Abstract
Salmonella enterica is an important enteric pathogen and its various serovars are involved in causing both systemic and intestinal diseases in humans and domestic animals. The emergence of multidrug-resistant strains of Salmonella leading to increased morbidity and mortality has further complicated its management. Live attenuated vaccines have been proven superior over killed or subunit vaccines due to their ability to induce protective immunity. Of the various strategies used for the generation of live attenuated vaccine strains, focus has gradually shifted towards manipulation of virulence regulator genes. Hfq is a RNA chaperon which mediates the binding of small RNAs to the mRNA and assists in post-transcriptional gene regulation in bacteria. In this study, we evaluated the efficacy of the Salmonella Typhimurium Δhfq strain as a candidate for live oral vaccine in murine model of typhoid fever. Salmonella hfq deletion mutant is highly attenuated in cell culture and animal model implying a significant role of Hfq in bacterial virulence. Oral immunization with the Salmonella hfq deletion mutant efficiently protects mice against subsequent oral challenge with virulent strain of Salmonella Typhimurium. Moreover, protection was induced upon both multiple as well as single dose of immunizations. The vaccine strain appears to be safe for use in pregnant mice and the protection is mediated by the increase in the number of CD4+ T lymphocytes upon vaccination. The levels of serum IgG and secretory-IgA in intestinal washes specific to lipopolysaccharide and outer membrane protein were significantly increased upon vaccination. Furthermore, hfq deletion mutant showed enhanced antigen presentation by dendritic cells compared to the wild type strain. Taken together, the studies in murine immunization model suggest that the Salmonella hfq deletion mutant can be a novel live oral vaccine candidate.
Highlights
Salmonellae are Gram-negative, facultative intracellular pathogens, causing variety of diseases in multiple hosts with different disease outcome
We compared the growth of the hfq deletion mutant with that of the STM-WT in rich media (LB) and defined media
While the number of viable bacteria was found to be same for equal OD of both the cultures, the hfq mutant reached stationary phase at later time than STM-WT in both Luria Broth (LB) as well as in the minimal media
Summary
Salmonellae are Gram-negative, facultative intracellular pathogens, causing variety of diseases in multiple hosts with different disease outcome. The genus Salmonella is composed of two distinct species: Salmonella bongori, a commensal of cold-blooded animals and Salmonella enterica. Enterica) are responsible for the vast majority of the Salmonella infections in warm-blooded animals [2]. These serotypes differ widely in a variety of features, most notably in their host range, severity and type of disease they typically cause. S. enterica serovar Typhimurium is an important cause of food poisoning and human gastroenteritis and has added significance as a model of human typhoid fever in mice. S.Typhimurium infection is often fatal if remained untreated in immuno-compromised patients [2,3]
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