Genomic evaluation of a case of Lacticaseibacillus rhamnosus endocarditis: comparison with commercial yogurt isolates and examination of global population structure

Abstract

Probiotics, including yogurt commonly containing bacteria of the Lactobacillus group, are widely used to promote microbiome health and to prevent gastrointestinal or other infections, especially in the setting of antibiotic use. Rarely, however, Lactobacillus bacteria have caused invasive or severe infections in patients. In this report, we present a patient with fatal Lacticaseibacillus bacteremia and endocarditis who frequently consumed yogurt. Whole genome sequencing identified the patients bloodstream isolate as Lacticaseibacillus (formerly Lactobacillus) rhamnosus, and sequencing of Lactobacillus isolates from selected commercial yogurt preparations revealed one isolate nearly identical to the patients isolate, differing by only one nucleotide (adenine to guanine substitution leading to a M1A amino acid change in the start codon of the nrdR gene). To place these sequences into broader context of L. rhamnosus strains, we compared them to 602 L. rhamnosus genome sequences publicly available through the National Center for Biotechnology Information repository. Both isolates belonged to a clade, identified in this report as clade YC, composed of mostly gastrointestinal isolates from healthy individuals, some of which also differed by only a single nucleotide from the patients isolate. Members of clade YC had only rarely been previously identified in invasive infections. In summary, the Lacticaseibacillus strain causing this patients infection may have originated from a commercial dairy product or from the commensal flora of his gastrointestinal tract. This study demonstrates that whole genome sequencing may be insufficient to reliably determine the source of invasive infections caused by L. rhamnosus. IMPORTANCEActive culture and probiotic foods and supplements are often used to promote gut health. Though largely considered safe for human consumption, there are rare reports of severe infections linked to bacterial species used in these products. Using whole genome sequencing, we examined a case of fatal infection with Lacticaseibacillus rhamnosus in the patients blood. By comparing the bacterial genome sequence from the patient to strains cultured from 4 commercial yogurt samples and 602 publicly available sequences of L. rhamnosus from around the world, we found that it was nearly identical to one of the yogurt strains and equally similar to other strains from both probiotics and healthy individuals gastrointestinal tracts. These findings show that even with whole genome sequencing it can be difficult to determine the source of an invasive L. rhamnosus infection, whether from recent consumption of a probiotic or dairy product versus from the gastrointestinal microbiome.