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. 2013 Oct 10;7(10):e2487.
doi: 10.1371/journal.pntd.0002487. eCollection 2013.

Invasive non-typhoidal Salmonella typhimurium ST313 are not host-restricted and have an invasive phenotype in experimentally infected chickens

Affiliations

Invasive non-typhoidal Salmonella typhimurium ST313 are not host-restricted and have an invasive phenotype in experimentally infected chickens

Bryony N Parsons et al. PLoS Negl Trop Dis. .

Abstract

Salmonella enterica serovar Typhimurium Sequence Type (ST) 313 is a major cause of invasive non-Typhoidal salmonellosis in sub-Saharan Africa. No animal reservoir has been identified, and it has been suggested that ST313 is adapted to humans and transmission may occur via person-to-person spread. Here, we show that ST313 cause severe invasive infection in chickens as well as humans. Oral infection of chickens with ST313 isolates D23580 and Q456 resulted in rapid infection of spleen and liver with all birds infected at these sites by 3 days post-infection. In contrast, the well-defined ST19 S. Typhimurium isolates F98 and 4/74 were slower to cause invasive disease. Both ST19 and ST313 caused hepatosplenomegaly, and this was most pronounced in the ST313-infected animals. At 3 and 7 days post-infection, colonization of the gastrointestinal tract was lower in birds infected with the ST313 isolates compared with ST19. Histological examination and expression of CXCL chemokines in the ileum showed that both D23580 (ST313) and 4/74 (ST19) strains caused increased CXCL expression at 3 days post-infection, and this was significantly higher in the ileum of D23580 vs 4/74 infected birds. At 7 days post-infection, reduced chemokine expression occurred in the ileum of the D23580 but not 4/74-infected birds. Histological analysis showed that D23580 infection resulted in rapid inflammation and pathology including villous flattening and fusion at 3 days post-infection, and subsequent resolution by 7 days. In contrast, 4/74 induced less inflammation and pathology at 3 days post-infection. The data presented demonstrate that ST313 is capable of causing invasive disease in a non-human host. The rapid invasive nature of infection in the chicken, coupled with lower gastrointestinal colonization, supports the hypothesis that ST313 is a distinct pathovariant of S. Typhimurium that has evolved to become a systemic pathogen that can cause disease in several hosts.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Viable counts of Salmonella Typhimurium ST313 and ST19 in cecal contents and spleen following oral infection of the chicken.
Viable counts (CFU/g) of cecal content (A) and spleen (B) at 3 and 7 days post-oral infection of two week old commercial egg laying chicks with 108 CFU ST313 (D23580, Q456) and ST19 (F98, 4/74) S. Typhimurium. Counts are shown as individual birds with the bar representing the median value. Five birds from each group were killed for sampling at each time point (n = 5) in each experiment. Data shown for D23580 and 4/74 (n = 10 per time point) is combined data for two separately repeated experiments. Statistical comparison was made using a Kruskal-Wallis test. *, P<0.05. **, P<0.01. ***, P<0.001.
Figure 2
Figure 2. Expression of CXCL chemokines in the chicken gastrointestinal tract following infection with S. Typhimurium ST313 or ST19.
Expression of the chemokines CXCLi1 and CXCLi2, considered to be orthologous to mammalian IL-8, were determined by qRT-PCR. Relative expression in ceca (Figure 2A) and ileum (Figure 2B) of ST313 (D23580) and ST19 (4/74) infected groups were made in comparison to mock-infected control birds by (2−[ΔΔCT]) method. Data is expressed as fold changes in expression in individual birds with the bar representing the mean value. Expression was determined in five birds per group at each time point. Statistical comparison was made by ANOVA. *, P<0.05. **, P<0.01.
Figure 3
Figure 3. Histopathological changes in the ileum following infection with S. Typhimurium ST313 or ST19.
Photomicrographs (×ばつ400 magnification) of histological changes in H and E stained fixed ileal tissue following infection with S. Typhimurium ST313 show a rapid inflammation at three days post-infection leading to villus fusion and flattening accompanied by infiltration of lymphocytes and polymorphonucelar cells (heterophils) and crypt hyperplasia. By seven days post-infection, inflammation and pathology is reduced. In birds infected with ST19 (4/74) S. Typhimurium the inflammatory process appears slower with limited inflammation at three days post infection, but substantial damage to the structure of the ileum at seven days post-infection with a high degree of villus damage and large areas of inflammatory infiltration. Arrows indicate heterophil influxes. Scale bar = 100 μm.
Figure 4
Figure 4. Histopathological changes in liver and spleen following infection with S. Typhimurium ST313 or ST19.
Photomicrographs (×ばつ400 magnification) of histological changes in H and E in fixed splenic and liver sections at seven days post infection. Both ST313 (D23580) and ST19 (4/74) infection result in hepatosplenomegaly as shown by the influx of inflammatory cells, and this is greater in ST313 infection. Infection also results in granuloma-like lesions typical of avian salmonellosis, which are larger and more numerous in the ST313 infected birds. Black arrows indicate granuloma-like lesions and white arrows indicate heterophil influxes. Scale bar = 100 μm.

References

    1. Feasey NA, Dougan G, Kingsley RA, Heyderman RS, Gordon MA (2012) Invasive non-typhoidal salmonella disease: an emerging and neglected tropical disease in Africa. Lancet 379: 2489–2499. - PMC - PubMed
    1. Gordon MA (2011) Invasive nontyphoidal Salmonella disease: epidemiology, pathogenesis and diagnosis. Current opinion in infectious diseases 24: 484–489. - PMC - PubMed
    1. Okoro CK, Kingsley RA, Connor TR, Harris SR, Parry CM, et al. (2012) Intracontinental spread of human invasive Salmonella Typhimurium pathovariants in sub-Saharan Africa. Nature genetics 44: 1215–1221. - PMC - PubMed
    1. Kingsley RA, Msefula CL, Thomson NR, Kariuki S, Holt KE, et al. (2009) Epidemic multiple drug resistant Salmonella Typhimurium causing invasive disease in sub-Saharan Africa have a distinct genotype. Genome research 19: 2279–2287. - PMC - PubMed
    1. Thomson NR, Clayton DJ, Windhorst D, Vernikos G, Davidson S, et al. (2008) Comparative genome analysis of Salmonella Enteritidis PT4 and Salmonella Gallinarum 287/91 provides insights into evolutionary and host adaptation pathways. Genome research 18: 1624–1637. - PMC - PubMed

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