Antifungal defense of probiotic Lactobacillus rhamnosus GG is mediated by blocking adhesion and nutrient depletion

Abstract

Candida albicans is an inhabitant of mucosal surfaces in healthy individuals but also the most common cause of fungal nosocomial blood stream infections, associated with high morbidity and mortality. As such life-threatening infections often disseminate from superficial mucosal infections we aimed to study the use of probiotic Lactobacillus rhamnosus GG (LGG) in prevention of mucosal C. albicans infections. Here, we demonstrate that LGG protects oral epithelial tissue from damage caused by C. albicans in our in vitro model of oral candidiasis. Furthermore, we provide insights into the mechanisms behind this protection and dissect direct and indirect effects of LGG on C. albicans pathogenicity. C. albicans viability was not affected by LGG. Instead, transcriptional profiling using RNA-Seq indicated dramatic metabolic reprogramming of C. albicans. Additionally, LGG had a significant impact on major virulence attributes, including adhesion, invasion, and hyphal extension, whose reduction, consequently, prevented epithelial damage. This was accompanied by glucose depletion and repression of ergosterol synthesis, caused by LGG, but also due to blocked adhesion sites. Therefore, LGG protects oral epithelia against C. albicans infection by preventing fungal adhesion, invasion and damage, driven, at least in parts, by metabolic reprogramming due to nutrient limitation caused by LGG.

The role of Lactobacillus species in the control of Candida via biotrophic interactions

“…RNA-Seq of C. albicans gene expression in response to a TR146 cell monolayer, which was preincubated with L. rhamnosus GG revealed upregulation of genes involved in fatty acid catabolism, glyoxylate cycle and gluconeogenesis and downregulation of glycolysis and ergosterol biosynthesis genes [136]. Another study investigating L. reuteri RC-14 and L. rhamnosus GR-1 co-culture found an upregulation of glycolysis and a reduced expression of genes relating to gluconeogenesis [105].…”

“…The use of this biosurfactants could be developed further as a potential new coating material for medical devices to minimize Candida infections [134]. In general, supernatants of different Lactobacillus species were found to reduce adhesion of C. albicans to HeLa cells (L. crispatus, L. gasseri) [125], to plastic surface (L. paracasei) [135], as well as to TR146 cells (L. rhamnosus) [136].…”

“…as potent novel probiotics. Furthermore, one study was conducted on cell layer surface, while the other one on an abiotic surface [105,136]. This could be an indicator for the importance of proper in vitro systems, mimicking the actual environment as close as possible.…”

Лечение Функциональных Гастроинтестинальных Расстройств У Детей Раннего Возраста

“…Неодмінною перевагою пробіотиків, до складу яких входить LGG, є безпека використання без виникнення будь-яких несприятливих побічних ефектів серед різних вікових груп пацієнтів -від новонароджених до людей похилого віку (Floch et al, 2008). Використання LGG у вагітних жінок і новонароджених з метою запобігання колонізації Candida є вагомим доказом високого профілю безпеки пробіотика [22,25]. Доведено, що ризик розвитку бактеріємії при застосуванні LGG навіть у новонароджених становить менше ніж 1 випадок на 1 млн [24].…”

Development and characterization of a 3D oral mucosa model as a tool for host-pathogen interactions

“…Microorganisms suspensions were placed on top of the reconstituted in vitro oral mucosa tissue in antibiotic-free KGM-Gold medium containing growth factors and were incubated in a CO 2 chamber at 37°C. KGM-Gold medium is suitable for microorganism grows (Mohiti-Asli et al, 2014;Mailänder-Sánchez et al, 2017). After 8 and 16 h of incubation, biopsy specimens were collected from infected and uninfected tissues, and stained with hematoxylin and eosin (HE).…”