Protective effect of Lactobacillus casei strain Shirota against lethal infection with multi-drug resistant Salmonella enterica serovar Typhimurium DT104 in mice

Abstract

Aims: The anti‐infectious activity of lactobacilli against multi‐drug resistant Salmonella enterica serovar Typhimurium DT104 (DT104) was examined in a murine model of an opportunistic antibiotic‐induced infection. Methods and Results: Explosive intestinal growth and subsequent lethal extra‐intestinal translocation after oral infection with DT104 during fosfomycin (FOM) administration was significantly inhibited by continuous oral administration of Lactobacillus casei strain Shirota (LcS), which is naturally resistant to FOM, at a dose of 108 colony‐forming units per mouse daily to mice. Comparison of the anti‐Salmonella activity of several Lactobacillus type strains with natural resistance to FOM revealed that Lactobacillus brevis ATCC 14869T, Lactobacillus plantarum ATCC 14917T, Lactobacillus reuteri JCM 1112T, Lactobacillus rhamnosus ATCC 7469T and Lactobacillus salivarius ATCC 11741T conferred no activity even when they obtained the high population levels almost similar to those of the effective strains such as LcS, Lact. casei ATCC 334T and Lactobacillus zeae ATCC 15820T. The increase in concentration of organic acids and maintenance of the lower pH in the intestine because of Lactobacillus colonization were correlated with the anti‐infectious activity. Moreover, heat‐killed LcS was not protective against the infection, suggesting that the metabolic activity of lactobacilli is important for the anti‐infectious activity. Conclusion: These results suggest that certain lactobacilli in combination with antibiotics may be useful for prophylaxis against opportunistic intestinal infections by multi‐drug resistant pathogens, such as DT104. Significance and Impact of the Study: Antibiotics such as FOM disrupt the metabolic activity of the intestinal microbiota that produce organic acids, and that only probiotic strains that are metabolically active in vivo should be selected to prevent intestinal infection when used clinically in combination with certain antibiotics.

Anti-Infective Activities of Lactobacillus Strains in the Human Intestinal Microbiota: from Probiotics to Gastrointestinal Anti-Infectious Biotherapeutic Agents

“…casei Shirota displays an antagonistic activity against the multidrug-resistant S. Typhimurium strain DT104 in a fosfomycintreated murine model, since the intestinal growth of the pathogen and its subsequent lethal extraintestinal translocation were inhib- ited in a manner correlated with intestinal colonization by the Lactobacillus strain (135). This observation is interesting in the light of the currently increasing public health problem of multidrug-resistant enterovirulent bacteria (255,256) and persister cells (257,258).…”

“…Heat treatment of probiotic Lactobacillus strains results in a marked decrease of antimicrobial activity (320) compared to that of the parental live strains (135,139,215,298). Heat-treated Lactobacillus strains cannot be considered to be probiotics (321), because the definition of probiotics states that the strains are alive (69).…”

Hypocholesterolemic and Growth Promoting Effects of <i>Lactobacillus plantarum</i> AK Isolated from a Nigerian Fermented Cereal Product on Rats Fed High Fat Diet

“…Recently, there has been renewed interest in lactic acid bacteria (LAB) particularly Lactobacillus spp which are generally recognized as safe (GRAS) and have been linked to their contribution to health such as immunomodulation, anticarcinogenic properties and hypocholesterolemic properties [11][12][13][14]. There has been accumulating evidence that the presence Lactobacillus in sufficient amounts is associated with the lowering of serum cholesterol levels in experimental animals [13,15] though this is not always proven in humans [16].…”

Bioengineered probiotics, a strategic approach to control enteric infections

“…41 L. casei Shirota strain also protected mice against lethal infection with multi-drug resistant S. Typhimurium DT104. 42 Besides the antimicrobial effects, probiotics also increased the performance employed to create bioengineered probiotics. Paton and colleagues 61 cloned and expressed toxin-specific host cell receptor on probiotic E. coli thus creating a competitive environment for toxin binding to host cells.…”