Bacterial Pathogens Sense and Respond to Host Environments Karen Ottemann, Microbiology and Environmental Toxicology Karen Ottemann's laboratory investigates how bacteria translate chemical and physical cues in their host environment into adaptive responses. Mistakes in sensation and subsequent gene expression by bacteria may result in their elimination by the host immune response or peristaltic flow. Elucidation of such processes will hopefully lead to identification of anti-bacterial drug targets. Ottemann is particularly interested in the role of chemoreceptors and chemotaxis associated with the bacterium Helicobacter pylori. This pathogen infects some 3 billion humans and can lead to serious disease, including ulcers and cancer. Ottemann and her colleagues have discovered two of the first chemoreceptors known to aid in the process of bacterial colonization.

Many bacterial pathogens establish infection in a specific part of the body. For example, Salmonella typhimurium infects only the intestine, while the ulcer-causing bacterium Helicobacter pylori targets the stomach. Furthermore, some pathogens express specific subsets of genes only when inside host animals, and do not appear to express those genes under laboratory conditions.

How do pathogens know where they are, what to do, and when to do it? Evidence suggests that bacteria have sophisticated biochemical machinery for sensing the biochemical environment of their host and use this information to relocate to specific sites in their host where they have the best chance for their own survival.

To date, scientists have only been able to identify a few of the host conditions to which microbes respond. Enumerating such factors will not only provide insights into the basic science of bacteria, but may also help scientists identify new antibiotic targets to combat destructive pathogens.

H. pylori Is a Ubiquitous Bacterium that Targets its Host's Stomach

Karen Ottemann's research group examines how the bacterium H. pylori uses environmental clues to target the stomachs of its host. H. pylori infects some 3 billion people around the globe - approximately half the world's population. In the majority of cases, the bacterium establishes chronic infections. Conservative estimates suggest that 5% of those who are infected develop some form of serious illness, including ulcer disease, and gastric cancer.

Research groups like Ottemann's are now beginning to uncover the means by which H. pylori establishes and maintains infection. One crucial aspect in this process is the bacteria's ability to "swim" through the host animal's stomach to the mucous layer of the stomach lining, where it can live for decades. To accomplish this task, the pathogen uses organelles called flagella.

Evidence from Ottemann's group and others suggests that H. pylori does not swim randomly through its host, but instead moves systematically toward beneficial compounds and away from harmful ones. Proteins attached to the membrane surface of the bacteria, called chemoreceptors, are thought to act as the pathogen's environmental sensors.

H. pylori and its spaghetti-like flagella

The phenomenon of coupling environmental sensation and motility, called chemotaxis, and has been observed in vitro in many bacteria. However, determining the actual environmental cues and characterizing the molecular mechanisms that direct this process remain important challenges.

Ottemann's research group was the first to find chemoreceptors that play a role during H. pylori's colonization of its host. In order to accomplish this, they first constructed H. pylori mutants that were unable move or chemotax properly. Each of these strains were missing some but not all of their chemotactic-sensing abilities. They analyzed these mutants both in vitro and in a mouse infection model, and identified two distinct receptors that aid the process of infection. Both receptors are hypothesized to function by directly sensing environmental parameters and translating this information into a proper swimming response.

Research using such mutants also promises to provide insights into how to combat H. pylori. For example, if a strain lacking a specific chemoreceptor proves more susceptible to the host immune response, this would indicate that this chemoreceptor signals H. pylori to evade the elements of the response. Isolation of the receptor and a search for agents that block the receptor could then be tested to see whether host immunity improves.