Removal of Antibiotic Resistance Gene-Carrying Plasmids from Lactobacillus reuteri ATCC 55730 and Characterization of the Resulting Daughter Strain, L . reuteri DSM 17938

Abstract

The spread of antibiotic resistance in pathogens is primarily a consequence of the indiscriminate use of antibiotics, but there is concern that food-borne lactic acid bacteria may act as reservoirs of antibiotic resistance genes when distributed in large doses to the gastrointestinal tract. Lactobacillus reuteri ATCC 55730 is a commercially available probiotic strain which has been found to harbor potentially transferable resistance genes. The aims of this study were to define the location and nature of ␤-lactam, tetracycline, and lincosamide resistance determinants and, if they were found to be acquired, attempt to remove them from the strain by methods that do not genetically modify the organism before subsequently testing whether the probiotic characteristics were retained. No known ␤-lactam resistance genes was found, but penicillin-binding proteins from ATCC 55730, two additional resistant strains, and three sensitive strains of L. reuteri were sequenced and comparatively analyzed. The ␤-lactam resistance in ATCC 55730 is probably caused by a number of alterations in the corresponding genes and can be regarded as not transferable. The strain was found to harbor two plasmids carrying tet(W) tetracycline and lnu(A) lincosamide resistance genes, respectively. A new daughter strain, L. reuteri DSM 17938, was derived from ATCC 55730 by removal of the two plasmids, and it was shown to have lost the resistances associated with them. Direct comparison of the parent and daughter strains for a series of in vitro properties and in a human clinical trial confirmed the retained probiotic properties of the daughter strain.

Diarrhea in Preschool Children and Lactobacillus reuteri: A Randomized Controlled Trial

“…Two of the studies reveal similar outcome on diarrhea with L reuteri ATCC 55730 and L reuteri DSM 17938 strains, which are closely related, 10 but to establish evidence-based recommendations for the use of L reuteri DSM 17938 for the prevention of infectious disease in day care centers, similar and independent trials with this strain are needed to support a systematic review of outcomes with the same intervention. The current study was designed therefore to evaluate the efficacy of prophylactic use of L reuteri DSM 17938 in reducing the frequency and duration of diarrheal episodes and other health outcomes in Mexican children in the day care setting and further, to assess cost-effectiveness of the intervention.…”

Assessment of Antibiotic Resistance in Probiotic Lactobacilli

“…BioGaia concluded that L. reuteri strain DSM 17938, except for the deletion of plasmids pLR581 and pLR585, was substantially equivalent to its parent strain L. reuteri ATCC 55730. Additionally, BioGaia concluded that the evidence demonstrating the safety of strain ATCC 55730 is equally applicable to strain DSM 17938 (Rosander et al, 2008). Hummel et al determined antibiotic resistances and to verify these at the genetic level according to the QPS system.…”

Lactobacillus reuteri DSM 17938 differentially modulates effector memory T cells and Foxp3+ regulatory T cells in a mouse model of necrotizing enterocolitis

“…Lactobacillus reuteri DSM 17938 (LR17938) was derived from L. reuteri ATCC 55730, a component of a Peruvian mother's breast milk. Two plasmids harboring antibiotic resistance genes were removed from strain 55730 to obtain strain 17938 (46), which inhibits pathogen growth and modulates the immune system. We have shown that feeding LR17938 to newborn rats produced a strong anti-inflammatory effect (28,29), reducing the incidence and severity of NEC (29) while increasing the frequency of Treg cells in the intestinal mucosa (27).…”