eTopics

eTopic 1.1 Clifford W. Houston: From Aquatic Pathogens to Outer Space: An Interview

Clifford W. Houston has taught medical microbiology for over two decades at the University of Texas Medical Branch (UTMB). Houston developed assays to detect toxins from group A streptococci and from Salmonella species. He showed how Aeromonas bacteria acquired from waterways can fatally infect wounds in humans. A leader in microbial education, he developed innovative outreach programs for UTMB, chaired the Education Board of the American Society for Microbiology (ASM), and was elected president of ASM in 2006. As deputy associate administrator for education at the National Aeronautics and Space Administration (NASA) in 2003, he addressed the medical challenges faced by astronauts and funded programs to inspire the next generation of explorers.

When did you first become interested in science?

I am a native of Oklahoma City, Oklahoma, and the first member of my family to attend college. My parents always encouraged me to obtain as much education as possible. My interest in science began when I did my first science fair project in elementary school. My teacher was very encouraging and gave me confidence that I could do the project. When I was in junior high school, I transformed the basement of my parents’ home into a research laboratory.

How did you decide to make a career in microbiology?

My first undergraduate course in microbiology had a significant impact on my life. I was inspired so much by the subject that I immediately changed my undergraduate major from biology to microbiology. It was my good fortune to have the opportunity to conduct my predoctoral studies in the laboratory of Joseph J. Ferretti, whose expertise is streptococcal genetics. In Ferretti’s laboratory, I worked on the kinetics and regulation of type A streptococcal exotoxin during the growth of Streptococcus pyogenes. This work resulted in one of my first publications in Infection and Immunity. Ferretti’s mentorship sustained my career interest in determining the role that bacterial toxins play in the pathogenesis of disease. I acquired my expertise in working with Gram-negative bacteria from Johnny Peterson as a postdoctoral fellow in his laboratory. As a faculty member, I was honored to have Ashok Chopra as a postdoctoral fellow; he conducted much of our work on Aeromonas.

You developed sensitive assays for detection of toxins from group A streptococci and from Salmonella. What are the special challenges of assay development for pathogens?

During the mid- to late 1970s, I modified the enzyme-linked immunosorbent assay (ELISA) to detect bacterial toxins that play a role in the pathogenesis of disease. The major challenges in developing this type of assay are sensitivity and specificity. I succeeded in developing an extremely sensitive assay (capable of detecting nanogram quantities), as well as an assay specific enough to avoid a high frequency of false positive reactions. The ability to detect these toxins can be used to link a pathogen to causation of human disease.

How did you choose to study Aeromonas hydrophila?

We were surveying the cultural filtrates of a variety of bacterial isolates in the laboratory employing an ELISA toxin assay using cholera antitoxin. To our surprise, the Aeromonas cultural filtrates tested positive in the ELISA, which meant that some antigen in the cultural filtrate cross-reacts with the cholera toxin.

Aeromonas is associated with wound infections and causes gastroenteritis. We found that a cytotoxic enterotoxin related to cholera toxin is associated with tissue damage in cell cultures and rabbit-skin testing, as well as fluid accumulation in rabbit intestinal loops. We also showed that Aeromonas with mutations in the cytotoxic enterotoxin gene has diminished virulence.

Is Aeromonas an opportunistic pathogen? Why are opportunistic pathogens a growing topic of concern for research and for public health?

Some species of Aeromonas may be pathogens, while others may be opportunists. Opportunistic microorganisms are capable of causing disease only when the conditions are favorable to the bacteria, such as when the host’s immune system has been weakened as a result of stress, radiation treatment, chemotherapy, or viral diseases. Opportunistic pathogens are a growing concern because they may live in the host for years, waiting for the opportunity to cause disease.

How does a patient contract illness from Aeromonas?

Aeromonas hydrophila originally was thought to infect only cold-blooded animals, such as frogs, snakes, and fish. However, there are many isolated cases of Aeromonas infections reported in the literature resulting from individuals whose skin has been cut, abraded, and/or punctured coming in contact with water contaminated with Aeromonas species. One case involved a motorcycle accident on the side of a highway in which the rider received a compound fracture in one of his legs and decided to put his injured leg into nearby pond water, which unfortunately contained Aeromonas species. From the pond, the microorganism entered his bloodstream, and the motorcyclist died in a hospital 48 hours later.

It is possible to acquire an Aeromonas infection from infected fish. For example, people have been infected by contaminated fish hooks or by handling infected fish when their hands that have cuts or abrasions. In addition, humans can get gastroenteritis by ingestion of Aeromonas-contaminated food.

What are your goals as an educator in microbiology?

My major goal is to expose young precollege and college students to the field of microbiology and to direct more students toward careers in the biomedical sciences. My Educational Outreach Office offers a summer research program for high school students. The students work in the laboratory of research faculty at the University of Texas Medical Branch. The students work 40 hours per week for seven weeks during the summer, get paid a stipend, and present a poster on their work at the end of the program. More than 95% of these students go on to college.

How did microbiology fit into your work at NASA?

I served on a team of NASA experts whose task was to plan the details on returning to the moon and [going] on to Mars. Microbiology will play an important role in our plans because NASA must be careful not to contaminate the moon or Mars with microorganisms from Earth, and vice versa. We are concerned with the impact of long-term space travel on the astronauts’ immune system and their susceptibility to infection. Also, there is concern about the impact of long-term exposure to UV light in causing mutations in harmless bacteria that make them virulent or antibiotic resistant.

Do you think the astronauts will find extraterrestrial microorganisms?

Recent data indicate that there may be water on Mars, which suggests the possibility that life may exist on the planet. Water will be examined for microorganisms as a first sign of life on the planet. Plans for isolation and containment have been discussed to prevent transporting Earth microorganisms to another planet because mutations might occur during the journey and the microorganisms could become more virulent. We also need to take precautions to prevent transporting extraterrestrial microorganisms back to Earth.

What do you think are the most exciting areas for students entering microbiology today?

The most exciting areas are astrobiology and biophysics. Both fields have relevance to microbiology. Another exciting area is biodefense. This field will play a significant role in the future protection of our country against biological warfare. Finally, another important field to remember is bioethics, which will always be a compelling career choice.

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Clifford Houston, professor of microbiology and immunology and associate vice president for educational outreach at the University of Texas Medical Branch at Galveston. Photo courtesy of Clifford W. Houston.

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Aeromonas sp. bacteria adhering to human epithelial cells. (Cell length, 2–4 lm.) Photo courtesy of Clifford W. Houston.

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Wound infections caused by Aeromonas hydrophila, in a human patient (left) and in a fish (right). Photo courtesy of Clifford W. Houston.