Mucus covers the moist surfaces of the human body,
including the eyes, nostrils, lungs, and gastrointestinal tract. In fact, the
average person makes more than a liter of mucus each day! It houses trillions
of microbes and serves as a first line of defense against the subset of those
microorganisms that cause infections. For these reasons, NIH-funded
researchers, led by Katharina Ribbeck, Massachusetts Institute of Technology,
Cambridge, are out to gain a greater understanding of the biology of healthy mucus—and
then possibly use that knowledge to develop new therapeutics.
The author concluded:
The researchers found that in the presence of glycans, P.
aeruginosa was rendered less harmful and infectious. The bacteria also produced
fewer toxins. The findings show that it isn’t just that microbes get trapped in
a tangled web within mucus, but rather that glycans have a special ability to
moderate the bugs’ behavior. The researchers also have evidence of similar
interactions between mucus and other microorganisms, such as those responsible
for yeast infections. The new study highlights an intriguing strategy to tame,
rather than kill, bacteria to manage infections. In fact, Ribbeck views mucus
and its glycans as a therapeutic gold mine. She hopes to apply what she’s
learned to develop artificial mucus as an anti-microbial therapeutic for use
inside and outside the body. Not bad for a substance that you might have
thought was nothing more than slimy stuff.
One of the referred authors has noted:
A slimy, hydrated mucus gel lines all wet epithelia in
the human body, including the eyes, lungs, and gastrointestinal and urogenital
tracts. Mucus forms the first line of defence while housing trillions of
microorganisms that constitute the microbiota1. Rarely do these microorganisms
cause infections in healthy mucus1, suggesting that mechanisms exist in the
mucus layer that regulate virulence. Using the bacterium Pseudomonas aeruginosa
and a three-dimensional (3D) laboratory model of native mucus, we determined
that exposure to mucus triggers downregulation of virulence genes that are
involved in quorum sensing, siderophore biosynthesis and toxin secretion, and
rapidly disintegrates biofilms—a hallmark of mucosal infections. This
phenotypic switch is triggered by mucins, which are polymers that are densely
grafted with O-linked glycans that form the 3D scaffold inside mucus. Here, we
show that isolated mucins act at various scales, suppressing distinct virulence
pathways, promoting a planktonic lifestyle, reducing cytotoxicity to human
epithelia in vitro and attenuating infection in a porcine burn model. Other
viscous polymer solutions lack the same effect, indicating that the regulatory
function of mucin does not result from its polymeric structure alone. We
identify that interactions with P. aeruginosa are mediated by mucin-associated
glycans (mucin glycans). By isolating glycans from the mucin backbone, we
assessed the collective activity of hundreds of complex structures in solution.
Similar to their grafted counterparts, free mucin glycans potently regulate
bacterial phenotypes even at relatively low concentrations. This regulatory
function is likely dependent on glycan complexity, as monosaccharides do not
attenuate virulence. Thus, mucin glycans are potent host signals that ‘tame’
microorganisms, rendering them less harmful to the host.
This has been generally thought to be the case but this
closer examination opens doors to understanding perhaps how to use mucus as a
therapeutic and/or preventive agent.
A second referred to article by Co et al notes:
Mucus is a biological gel that lines all wet epithelia in
the body, including the mouth, lungs, and digestive tract, and has evolved to
protect the body from pathogenic infection. However, microbial pathogenesis is
often studied in mucus-free environments that lack the geometric constraints
and microbial interactions in physiological three-dimensional mucus gels. We
developed fluid-flow and static test systems based on purified mucin polymers,
the major gel-forming constituents of the mucus barrier, to understand how the
mucus barrier influences bacterial virulence, particularly the integrity of
Pseudomonas aeruginosa biofilms, which can become resistant to immune clearance
and antimicrobial agents. We found that mucins separate the cells in P.
aeruginosa biofilms and disperse them into suspension. Other viscous polymer
solutions did not match the biofilm disruption caused by mucins, suggesting
that mucin-specific properties mediate the phenomenon. Cellular dispersion
depended on functional flagella, indicating a role for swimming motility. Taken
together, our observations support a model in which host mucins are key players
in the regulation of microbial virulence. These mucins should be considered in
studies of mucosal pathogenesis and during the development of novel strategies
to treat biofilms.
