The primary colonizing bacteria of a healthy individual are of the

genus Lactobacillus.[2] Since the first description of lactobacilli by

Dderlein, lactobacilli have been generally considered as the
gatekeepers of the vaginal ecosystem. Lactobacilli have been
shown to inhibit in vitro growth of pathogenic microorganisms,
e.g. Bacteroides fragilis, Escherichia coli, Gardnerella
vaginalis, Mobiluncus spp., Neisseria
gonorrhoeae, Peptostreptococcus anaerobius, P.
bivia and Staphylococcus aureus. It is generally accepted that this
is achieved mainly through the action of lactic acid.[4][5][6][7] Moreover,
lactobacilli normally help to prevent long-term colonization of the
vagina by adhering to vaginal epithelial cells. This usually reduces
pathogens from infecting to the vaginal epithelium.[8]
Next to lactic acid production and competition for adherence, other
antagonistic mechanisms include hydrogen peroxide (a broad-
spectrum antimicrobial) and bacteriocins (target-specific
antimicrobials) production.[9][10]
The production of lactic acid[edit]
Low pH is generally accepted to be the main mechanism controlling
the composition of the vaginal microflora. Although the lactic acid
produced by lactobacilli contributes to the vaginal acidity, it is still
not proven to be the primary source of low vaginal pH, but the fact
remains that most lactobacilli thrive best at a pH < 4.5 .[11][12][13]
Hydrogen peroxide[edit]
Production of hydrogen peroxide (H2O2) is a well-known mechanism
for bacterial antagonism,[14][15][16] inhibiting growth of microorganisms
via direct interaction or via human
myeloperoxidase.[17][18][19] Hydrogen peroxide-producing lactobacilli
have been shown to inactivate HIV-1, herpes simplex virus type 2
(HSV-2), Trichomonas vaginalis, G. vaginalis, P. bivia and E.
coli.[10][20] found that 96% of Lactobacillus species from a healthy
vaginal ecosystem produced H2O2 (L. jensenii and L.
vaginalis produce the highest levels of H2O2,[9][21] whereas only 6% of
the lactobacilli recovered from women with BV produced H2O2.[17] In
agreement with this, L. iners, most frequently associated with
disturbed vaginal microflora,[22][23] is a poor producer of
H2O2.[24][25] Vaginal colonization by H2O2-producing lactobacilli has
been associated with a decrease in the occurrence of bacterial
vaginosis (BV).[26] However, more recently OHanlon et
al.[27] demonstrated that cervicovaginal fluid and semen have a
significant H2O2-blocking activity and they later [10] demonstrated that
physiological concentrations of H2O2 below 100 M fail to inactivate
any of the 17 tested BV-associated bacteria, e.g. A. vaginae, G.
vaginalis, Mobiluncus spp., P. bivia, Prevotella
corporis, Mycoplasma hominis, even in the presence of human
myeloperoxidase, known to increase the microbicidal activity of
H2O2.[10] Only supraphysiologic concentrations of exogenous
H2O2 (0.34% w/v, 100 mM) were sufficient to inactivate BV-
associated bacteria at which concentration it more potently
inactivated vaginal lactobacilli (L. crispatus, L. gasseri, L.
iners and L. jensenii). A concentration of 100 mM H2O2 is
approximately 50-fold higher than lactobacilli are capable of
producing even under optimal aerobic, low-antioxidant conditions,
and approximately 5,000-fold higher than the estimated
H2O2 concentration in vivo. Even more remarkable, the addition of
only 1% vaginal fluid blocked the microbicidal activity of 1 M H2O2.
Possible explanations may be that cervicovaginal fluid and semen
contain proteins, glycoproteins, polysaccharides, lipids, and other
molecules with the potential to react with and inactivate H2O2. In
addition, the vagina is hypoxic most of the time, whereas lactobacilli
require oxygen to produce hydrogen peroxide. It is also remarkable
that catalase, which provides bacteria protection against toxic H2O2,
is absent in lactobacilli,[17][28] and as such they would be unprotected
against their own H2O2 production. In contrast, under optimal
anaerobic growth conditions, physiological concentrations of lactic
acid inactivated the BV-associated pathogens without affecting the
vaginal lactobacilli.[10][27] In summary, although the hydrogen
peroxide production of lactobacilli has been considered as an
important antimicrobial component, contributing to the colonization
resistance provided by lactobacilli,[9][29] and although there seems to
be a link between H2O2-producing lactobacilli and normal vaginal
microflora, recent data do not support this role for H2O2.[10][27]
Bacteriocins[edit]
Vaginal lactobacilli produce antimicrobial peptides, i.e. bacteriocins
such as lactocin 160 and crispasin.[11] with inhibitory activity ranging
from narrow (closely related Lactobacillus species) to broad
(diverse groups of bacteria, including G. vaginalis and P.
bivia),[6] and bacteriocin-like substances, with a broader spectrum of
activity than bacteriocins (e.g. a heat-resistant peptide produced
by Lactobacillus salivarius subsp. salivarius CRL 1328). Several
studies have indicated that the activity of bacteriocins is favored by
low pH.
The inhibitory substances produced by vaginal Lactobacillus is a
primary factor in protecting the vaginal microbiota, with organic
acids, bacteriocins, and hydrogen peroxide. These act
synergistically against infection by pathogens. Not
all Lactobacillus spp. and not all strains within
one Lactobacillus species exhibit all 3
mechanisms.[11] Lactobacillus species differ in premenopausal
women, i.e. L. crispatus, L. jensenii, L. iners, L. gasseri (and
possibly L. vaginalis), as assessed through cultivation-dependent
and cultivation-independent techniques.[22][23][24][30] Vaginal lactobacilli
have been shown to display a pronounced vaginotropism, and their
pili act as ligands for attachment to receptors of vaginal epithelial
cells. The limited number of Lactobacillus spp. found in the human
vagina is remarkable, which leads to the possibility that there are
host factors that select for specific organisms, that these species
have unusual characteristics that allow them to successfully
colonize the vagina, or both .[31] However, the vaginotropism, does
not only apply to this selected group of lactobacilli that stand for a
healthy vagina, but also for the bacterial species associated with
BV.[32] The microbiota detected in the human genital and gut
econiche do not appear to grow outside their host and probably are
likely to rely on the close contact between parents and their children
for transmission,[32] e.g. mother to neonate transmission of genital
microflora, most probably also with gut microflora homogenously
distributed over the babys body including skin, the oral cavity,
nasopharynx, and feces.[33]

