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Distinct stages during colonization of the mouse gastrointestinal tract by Candida albicans.

Prieto D, Pla J - Front Microbiol (2015)

Bottom Line: Candida albicans is a member of the human microbiota, colonizing both the vaginal and gastrointestinal tracts.This yeast is devoid of a life style outside the human body and the mechanisms underlying the adaptation to the commensal status remain to be determined.We show that long term (15 days) colonizing cells have increased fitness in the gut niche over those grown in vitro or residing in the gut for 1-3 days.

View Article: PubMed Central - PubMed

Affiliation: Departamento de MicrobiologĂ­a II, Facultad de Farmacia, Universidad Complutense de Madrid Madrid, Spain.

ABSTRACT
Candida albicans is a member of the human microbiota, colonizing both the vaginal and gastrointestinal tracts. This yeast is devoid of a life style outside the human body and the mechanisms underlying the adaptation to the commensal status remain to be determined. Using a model of mouse gastrointestinal colonization, we show here that C. albicans stably colonizes the mouse gut in about 3 days starting from a dose as low as 100 cells, reaching steady levels of around 10(7) cells/g of stools. Using fluorescently labeled strains, we have assessed the competition between isogenic populations from different sources in cohoused animals. We show that long term (15 days) colonizing cells have increased fitness in the gut niche over those grown in vitro or residing in the gut for 1-3 days. Therefore, two distinct states, proliferation and adaptation, seem to exist in the adaptation of this fungus to the mouse gut, a result with potential significance in the prophylaxis and treatment of Candida infections.

No MeSH data available.


Related in: MedlinePlus

Decay of colonization of differentC. albicanspopulations after antibiotic removal. Antibiotic treatment was replaced with sterile water in each group (n = 4) on day 0 (Ca-n, open circles), day 2 (Ca-gS, gray squares) or day 23 (Ca-gL, black triangles) from the inoculation of 107 cells of C. albicans. Each symbol represents data from an individual mouse. (A) Evolution of fungal loads in stools (log CFU per gram) along 21 days after the antibiotic treatment was removed. (B) Ratios of fungal levels (CFU per gram) in relation to the day when antibiotics was removed (day 0). *p < 0.05, **p < 0.01, ***p < 0.001.
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Figure 2: Decay of colonization of differentC. albicanspopulations after antibiotic removal. Antibiotic treatment was replaced with sterile water in each group (n = 4) on day 0 (Ca-n, open circles), day 2 (Ca-gS, gray squares) or day 23 (Ca-gL, black triangles) from the inoculation of 107 cells of C. albicans. Each symbol represents data from an individual mouse. (A) Evolution of fungal loads in stools (log CFU per gram) along 21 days after the antibiotic treatment was removed. (B) Ratios of fungal levels (CFU per gram) in relation to the day when antibiotics was removed (day 0). *p < 0.05, **p < 0.01, ***p < 0.001.

Mentions: It is known that modification of the bacterial microbiota is needed to allow a stable colonization of C. albicans (Koh et al., 2008). Our colonization protocol is based on application of a specific antibiotic regime to the mice via the drinking water (Wiesner et al., 2001) and when removed, fungal loads decrease (Prieto et al., 2014) allowing efficient removal of C. albicans from the mouse gut. We wondered if this decline would occur similarly to gut-adapted or non-adapted populations of C. albicans. We used for this purpose cells obtained from in vitro standard laboratory growth conditions (that we call Ca-n, for non-adapted), and cells already present in the mouse gut (Ca-g, for gut adapted). We also distinguished between short-term adapted (Ca-gS) cells for those present in the gut for 2 days and long-term adapted (Ca-gL) when they have established in the gut for 2 or more weeks (see Table 1 and Materials and Methods). We therefore treated 3 groups of mice with antibiotics for 4 days and afterwards 107C. albicans cells were inoculated to each individual. Antibiotic therapy was removed from experimental groups at different time points: group 1 mice lacked antibiotics in drinking water immediately after inoculation (day 0), in group 2, antibiotic therapy was removed 2 days after inoculation (Ca-gS) while in group 3 cells were allowed to colonize for 23 days (Ca-gL). After oral antibiotics were removed, fungal loads on stools were analyzed at different days (0, 1, 8, 13, and 21). To assess the colonization decrease rate and be able to compare the behavior of different groups, we calculated linear regression of fungal loads (log CFU/g) at different time points (Figure 2A). Ca-gL group showed the lowest fall of colonization (0.117 log units per day), while groups Ca-gS and Ca-n displayed slopes of 0.263 and 0.209, respectively, roughly inversely correlating with colonization time. Actually, only Ca-gL group linear regression differed significantly from the other two groups (p < 0.01 for Ca-n and p < 0.001 for Ca-gS). Ca-gS and Ca-n did not show a significant different behavior. Since each group presents a different colonization level after antibiotic removal, we calculated ratios of fungal loads referring to the value attained at day 0 (Figure 2B). At day 1, all groups present similar log2 values close to 0, indicating that no important changes had affected the C. albicans populations yet. All groups experienced an important drop in fungal loads in the following days. This effect was less pronounced in Ca-gL group and, interestingly, much more in Ca-gS population. The latter was significantly different from the other two groups, on both days 8 and 13. However, on day 21 no significant differences among groups were observed.


