002/embj.201387442 (2014).
- Arabyan, N. et al. Salmonella Degrades the Host Glycocalyx Leading to Altered Infection and Glycan Remodeling. Sci Rep 6, 29525, doi:10.1038/srep29525 (2016).