Lactobacillus species in the female urogenital system act as a barrier
to infection and contribute to the control of the vaginal microbiota by
competing with other microorganisms for adherence to epithelial cells,
displacing pathogen biofilm [
12,
13], and/or inhibiting the growth of potential pathogens [
14–
16]. Hence the use of probiotic strains of
Lactobacilli is potentially interesting both as preventive and
curative agents.
Unlike the use of vaginal epithelial cells
collected from healthy premenopausal women, assays
performed with immortalized epithelial cell lines, which closely resemble the
epithelial differentiation patterns of normal human tissues, are more accurate
for standardizing tested bacterial adherence and allow comparison of different
research approaches. The three epithelial cell lines tested in this study were
developed from normal human vagina, ectocervix, and endocervix tissue, and
their characteristics closely resembled those of their tissues of origin and
primary cultures [
11]. We can thus speculate that adhesion assays performed with this
material reproduce more faithfully the in vivo situation than experiments
performed with any cell line derived from human carcinoma of the lower genital
tract mucosa. This is particularly
important when comparing bacterial strains belonging to the complex
Lactobacillus genus that includes
bacterial strains with highly specific characteristics. Using these cell lines,
we observed specific adhesion of an
L.
rhamnosus strain, Lcr35, previously selected for its probiotic features [
8–
10]. Adhesion occurred even at a low MOI (1:1) and within less than 1 hour
of contact, which corresponds to a highly dynamic process.
Adhesion of Lcr35 to vaginal epithelial cells
would allow colonization of the vaginal mucosa and therefore could limit the
overgrowth of pathogens, but the second main property of a potential probiotic
used as a therapeutic agent against pathogenic microorganisms is direct impairment
of their growth. In this study, we demonstrated that Lcr35 showed bactericidal
activity against both
P. bivia and
G. vaginalis in the range of killing
stipulated for the bactericidal activity of antimicrobial activity (>2
log-unit). In a previous study, Atassi et al. demonstrated that the
bactericidal activity of
Lactobacilli toward these two vaginal bacterial pathogens was strain dependent and occurred
within the first hours of coculture [
14]. In our experiments, a longer incubation time was required to observe
bactericidal activity, probably because of the different experimental
parameters used in the two assays. We previously showed that the Lcr35
probiotic strain was also able to kill several pathogens [
10]. The mechanism(s) underlying this activity has not been elucidated but
is likely to be multifaceted and probably includes the production of hydrogen
peroxide, lactic acid, and antibacterial compounds. It has been recently shown
that
G. vaginalis organized in
biofilms is more
resistant to H
2O
2 and lactic acid than planktonic
cultures [
17].
G. vaginalis is the
predominant species observed within biofilms present on the vaginal epithelium
in bacterial vaginosis [
18], and Saunders et al. recently showed that strains of
Lactobacilli were able to disrupt
G. vaginalis preformed biofilms [
13]. It would therefore be interesting to test the biofilm activity of
Lcr35 against
G. vaginalis and to
determine if the sessile form of Lcr35 also exhibits antibacterial activity
against
G. vaginalis in mixed biofilm
assays.
The antagonist activity of Lcr35 was not limited to
bacterial pathogens since the strain was also able to reduce the viability of
C. albicans. Several strains of
Lactobacilli have shown inhibitory
effects against
C. albicans [
16], which is the species most often associated with candidiasis. By
interfering with
Candida overgrowth
in the patients' intestinal or vaginal tract,
Lactobacilli could provide colonization resistance and maintain low
numbers of yeasts, especially when administered together with antibiotics.
Relevant clinical trials have suggested that
intravaginal or oral administration of
Lactobacillus strains is able to
increase the numbers of vaginal
Lactobacilli and restore the vaginal microbiota to normal [
7]. Lcr35 was isolated from a human intestinal and not vaginal microbiota
and does not belong to the four main species of
Lactobacilli considered to be predominantly linked to the vaginal
microflora,
L. crispatus,
L. jensenii,
L. gasseri, and
L. iners [
4,
19,
20], but it has been shown to survive within the human gastrointestinal
tract [
9]. Furthermore, Petricevic and Witt recently showed in a clinical study
that topical administration of Lcr35 enhances the restoration of the vaginal
flora after antibiotic treatment of BV [
21].
Thus, it might be an excellent candidate for use as a prophylactic
agent, taken orally or applied topically. In vivo studies to evaluate its
feasibility as such are in progress.
This article has been 
