Cells that line the respitory tract normally exude a layer of tear-
like liquid using cystic fibroisis transmembrane conductance factor.
In some people who have Cystic Fibrosis have a version of this fluid
pump that does not work so well.

Bacteria such as Staph A. produce an enzyme that inhibits CTFR, which
leads to thick gooy mucus in patients who do not have any anomolies in
their cystic fibrosis transmembrane conductance factor, as well as
those who do.

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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra
ctPlus&list_uids=17400751&query_hl=4&itool=pubmed_docsum
Inhibition of CFTR Cl- channel function caused by enzymatic hydrolysis
of sphingomyelin.Ramu Y, Xu Y, Lu Z.
Department of Physiology, University of Pennsylvania, 3700 Hamilton
Walk, Philadelphia, PA 19104.

Numerous mutations in the cystic fibrosis (CF) transmembrane
conductance regulator (CFTR, a Cl(-) channel) disrupt salt and fluid
transport and lead to the formation of thick mucus in patients'
airways. Obstruction by mucus predisposes CF patients to chronic
infections and inflammation, which become gradually harder to control
and eventually fatal. Aggressive antibiotic therapy and supportive
measures have dramatically lengthened CF patients' lives. Here, we
report that sphingomyelinases (SMase) from human respiratory pathogens
strongly inhibit CFTR function. The hydrolysis of sphingomyelin by
SMase makes it more difficult to activate CFTR by phosphorylation of
its regulatory domain. By inhibiting CFTR currents, SMase-producing
respiratory tract bacteria may not only aggravate pulmonary infection
in some CF patients but may also elicit a condition, analogous to CFTR
deficiency, in non-CF patients suffering from bacterial lung
infection.

PMID: 17400751 [PubMed - in process]

==============================================================================

Cystic Fibrosis Treatment: New Study On Lung-infecting Bacterial
Enzyme Suggests New Approach

Science Daily - Researchers at the University of Pennsylvania School
of Medicine discovered that an enzyme produced by lung-infecting
bacteria further shuts down a protein that is defective in cystic
fibrosis patients. The disruption to this protein that conveys ions
from lung cells to airways causes thick mucus to buildup inside the
lung. The finding suggests a new therapeutic target for treating lung
infections in some cystic fibrosis (CF) patients.

Lung infection, facilitated by CF mutations, is the main cause of
death in CF patients. This bacterial component to CF now helps explain
why the severity of CF symptoms did not match the pathological effect
of the CF mutation alone. The study was published this month in the
Proceedings of the National Academy of Sciences.

The research, conducted by Zhe Lu, MD, PhD; Yajamana Ramu, PhD; and
Yanping Xu, MD, PhD, of the Department of Physiology, shows that the
bacterial enzyme, called sphingomyelinase (SMase), disables a protein
in lungs called CFTR, for cystic fibrosis transmembrane conductance
regulator. SMase is made by the bacteria that cause pneumonia, some
anthrax-causing bacteria, and bacteria that cause opportunistic
infections in CF and AIDS patients.

In healthy lungs, CFTR allows the passage of chloride ions (and
accompanying water) into airways, creating a thin layer of fluid to
keep airways clear. However, SMase, secreted by certain respiratory
tract bacteria, breaks down lipids surrounding CFTR and thereby
suppresses CFTR's chloride-passing function. To make matters worse,
the products of the lipid breakdown are also known to trigger
inflammation and cell death.

Together, these facts compellingly suggest that SMase plays a critical
role in the heretofore mysterious pathogenesis of lung injury in CF
patients. They also present a new paradigm for treating CF. Specific
inhibitors against the enzyme, in conjunction with current antibiotic
treatments and supportive measures, might be a viable near-term
approach to improving length and quality of life for many CF patients,
before CF gene therapy becomes a reality.

The Penn research team demonstrated the disruptive action of SMase in
frog oocytes (egg cells) engineered to place CFTR in their membrane.
These oocytes are an experimental tool that allows the researchers to
assess the flow of ions across the membrane by measuring electrical
current. The researchers found that direct exposure of the CFTR-
containing oocytes to SMase of Staphylococcus aureus and Bacillus
anthracis bacteria shuts off the electrical current passing through
not only the normal, but also the CF-causing mutant CFTR.

==
I think the sentance above was supposed to read,
"SMase of Staphylococcus aureus and Bacillus anthracis bacteria shuts
off the electrical current passing through not only the CF-causing
mutant CFTR, but also normal CFTR."
==
The next step for the research team is to develop specific inhibitors
against the bacterial SMase and test the idea in an animal model.

The National Institute of General Medical Sciences provided funding
for this research.

Note: This story has been adapted from a news release issued by
University of Pennsylvania School of Medicine.