Download Biofilms role in chronic infections.

Chad Blankenship
Advisor Dr. Bill Grimes
Clinical Health Sciences
Department
University of Kentucky
•A biofilm is a community of microorganisms
that usually consist of multiple species of
bacteria that have the ability to cause chronic
pathogenic infections in Humans.
Biofilm formation is a crucial step in the
pathogenesis of many chronic bacterial
infections, including foreign body related
infections (Infections on medical devices).
Biofilms are very difficult to eradicate with
conventional antimicrobial agents so they
create huge problems for practitioners in
forming treatment modalities that work .
Bacterial biofilms have several potential
antimicrobial resistance mechanisms.

Biofilms form when bacteria adhere to nutrient
surfaces in moist environments and begin to
excrete a slime layer that can anchor them to all
kinds of material – such as metals, plastics,
biomedical implants , and human tissue.
•Contact lenses
•Central venous catheters
•Endotracheal tubes
•Intrauterine devices
•Mechanical heart valves
•Pacemakers
•Dialysis catheters
•Urinary catheters
•Voice protheses


Nutrient acquisition
Protection
•Restricted
Penetration
•Decreased growth
rate
•Expression of
resistance genes

I just can't go with the
flow anymore. I've been
thinking about joining a
biofilm.
•Persister cells

http://www.erc.montana.edu/Res-Lib99SW/Movies/2005/05-M005.htm
•Plaque
•Infectious Bacterial Endocarditis
•Urinary tract infections
•Cystic Fibrosis
•Tuberculosis
•MRSA

Tuberculosis is a very relevant very contagious
pulmonary disease that is spread by direct
contact with respiratory droplets. It is
estimated that 1.6 million deaths resulted from
TB in 2005
•
Researchers have discovered that mycobacteria,
the etiologic agent of tuberculosis, has the ability
to form biofilms (Howard Hughes 2005). The
ability to form biofilms as discussed allows these
infections to persist causing chronic infections that
are not easily cured. It has been found however
that when mycobacterium species related to TB
pathogens lack one key protein, mature biofilms
fail to form. Corrupting this protein inactivates a
key gene (GroEL1) which prevents biofilm
formation and takes away the ability of the
bacteria to evade antimicrobial penetration
(Howard Hughes 2005). GroEL1 apparently
oversees the production of fatty acids called
mycolic acids that help in the production of mature
biofilms.

So, If we take away the biofilms ability to
protect the bacterial community we can then
use the traditional treatments in order to clear
these infections.

One in 3,000 Caucasian infants is afflicted with
this disorder, making Cystic Fibrosis one of the
most common genetic diseases, resulting in
lethality, in Caucasians. This means there are
approximately 30,000 Americans with CF, and
an estimated 8 million people who are
heterozygous for the defective gene that causes
the disease.
•
Cystic Fibrosis is caused by infection of the alveoli
of the lungs with Pseudomonas aeruginosa. The
alveoli slowly fill with mucous and damage is
caused to the lung tissue which cause labored
breathing and eventually death. Cystic Fibrosis is
now believed to form biofilms in the alveoli from
neutrophils. The infection is continually
challenged by the immune system with an endless
supply of neutrophils. The neutrophils themselves
increase the amount of debris that clog the alveoli
of the lungs. Scientists have found that the DNA
and a filament by the name of actin, develop the
structure the Pseudomonads need to from mature
biofilms. In the presence of these neutophils,
Pseudomonas is three times more likely to form
biofilms than if neutrophils were not present.
These biofilms give the pseudomonas increased
protection from assault by macrophages or
neutrophils that may try to penetrate the infection.


Periodontitis is an infection of the soft tissue
surrounding the teeth which is set into motion
by the substance known as plaque. Plaque is
the combination of bacteria and food
particulate mixed with salivary secretions. It is
widely known that plaque is an active biofilm.
Plague can advance to calculus which is tarter
found on the teeth.

More than one in three people over age 30 have
Periodontitis. And, by a conservative estimate,
35.7 million people in the United States have
Periodontitis (Albandar 1999).
•
is the inflammation of the endocardium or
inner layer of the heart. The most common
structures that become involved in this
inflammation are the four heart valves
themselves. In a paper by Braunwald he
suggests that the percentages of bacterial
infection for all popularly used prosthetic heart
valve remain in the same range of .5% - 4%.
However when these heart valves begin to leak
they form biofilms easily. The biofilms can
break away and get clogged in capillary beds
causing embolisms.
•
In the past few years the amount of MRSA
infections has gone up considerably. A 2007 report
in Emerging Infectious Diseases, (CDC), estimated
the number of MRSA infections doubled
nationwide, from approximately 127,000 in 1999 to
278,000 in 2005, while deaths increased from 11,000
to 17,000. JAMA estimated that MRSA was
responsible for 94,360 serious infections and
associated with 18,650 hospital deaths in the
United States in 2005. If the estimations are fair,
reports Rob Stein of the Washington Post, then
MRSA is responsible for more deaths each year
than AIDS.
•
In a study by F. Fitzpatrick et al in 2005 it was
found that isolates of MRSA contained the ica
operon that makes it possible for them to form
biofilms while isolates of MSSA (multi-strain
susceptible staphylococcus aureus) did not
contain the ica operon and are as the name
suggested more susceptible to antimicrobial
penetration. This research suggests that biofilm
formation is a important catalyst for resistance
in MRSA. Methicillin resistance coupled with
the ability to form biofilms is bad news for
future treatment efforts. The more we
understand about biofilm formation the more
likely we are to find a treatment.


There are not many answers about how to treat
chronic infections caused by biofilm
formation!!!
However, this is something that researchers
predict will trickle down into the medical field
in yrs to come.