Abstract

An experimental infection with Salmonella enterica subsp. enterica serovar Typhimurium was evaluated in gnotobiotic mice previously exposed to a plasmid-free non-pathogenic Escherichia coli (EMO strain). Mice were exposed to EMO (experimental) or not (control) 10 days before challenge with Salmonella Typhimurium (10(2) colony forming units (CFU)/mouse). Survival after challenge was higher (P < 0.05) in the experimental group (16%) than in the control animals (0%). Histopathological examination of the colon and ileum mucosa of the experimental group showed less extensive lesions such as edema, cell inflammatory infiltration and hyperemia. The epithelial cells of the mucosal surface and the production of the mucous layer were also better preserved in the experimental group. The population levels of Salmonella Typhimurium in the feces were initially 10-fold lower (P < 0.05) in the experimental groups. However, 3 days after challenge both experimental and control groups showed similar population levels ranging from 10(8) to 10(9) CFU/g of feces. The intestinal contents of total and anti-Salmonella Typhimurium sIgA were higher in the experimental groups 10 days after inoculation of E. coli EMO strain. Translocation of Salmonella Typhimurium to the spleen was 10-fold lower (P < 0.05) in the experimental group only on day 3 after infection. This was not related to an increase in the bacterial blood clearance of the animals, as shown by experimental venous challenge with E. coli B41. In conclusion, treatment of mice with E. coli EMO strain promoted a relative protection against experimental infection with Salmonella Typhimurium. This protection was not due to the reduction of the population of pathogens in the intestine but was probably related to stimulation of the immune response.

Highlights

  • Control and treatment of infectious diseases frequently are challenged by the development of antibiotic resistance, increased frequency of opportunistic infections in immunocompromised patients, and the emergence of new types of pathogens

  • Evaluation of the mortality of gnotobiotic mice previously associated with E. coli EMO strain and challenged with Salmonella Typhimurium showed that E. coli was unable, by itself, to confer complete protection against the pathogen (Figure 1)

  • In order to better understand the mechanisms involved in the observed protective effect, we first determined if the E. coli EMO strain antagonized Salmonella Typhimurium in vivo

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Summary

Introduction

Control and treatment of infectious diseases frequently are challenged by the development of antibiotic resistance, increased frequency of opportunistic infections in immunocompromised patients, and the emergence of new types of pathogens. These factors, as well as inappropriate therapy, result in an increased exposure of the population to antibiotics, which, in turn, select resistant pathogenic strains. The World Health Organization (WHO) held a conference [1] to discuss this increase in antibiotic resistance, which today is “a major public health problem in both developed and developing countries throughout the world” With this in mind, the WHO recommends global programs to reduce the use of antibiotics and increased efforts to prevent disease through the development of newer, more effective and safer therapies. The use of a gnotobiotic animal model with a simplified intestinal microbial status allows the in vivo observation of interrelationships between microorganisms such as a probiotic and a pathogenic bacterium as well as between these microorganisms and the host

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