Bacterial Pa Tho Genesis -- Friend Or Foe

biology + medicine

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

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t may be scary to think that our bodies are home to ten times more tttttv cells than our own cells. However, in a recent article published in the journal Cell, “Is Persistent Bacterial Infection Good for Your Health?” Dr. Stanley Falkow, professor of Microbiology and Immunology at Stanford, suggests that the “sea of microbes” living in both our external environment and inside our bodies is an integral part of our natural flora.

Pioneering Bacteria Research

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Throughout his career, Falkow has transformed the way in which we study bacterial pathogens by focusing on the biochemical factors that lead to persistent infection and the ways that bacteria manipulate the host genome. He has worked with bacteria that cause ailments as diverse as whooping cough,

at Stanford were the first to isolate and characterize the genes associated with pathogenic susceptibility. Falkow’s most recent publication represents a culmination of years of research exploring how the bacteria Salmonella and Helicobacter pylori bring about a broad range of symptoms within a host. He has discovered that some pathogenic bacteria may actually have a beneficial side to those they infect.

Genetic Differences in Salmonella Resistance Salmonella invades specialized epithelial cells of the intestinal tract to access underlying lymphatic tissue that disseminate the bacteria throughout the body.

“I’ve never met a bacterium I didn’t like.” Although initial contact with the bacteria may result in acute infection, long term infection is usually innocuous. Salmonella can live in the immune system’s white blood cells for a host’s entire life without ever causing clinical symptoms of infection.

Several common pathogens infect host cells.

gonorrhea, meningitis, typhoid, dysentery, urinary tract infections, and travelers’ diarrhea. Falkow and his team were the first to apply the methods of recombinant DNA and genetic engineering to the field of bacterial pathogenesis, and under Falkow’s guidance, labs

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The team looked at all genes expressed in white blood cells from an asymptomatic host that was chronically infected with Salmonella. The study revealed clusters of genes that were modified from their

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biology + medicine

Salmonella bacteria invade cultured human cells

normal patterns of gene expression. Specifically, expression of the gene Nramp1 in mice was found to control intracellular replication of Salmonella. This means that genetic differences between individuals, such as their different levels of Nramp1 expression, may result in different susceptibilities to infection.

H. pylori in Most of Us Falkow’s research on H. pylori, a bacterium that causes symptoms ranging from gastritis to ulcers and stomach cancer, reveals that ninety percent or more of humans are infected with H. pylori. As a result, they display mild inflammation of the stomach lining. Only one percent of these individuals ever develop ulcers or gastric cancer. While treatment of H. pylori with antibiotics is generally successful, re-infection is rapid and severe due to residually infected quiescent cells that the host is unable to destroy.

The more microbe-free our environment, the more likely we may be to fall victim to allergies and autoimmune diseases. Pathogenic Bacteria are Good for You? Studying Salmonella, H. pylori, and other pathogenic bacteria from the standpoint that bacteria are present in all of us but rarely bring about chronic disease, Falkow formed an unconventional idea that pathogenic bacteria may even carry some health benefits.

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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 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 adverse effects of disease, Falkow asserts that more often than not, both parties actually benefit from the host-pathogen interaction. “In the process of immunizing, we stop the organism from being able to grow,” he explains. “I have no idea if it’s going to be bad, going to be good, or doesn’t matter.” As a result, the line between pathogens and commensals-organisms that interact with their hosts without negatively affecting them--is often ambiguous and subtle. Falkow has been puzzled by this for many years. Although he defines pathogens by “their inherent ability to cross anatomical barriers, inhabit tissue sites, or breach host defenses,” this definition is complicated by the notion that even these invasive pathogens seem to have some beneficial effects. While definitive proof has yet to be found, Falkow warns that scientists should be wary of the negative side effects of killing off our tiny bacterial friends. S Nisha Gadgil is a freshman majoring in Chemical Engineering. In her free time she enjoys tennis, running, and spending time with friends. Chelsea Young, also a freshman, is double majoring in Biological Sciences and Communications. She likes meeting new people, running, and sleeping. To Learn More: Departmental website of Dr. Stanley Falkow: http://med.stanford.edu/profiles/Stanley_Falkow/ Falkow, Stanley. “Is Persistent Bacterial Infection Good for Your Health?” Cell 124 (Feb. 2006): 699-702.

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