Other microbiota[edit]
The normal vaginal microbiota that is dominated by lactobacilli can
differ among some ethnic groups. Non-pathogenic vaginal species
are part of the normal microbiota of some women.[22][34] Several
studies have demonstrated that a significant proportion (733%) of
healthy asymptomatic women (especially black and Hispanic
women)[35] lack appreciable numbers of Lactobacillus species in the
vagina,[31][36] and instead have a vaginal microbiota that consist of
other lactic acid-producing bacteria, i.e. species from the
genera Atopobium, Leptotrichia, Leuconostoc, Megasphaera, Pedio
coccus, Streptococcus and Weissella,[30][31][35] All ethnic populations
have vaginal microflora communities containing lactic acid
producing bacteria.[31][31][35] This implies that not all communities may
be equally resilient, so that if the resilience of a vaginal community
is low then transitory changes in the structure of these communities
may occur more readily in response to disturbances of various
kinds, including menses, sexual intercourse, douching and
contraceptive practices. These differences in the structure and
composition of microbial communities may underlie well-known
differences in the susceptibility of women in these racial groups to
BV and various vaginal infections.[35][37][38]Although it can be agreed
that we should be cautious about which vaginal microflora should
be considered as disturbed, and although (lactic) acid is indeed
produced by many species in each of these communities, the
remark by Mirmonsef et al.[39] that emphasis should be on vaginal
pH and not on mere acid production in establishing normal vaginal
microbiota may be justified. The pH further decreases during
pregnancy.[40]

Other vaginal bacterial species[edit]

Further information: List of bacterial vaginosis microbiota
Other bacterial species are frequently found in the vagina, such as
the Gram positive cocci: Atopobium
vaginae, Peptostreptococcus spp., Staphylococcus spp., Streptococ
cus spp., and Bacteroides spp., Fusobacterium spp., Gardnerella
vaginalis, Mobiluncus, Prevotella spp., and Gram-negative enteric
organisms, such as Escherichia coli.[22][23] Mycoplasma and
Ureaplasma are frequently found in the vagina. Some of the
obligate and facultative anaerobic bacteria are associated with
BV.[36]
N.gonorrhea memiliki pili yang dapat memediasi perlekatan, dan memberi perlindungan dari
aliran urin di urethra serta sebagai pelindung terhadap fagositosis. N.gonorrhea memiliki
Lipooligosakarida (LOS) yang mampu menghambat fungsi silia di mukosa traktus genitalia.

