biology

+
medicine

Bacterial Pathogenesis:
Friend or Foe?
A STANFORD PROFESSOR STUDIES THE
BENEFITS OF BACTERIAL INFECTION
by Chelsea Young and Nisha Gadgil

I
t may be scary to think that our bodies are home to ten times at Stanford were the first to isolate and characterize the
more tttttv cells than our own cells. However, in a recent genes associated with pathogenic susceptibility.
article published in the journal Cell, “Is Persistent Bacterial Falkow’s most recent publication represents a
Infection Good for Your Health?” Dr. Stanley Falkow, culmination of years of research exploring how the bacteria
professor of Microbiology and Immunology at Stanford, suggests Salmonella and Helicobacter pylori bring about a broad
that the “sea of microbes” living in both our external environment range of symptoms within a host. He has discovered that
and inside our bodies is an integral part of our natural flora. some pathogenic bacteria may actually have a beneficial
side to those they infect.

Pioneering Bacteria Research Genetic Differences in Salmonella Resistance
Throughout his career, Falkow has transformed the way in Salmonella invades specialized epithelial cells of the
which we study bacterial pathogens by focusing on the biochemical intestinal tract to access underlying lymphatic tissue
factors that lead that disseminate the bacteria throughout the body.
to persistent
infection and the “I’ve never met a
ways that bacteria
manipulate the bacterium I didn’t like.”
host genome.
He has worked Although initial contact with the bacteria may result in
with bacteria that acute infection, long term infection is usually innocuous.
Photo credit: http://www.niaid.nih.gov/dir/labs/images/LHPBfrontimage.jpg

cause ailments Salmonella can live in the immune system’s white blood
as diverse as cells for a host’s entire life without ever causing clinical
whooping cough, symptoms of infection.

Several common pathogens infect host cells.

gonorrhea, meningitis, typhoid, dysentery, urinary tract infections, The team looked at all genes expressed in white
and travelers’ diarrhea. Falkow and his team were the first to apply blood cells from an asymptomatic host that was
the methods of recombinant DNA and genetic engineering to the chronically infected with Salmonella. The study
field of bacterial pathogenesis, and under Falkow’s guidance, labs revealed clusters of genes that were modified from their

12 stanford scientific
 biology
+
medicine

As the prevalence of H. pylori, and

subsequently ulcers and gastric cancer,
has decreased over the years due to
antibiotic use, the incidence of esophageal
cancer has increased dramatically. This
http://www3.niaid.nih.gov/NR/rdonlyres/602F2642-A309-4D88-B408-604FD507B38B/0/SALMON_1.JPG

trend is observed among many different

bacteria as well: bacterial diseases
including tuberculosis, measles, mumps
and whooping cough are becoming less
prevalent while diseases such as asthma,
allergies, and certain kinds of diabetes
are simultaneously on the rise.
Epidemiological evidence suggests
that H. pylori actually has a protective
effect against esophageal cancer.
Additionally, epidemiological evidence
as well as animal models show that
there is an inverse relationship between
the incidence of infectious diseases and
the incidence of immune disorders. In
other words, the more microbe-free our
environment, the more likely we may be
to fall victim to allergies and autoimmune
diseases.
Although the main focus of
pathogenesis has always been on the
Salmonella bacteria invade cultured human cells adverse effects of disease, Falkow asserts
that more often than not, both parties
normal patterns of gene expression. Specifically, expression actually benefit from the host-pathogen interaction. “In the
of the gene Nramp1 in mice was found to control intracellular process of immunizing, we stop the organism from being able to
replication of Salmonella. This means that genetic differences grow,” he explains. “I have no idea if it’s going to be bad, going to
between individuals, such as their different levels of Nramp1 be good, or doesn’t matter.”
expression, may result in different susceptibilities to infection. As a result, the line between pathogens and commensals-
-organisms that interact with their hosts without negatively
H. pylori in Most of Us affecting them--is often ambiguous and subtle. Falkow has been
Falkow’s research on H. pylori, a bacterium that causes puzzled by this for many years. Although he defines pathogens by
symptoms ranging from gastritis to ulcers and stomach cancer, “their inherent ability to cross anatomical barriers, inhabit tissue
reveals that ninety percent or more of humans are infected with H. sites, or breach host defenses,” this definition is complicated by
pylori. As a result, they display mild inflammation of the stomach the notion that even these invasive pathogens seem to have some
lining. Only one percent of these individuals ever develop ulcers beneficial effects. While definitive proof has yet to be found,
or gastric cancer. While treatment of H. pylori with antibiotics Falkow warns that scientists should be wary of the negative side
is generally successful, re-infection is rapid and severe due to effects of killing off our tiny bacterial friends. S
residually infected quiescent cells that the host is unable to destroy.
Nisha Gadgil is a freshman majoring in Chemical Engineering. In her free
The more microbe-free our time she enjoys tennis, running, and spending time with friends.
environment, the more likely we Chelsea Young, also a freshman, is double majoring in Biological Sciences
and Communications. She likes meeting new people, running, and
may be to fall victim to allergies sleeping.
and autoimmune diseases.
To Learn More:
Pathogenic Bacteria are Good for You? Departmental website of Dr. Stanley Falkow:
Studying Salmonella, H. pylori, and other pathogenic bacteria http://med.stanford.edu/profiles/Stanley_Falkow/
from the standpoint that bacteria are present in all of us but rarely
bring about chronic disease, Falkow formed an unconventional Falkow, Stanley. “Is Persistent Bacterial Infection Good for Your
idea that pathogenic bacteria may even carry some health benefits. Health?” Cell 124 (Feb. 2006): 699-702.

layout design:Ly Nguyen volume iv 13