Interstrain Variability of Human Vaginal Lactobacillus crispatus for Metabolism of Biogenic Amines and Antimicrobial Activity against Urogenital Pathogens

Abstract

Lactobacillus crispatus is the dominant species in the vagina of many women. With the potential for strains of this species to be used as a probiotic to help prevent and treat dysbiosis, we investigated isolates from vaginal swabs with Lactobacillus-dominated and a dysbiotic microbiota. A comparative genome analysis led to the identification of metabolic pathways for synthesis and degradation of three major biogenic amines in most strains. However, targeted metabolomic analysis of the production and degradation of biogenic amines showed that certain strains have either the ability to produce or to degrade these compounds. Notably, six strains produced cadaverine, one produced putrescine, and two produced tyramine. These biogenic amines are known to raise vaginal pH, cause malodour, and make the environment more favourable to vaginal pathogens. In vitro experiments confirmed that strains isolated from women with a dysbiotic vaginal microbiota have higher antimicrobial effects against the common urogenital pathogens Escherichia coli and Enterococcus faecium. The results indicate that not all L. crispatus vaginal strains appear suitable for probiotic application and the basis for selection should not be only the overall composition of the vaginal microbiota of the host from which they came, but specific biochemical and genetic traits.

Why Are Bifidobacteria Important for Infants?

“…With ethical issues surrounding the supplementation of live microorganisms to infants, such an intervention would require proof of the strain's necessity in addition to rigorous safety testing. We have recently shown for Lactobacillus crispatus that metabolomic analysis can identify strains appropriate or not for probiotic applications to improve vaginal health [30]. It might not seem to be a relevant topic for a female infant but debilitating urinary tract infections can occur at that age [31].…”

“…To date, some evidence exists to show that probiotic supplementation is sufficient to normalize the gut microbiota of C-section babies [61,62]. If this is true, then the early intervention of well-selected probiotic strains in these infants may provide a healthier start to development and prevent some of the chronic illnesses associated with microbial dysbiosis later in life [15,17,30,31,39,60]. However, investigations to elucidate which strain(s) are most effective remain to be conducted.…”

The Two-Way Interaction between the Molecules That Cause Vaginal Malodour and Lactobacilli: An Opportunity for Probiotics

“…We previously characterized several clinical L. crispatus strains in terms of their potential to degrade and/or produce biogenic amines, while all of them have the genes for both functions, only a few were able to reduce the amount of amines in growth media. This formed the basis for selecting the strains for the present study [13]. Of significant note, L. crispatus ATCC 33820 and five vaginal L. crispatus isolates showed statistically significant reduction of putrescine, cadaverine and tyramine within 24 h. The exception was strain RL12 which increased tyramine.…”

“…It is unclear if this adaptation is pH-or metabolite-mediated. Previous studies have shown that the expression of the arginine deiminase pathway (which plays a major role in the metabolism of cadaverine and putrescine [13]) is pH-dependent in other Lactobacillus species [19]. Future studies should focus on global metabolomics and transcriptomic analyses that might identify which metabolic pathways are different between both groups and could therefore be causing these differences.…”

“…Previous studies have suggested that BAs are produced by some pathogens and they act as virulence factors that increase the urogenital pH, reduce production of lactic acid, and lower the abundance of lactobacilli [11,12]. Previously, several strains of L. crispatus have exhibited the potential to degrade BAs [13]. In the present study, five clinical isolates of L. crispatus were tested for their ability to reduce BAs, along with the type-strain L. crispatus ATCC 33820, LGR-1, and LRC-14.…”