Mechanism of mixed vaginitis
Polymicrobial
infections generally involve the formation of
mixed biofilms, dominated by
bacteria
and/or fungi, embedded in an
extracellular
matrix(14).
It
is even common to find mixed biofilms in
the lower female reproductive tract
in the clinical setting.
The
specific characteristics of mixed biofilms, especially their
enhanced drug resistance and their
ability to evade components of the host immune response, make them of
high clinical importance.
However,
despite the importance of such mixed infections, mixed infection
research, particularly research involving vastly diverse
microorganism, is in its infancy(15). Bacteria
and/or fungi can coexist within a host, and the nature of interspecies
interactions can determine the fate of the microbial populations.
They influence each other in
diverse ways via synergistic or
antagonistic interactions(16).
1. Medically
antagonistic
interactions between microorganism are common in
the lower female reproductive tract. For example, studies on the vaginal
microbiota have revealed that Lactobacillus species lower the local pH
(by releasing lactic acid), which results in the inhibition of initial
adherence of Candida albicans and Gardnerella vaginalis to
the vaginal mucosal surface(17).
Many
environmental cues impact biofilm formation, such as hypoxia, elevated
extracellular pH, body temperature, and elevated
CO2(18). A previous study reported thatPseudomonas
aeruginosa killed C. albicans cells after attachment to C.
albicans hyphae(19).
The
contemporaneous process may be dependent on the species present. Little
is known about pathophysiological vaginal conditions during infection,
but antagonistic interactions between probiotics
and pathogens are more
likely
to occur than antagonistic
interactions between pathogens.
2. Some synergistic
relationships result in complex pathogenic
processes, providing protection to one or both species in mixed-species
biofilms. This occurs
in
the following ways: ⑴
Cells
of certain species can directly bind to cells of other species. For
example, recent evidence has indicated thatStaphylococcus
aureus can “piggyback” on C. albicans hyphae to penetrate host
cells, infiltrate deep tissues and participate in the pathogenic process
of host cells(20). ⑵ Similar
synergies providing a protective microenvironment have also been
observed; for example, the presence of a C. albicans biofilm
enables the proliferation of anaerobic pathogens in an otherwise
hostile, oxygen-rich environment. Moreover, the bacteria seem to induce
the formation of these protective structures(21). ⑶
A recent study has linked this
protective interaction to enhanced drug resistance; when C.
albicans and methicillin-resistant Staphylococcus aureus (MRSA)
strains were grown together, the presence of C. albicans seemed
to protect MRSA from eradication by
vancomycin(22).
⑷
Synergistic interactions can also
enhance virulence during infection(19).
For example, higher host mortality
was observed when S. aureus and C. albicans were
introduced together at sublethal doses in a mouse peritonitis infection
model than when either species was introduced
alone(23).
A
limitation of these studies was that this interaction was evaluated not
in the lower female reproductive tract.
However, these observations
illustrate the dynamic nature of polymicrobial infections in part.
In other words,
the
contemporaneous process may be interdependent.
The
mechanisms behind these synergistic
interactions have not been
described.
3. We have focused on
antagonistic versus synergistic interactions, but additional distinct
interactions exist. Polymicrobial
infections challenge the immune system in different ways compared with
infection with a single
organism.
An
host response to one pathogen may promote the proliferation of another
pathogen. For example, coinfection
withStreptococcus agalactiaesignificantly attenuated the hyphal development of C. albicans in
vitro,
but
it may attenuate host vaginal
mucosal TH17 immunity and contribute to mucosal colonization by C.
albicans in vivo(24). A
multicountry cross-sectional study reported that the factor
independently associated with S. agalactiae was C.
albicans presence(25). Similarly, another study suggested that C.
albicans may suppress the local host immune response, allowing
subclinical P. aeruginosa to proliferate, resulting in
disease(26)
(Figure
1). Thus, these interactions are
highly complex, and the type of interaction that occurs often depends on
a range of environmental,
pathogenic and host factors. The
mechanisms of mixed infections in vaginitis are unknown thus far, and
further exploration is needed.