Faculty Profile

Research interests:

We use a combination of genetic, molecular, biochemical, and genomic approaches to study several problems in bacteria.

Host specificity of Salmonella. The genus Salmonella enterica includes over 2500 distinct serovars that are a major cause of food poisoning. These Salmonella serovars infect different types of animals. Strains with new virulence properties may arise by changes in host-specificity that allow them to infect a new animal host. However, little is known about the genetic determinants of host-specificity in bacteria. To identify genes responsible for host-specific virulence traits, we developed methods to construct genetic hybrids between broad host range Salmonella serovar Typhimurium and the host-specific serovar Typhi. The results demonstrated that host-specificity is determined by multiple, unlinked genetic loci. Comparative genomics coupled with genetic approaches indicate that pseudogenes limit the host-range of Typhi. Identifying the genetic determinants of host-specificity may provide experimental approaches to limit the development and spread of virulent Salmonella strains in animals and the emergence of new infectious diseases.

Chromosome rearrangements. In contrast to most well studied bacteria including Salmonella serovar Typhimurium and E. coli, inversions between the seven rrn operons on the chromosome of host-specific Salmonella serovars occur at a high frequency. We are using genetic and molecular tools to determine why inversions occur so much more readily in host-specific pathogens, and whether inversions play a role in virulence.

Genetic exchange of exotoxin genes. Genes that encode exotoxins are often carried on phage. In collaboration with the Rohwer lab, we are studying the transfer of exotoxin genes in the environment. Phage can move the exotoxin genes between bacteria, converting avirulent bacteria into pathogens. This is a potent mechanism for evolution of new strains of pathogens and emerging infectious diseases. Preliminary experiments demonstrated that phage in the environment are an abundant source of exotoxin genes, including diptheria toxin, cholerae toxin, shiga toxin, etc. We have developed methods to determine where exotoxin genes are found in the environment, which phage and bacteria carry the exotoxin genes, and how often exotoxin genes are transferred between bacteria in the environment and in a mammalian host. We are coupling studies on phage from the environment with studies using a model phage/host system to measure the frequency of infection, recombination, and release of phage in the environment and within a mammalian host. By combining the numbers and sources of phage in the environment with the frequencies of phage exchange in the model system, we plan to develop mathematical models that predict the rates that exotoxin genes spread in nature.

Novel vaccines. In collaboration with Professors Roger Sabbadini and Kathleen McGuire, and the start-up Biotech company, Vaxiion Therapeutics, we are working a new approch for vaccination. Bacteria normally divide in the middle, producing two daugher cells. However, under certain conditions bacteria can be induced to divide near one end, budding off minicells that lack chromosomal DNA. Minicells are metabolically active, but they cannot reproduce because they lack chromosomal DNA. These properties make minicells very useful for vaccine delivery. They can deliver antigens both directly and upon expression in a eukaryotic host. They contain adjuvant properties necessary to stimulate immune responses, but they are unable to cause an infection because they cannot replicate. In addition, minicells are efficiently internalized and processed by antigen presenting cells, a critical step in the initiation of protective immune responses. We are presently developing minicell vaccines to protect against a number of microbial pathogens.

Some recent publications:

Helm, R. A., A. Lee, H. Christman, and S. Maloy. 2004. Genome rearrangements at rrn operons in Salmonella. Genetics 165(3): 951-959.

Helm, A. H., S. Porwollik, A. Stanley, S. Maloy, M. McClelland, W. Rabsch, and A. Eisenstark. 2004. Pigeon-associated strains of Salmonella enterica serovar Typhimurium phage type DT2 demonstrate characteristics of host-adapted Salmonella serovars. Infect Immun. 72(12): 7338-7341.

Maloy, S., and M. Schaechter, M. 2006. The era of microbiology: a Golden Phoenix. International Microbiol. 9: 1-7.

Brown, E. and S. Maloy. 2006. A facile probe for protein structure and function in vivo. BioTechniques 41: 721-724.

Books:

Maloy, S. 1989. Experimental Techniques in Bacterial Genetics. Jones and Bartlett Publishers, MA

Maloy, S., J. Cronan Jr., and D. Freifelder. 1994. Microbial Genetics, Second Edition. Jones and Bartlett Publishers, MA

Maloy, S., V. Stewart, and R. Taylor. 1996. Genetic Analysis of Pathogenic Bacteria. Cold Spring Harbor Laboratory Press, NY.

Curtiss, R., S. Maloy, M. Riley, T. Silhavy, and C. Squires. 2002. EcoSal: Cellular and Molecular Biology of Escherichia coli and Salmonella. American Society for Microbiology Press, Washington, DC

Hughes, K. and S. Maloy (Editors). 2007. Advanced Bacterial Genetics: Use of Transposons and Phage for Genomic Engineering. Methods Enzymol., vol. 421. Elsevier Inc. (In press)

Maloy, S., V. Stewart, and D. Freifelder. 2007. Microbial Genetics, Third Edition. Jones and Bartlett Publishers, MA. (In preparation)

Contact information:

Stanley Maloy
College of Sciences
San Diego State University
5500 Campanile Drive
San Diego, CA 92182-1010

TEL: (619) 594-5142
FAX: (619) 594-6381
EMAIL: smaloy@sciences.sdsu.edu