Distinct stages during colonization of the mouse gastrointestinal tract by Candida albicans.

Prieto D, Pla J - Front Microbiol (2015)

Decay of colonization of differentC. albicanspopulations after antibiotic removal. Antibiotic treatment was replaced with sterile water in each group (n = 4) on day 0 (Ca-n, open circles), day 2 (Ca-gS, gray squares) or day 23 (Ca-gL, black triangles) from the inoculation of 107 cells of C. albicans. Each symbol represents data from an individual mouse. (A) Evolution of fungal loads in stools (log CFU per gram) along 21 days after the antibiotic treatment was removed. (B) Ratios of fungal levels (CFU per gram) in relation to the day when antibiotics was removed (day 0). *p < 0.05, **p < 0.01, ***p < 0.001.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4525673&req=5

Figure 2: Decay of colonization of differentC. albicanspopulations after antibiotic removal. Antibiotic treatment was replaced with sterile water in each group (n = 4) on day 0 (Ca-n, open circles), day 2 (Ca-gS, gray squares) or day 23 (Ca-gL, black triangles) from the inoculation of 107 cells of C. albicans. Each symbol represents data from an individual mouse. (A) Evolution of fungal loads in stools (log CFU per gram) along 21 days after the antibiotic treatment was removed. (B) Ratios of fungal levels (CFU per gram) in relation to the day when antibiotics was removed (day 0). *p < 0.05, **p < 0.01, ***p < 0.001.
Mentions: It is known that modification of the bacterial microbiota is needed to allow a stable colonization of C. albicans (Koh et al., 2008). Our colonization protocol is based on application of a specific antibiotic regime to the mice via the drinking water (Wiesner et al., 2001) and when removed, fungal loads decrease (Prieto et al., 2014) allowing efficient removal of C. albicans from the mouse gut. We wondered if this decline would occur similarly to gut-adapted or non-adapted populations of C. albicans. We used for this purpose cells obtained from in vitro standard laboratory growth conditions (that we call Ca-n, for non-adapted), and cells already present in the mouse gut (Ca-g, for gut adapted). We also distinguished between short-term adapted (Ca-gS) cells for those present in the gut for 2 days and long-term adapted (Ca-gL) when they have established in the gut for 2 or more weeks (see Table 1 and Materials and Methods). We therefore treated 3 groups of mice with antibiotics for 4 days and afterwards 107C. albicans cells were inoculated to each individual. Antibiotic therapy was removed from experimental groups at different time points: group 1 mice lacked antibiotics in drinking water immediately after inoculation (day 0), in group 2, antibiotic therapy was removed 2 days after inoculation (Ca-gS) while in group 3 cells were allowed to colonize for 23 days (Ca-gL). After oral antibiotics were removed, fungal loads on stools were analyzed at different days (0, 1, 8, 13, and 21). To assess the colonization decrease rate and be able to compare the behavior of different groups, we calculated linear regression of fungal loads (log CFU/g) at different time points (Figure 2A). Ca-gL group showed the lowest fall of colonization (0.117 log units per day), while groups Ca-gS and Ca-n displayed slopes of 0.263 and 0.209, respectively, roughly inversely correlating with colonization time. Actually, only Ca-gL group linear regression differed significantly from the other two groups (p < 0.01 for Ca-n and p < 0.001 for Ca-gS). Ca-gS and Ca-n did not show a significant different behavior. Since each group presents a different colonization level after antibiotic removal, we calculated ratios of fungal loads referring to the value attained at day 0 (Figure 2B). At day 1, all groups present similar log2 values close to 0, indicating that no important changes had affected the C. albicans populations yet. All groups experienced an important drop in fungal loads in the following days. This effect was less pronounced in Ca-gL group and, interestingly, much more in Ca-gS population. The latter was significantly different from the other two groups, on both days 8 and 13. However, on day 21 no significant differences among groups were observed.

Bottom Line: Candida albicans is a member of the human microbiota, colonizing both the vaginal and gastrointestinal tracts.This yeast is devoid of a life style outside the human body and the mechanisms underlying the adaptation to the commensal status remain to be determined.We show that long term (15 days) colonizing cells have increased fitness in the gut niche over those grown in vitro or residing in the gut for 1-3 days.

View Article: PubMed Central - PubMed

Affiliation: Departamento de MicrobiologĂ­a II, Facultad de Farmacia, Universidad Complutense de Madrid Madrid, Spain.

ABSTRACT
Candida albicans is a member of the human microbiota, colonizing both the vaginal and gastrointestinal tracts. This yeast is devoid of a life style outside the human body and the mechanisms underlying the adaptation to the commensal status remain to be determined. Using a model of mouse gastrointestinal colonization, we show here that C. albicans stably colonizes the mouse gut in about 3 days starting from a dose as low as 100 cells, reaching steady levels of around 10(7) cells/g of stools. Using fluorescently labeled strains, we have assessed the competition between isogenic populations from different sources in cohoused animals. We show that long term (15 days) colonizing cells have increased fitness in the gut niche over those grown in vitro or residing in the gut for 1-3 days. Therefore, two distinct states, proliferation and adaptation, seem to exist in the adaptation of this fungus to the mouse gut, a result with potential significance in the prophylaxis and treatment of Candida infections.

No MeSH data available.


Related in: MedlinePlus