This appears to have been a further proof of the
observations.
Biofilms often can get established on various bodily
surfaces. As noted in McGarty (2016):
Biofilms present a challenge to any system which
processes and distributes fluids across uncontrolled environments. This is
particularly the case in the deployment and operations of public drinking water
systems. The biofilm is the result of the colonization and extension of
micro-organisms which adhere to the surfaces and in turn create a colony of
more micro-organisms and the agglomeration of microbiological products in an
extracellular matrix producing and ever increasing colony of microorganisms
which result in impairments to the flow of the water and putatively could
result in significant contamination of the water as well. In this paper we examine
the issue of the creation and sustaining of biofilms as a function of surface
roughness. It has been demonstrated that the application of nano Se or the
application of lipase to create and equivalent nano roughness can act as a
bacteriostatic environment and deter the growth of bacteria. The explanation of
this phenomena has been presented in a multiplicity of ways all having
substantial difficulties. At one extreme one uses the concept of surface energy
in terms of Gibbs free energy. This assume a large scale phenomenon and fails
to adequately account for the detailed physics of adhesion. At the other
extreme we have the DLVO model which includes a combination of van der Waals
forces along with dual barrier forces creating double energy catching levels,
one for reversible and one irreversible. However, it appears that all such
models are deficient. We examine these models, and make some observations that
may assist in a process leading to some clarity. We also present this in the
context of biofilm control for potable water systems, a significant problem.
Thus, biofilms seem to be inhibited by mucins, and the
benefit may be extensive. The next issue is what initiates mucus? As Hopkins
has noted:
Chronic rhinosinusitis includes a heterogeneous group of
conditions with differing pathophysiologies. Two main subgroups are described:
with and without nasal polyps. Chronic rhinosinusitis without nasal polyps may
be idiopathic or odontogenic or may be caused by immunodeficiency, vasculitis,
or other autoimmune conditions. The majority of cases of chronic rhinosinusitis
with nasal polyps are idiopathic but may also occur as part of genetic,
metabolic, or immunologic diseases. The majority of white patients with chronic
rhinosinusitis with nasal polyps have a type 2 pattern of inflammation,
characterized by eosinophilia and elevated levels of interleukin-4,
interleukin-5, and interleukin-13 cytokines. This finding may not apply to
other racial groups, but further study is required.
Thus mucus in the nasal sinuses, a major site of such, protective
of many infections, may be over-activated by polyps, which in a sense are
neoplasia in the cavity, as well as by other irritations such as dental changes
irritating the basal cilia of the sinus, a mechanical or even thermal irritant
and the response thereto.
It is interesting to examine this common phenomenon as a
disease inhibitor and preventive.
References
1. Co et al, Mucins trigger dispersal of Pseudomonas aeruginosa
biofilms, npj Biofilms Microbiomes 4, 23 (2018)
2. Hopkins, Chronic Rhinosinusitis with Nasal Polyps, NEJM, V 381,
July 4, 2019
3. Lai et al, Micro- and macrorheology of mucus, Adv Drug Deliv
Rev. 2009 February 27; 61(2): 86–100
4. McGarty, Biofilm Growth and Infiltration, https://www.researchgate.net/publication/301803414_Biofilm_Growth_and_Infiltration
5. Shale and Ionescu, Mucus hypersecretion: a common symptom, a
common mechanism?, Eur Respir J 2004, 23, 797-798
6. Wheeler et al, Mucin glycans attenuate the virulence of
Pseudomonas aeruginosa in infection, Nature Microbiology volume 4, pages2146–2154,
2019
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