N.gonorrhea mampu menghindari sistem imun manusia dengan cara variasi antigen oleh
protein Por dan komponen LOS. Variasi antigen ini juga berperan dalam infeksi berulang
dalam waktu yang singkat pada host yang sama. Bakteri ini juga memproduksi igA protease
yang menghambat sistem imun humoral.

Kerusakan pada jarigan mukosa traktus genitalia disebabkan oleh respon inflamasi dan
produksi sitokin-sitokin inflamasi terhadap bakteri.

Infeksi dapat menyebar secara retrograde, hal ini akan menyebabkan penyakit radang panggul
(Pelvic Inflammatory Disease), salpingitis, endometritis, dan/atau abses tubo-ovarian.
Penyebaran juga dapat menyebabkan peritonitis dan perihepatitis(Fitz-Hugh-Curtis
Syndrome)

*Pelvic Inflammatory Disease merupakan infeksi pada traktus genitalia bagian atas (Uterus,
Tubafalopi, Ovarium)

Infeksi sistemik dapat terjadi ketika sistem imun host menurun, terutama pada mereka yang
memiliki defisiensi komplemen tahap akhir (C6-C9). Gejala sistemik biasanya bermanifestasi
sebagai arthritis.

Neisseria gonorrhoeae dapat ditularkan melalui kontak seksual atau melalui penularan vertikal
pada saat melahirkan. Bakteri ini terutama mengenai epitel kolumnar dan epitel kuboidal
manusia. Patogenesis gonore terbagi menjadi 5 tahap sebagai berikut13:
Fase 1 adalah bakteri Neisseria gonorrhoeae menginfeksi permukaan selaput lendir dapat
ditemukan di uretra, endoserviks dan anus.
Fase 2 adalah bakteri ke microvillus sel epitel kolumnar untuk kolonisasi selama infeksi, bakteri
dibantu oleh fimbriae, pili.
Fimbriae terutama terdiri dari protein pilin oligomer yang digunakan untuk melekatkan bakteri ke
sel-sel dari permukaan selaput lendir. Protein membran luar PII 9
Oppacity associated protein (OPA) kemudian membantu bakteri mengikat dan menyerang sel
inang.
Fase 3 adalah masuknya bakteri ke dalam sel kolumnar dengan proses yang disebut endositosis di
mana bakteri yang ditelan oleh membran sel kolumnar, membentuk vakuola.
Fase 4 adalah vakuola ini kemudian dibawa ke membran basal sel inang, dimana bakteri
berkembang biak setelah dibebaskan ke dalam jaringan subepitel dengan proses eksositosis.
Peptidoglikan dan bakteri LOS (Lipo Oligo Sakharida) dilepaskan selama infeksi. Gonococcus
dapat memiliki dan mengubah banyak jenis antigen dari Neisseria LOS. LOS merangsang tumor
necrosis factor, atau TNF, yang akan mengakibatkan kerusakan sel.
Fase 5 reaksi inflamasi yang dihasilkan menyebabkan infiltrasi neutrofil. Selaput lendir hancur
mengakibatkan akumulasi Neisseria gonorrhoeae dan neutrofil pada jaringan ikat subepitel.
Respon imun host memicu Neisseria gonorrhoeae untuk menghasilkan protease IgA ekstraseluler
yang menyebabkan hilangnya aktivitas antibodi dan mempromosikan virulensi.

N. Neisseria gonorrhoeae, N. meningitidis, Haemophilus influenzae, Streptococcus pneumoniae

dan Streptococcus mutans, yang dapat tumbuh pada permukaan tubuh, memproduksi protease
IgA sekretori IgA yang tidak aktif dengan membelah molekul di daerah engsel, memisahkan
wilayah Fc imunoglobulin tersebut.

The lactobacillus species of bacteria appears to frequently colonize vaginal

mucosa (mostly the species gasseri, jensenii, iners, and crispatus[22][23]), of
which casei is present in some samples.[24] A vaginal state characterized by a
deficiency of lactobacillus bacteri (in general rather than a specific strain)
appears to be associated with increased risk for bacterial vaginosis[25] and may
promote the transmission of sexually transmitted infections (STIs) relative to a
sufficient state.[26][27][24]

Lactobacillus casei is one of the many species present in vaginal mucosa, but
the relevance of this information to oral supplementation of the bacteria is not
known
The concept of delivering lactobacilli orally to repopulate the vagina was first
reported in 2001 [76], and based upon the question if urogenital pathogens can do
this, why cannot lactobacilli? The organisms were delivered in a milk base and
shown to be recovered from the rectum [77]; therefore supporting the concept that
ingested strains could pass through the intestine, reach the rectum, and potentially
ascend to the vagina. This was confirmed independently by others