James E. Graham, Ph.D.

James E. Graham, Ph.D.

Research Interests

  • Identifying factors produced by Mycobacterium tuberculosis bacteria when growing in human blood cells and lung tissues

  • Characterizing how pathogenic bacteria change to allow growth in different specific environments during infection

  • Understanding the roles of the complex bacterial communities that normally inhabit our bodies, and how they change with disease

Through understanding bacterial adaptation during infection, we can develop new strategies to control infectious diseases

Mycobacterium tuberculosis

My research involves efforts to increase our understanding of how total genetic and metabolic capacities of different bacteria allow adaptation to specialized environments. These environments vary widely for individual microbes both within hosts at different stages of interaction, and in transmission to new hosts. This work typically begins with analysis of bacterial gene expression, including the underlying biochemical mechanisms involved in regulation. These initial steps are facilitated by a technique I developed for identifying microbial RNAs in cells and tissues called "SCOTS".  Current work is focused on defining the significance of Mycobacterium tuberculosisadaptive responses that occur in response phagocytosis by human macrophages, during growth and non-replicating persistence in mouse and human lung tissues, and during transmission to new hosts via droplet nuclei.

Fig 1. One human macrophage infected by M. tuberculosis H37Rv at 72 h. (1000x)

GFE (Genome Fragment Enrichment)

Understanding how microbial genome capacity in natural bacterial communities contributes to survival and colonization of different niches can begin with examination of DNA content. This is facilitated by a second novel approach developed with collaborators at the U. S. EPA called “GFE” or Genome Fragment Enrichment. Relevant work in my laboratory characterizes the content and potential of microbial flora communities. Our other work combines global and specific metabolic studies with functional and comparative genomics to identify and define important interactions occurring between hosts and microbes that either lead to or prevent disease.

Bacterial volatiles and diagnosis of respiratory disease

Bacteria, like plants, all produce specific volatile compounds. Although the presence of specific volatile organic compounds (VOCs) in patient breath have been shown to be reliable indicators of different disease states, they are only just beginning to be used in medical diagnosis. We are interested in identifying bacterial metabolites and host cell products produced during infection that can be used to identify patients with specific respiratory infections. This research involves collaborations with UofL colleagues in the Chemical Engineering and Chemistry departments who have developed specific reactive coatings and sampling plate technologies for efficient and inexpensive breath testing in high risk regions around the world. This work is supported by the Bill and Melinda Gates Foundation. (seeGraham, J. E. 2013. "Bacterial Volatiles and Diagnosis of Respiratory Infections".)

Recent Publications

Dawson, D. R., Nydam, D., Price, C. T.,Graham, J. E., Cynamon, M., Divers, T. J, and J. B. Flamino. 2010. Effects of opsonization of Rhodococcus equion bacterial viability and  phagocyte activation. Am J Vet Res. 72: 1465-1475.

Graham, J. E., Wantland, N. B., Campbell, M., and M. G. Klotz. 2010. Characterizing bacterial gene expression in nitrogen cycle metabolism with RT-qPCR. Methods Enzymol. 496: 345-72.

Sheikh, A., Charles, R. C., Sharmeen, N., Rollins, S., Harris, J. B., Bhuiyan, M. S., Khanam, F., Bukka, A., Kalsy, A., Porwolli, S.,Brooks, W. A., LaRocques, R. C., Hohmann, E., Cravioto, A., Logvinenko, T. Calderwood, S. B., McClelland, M.Graham, J. E., Qadri, F., and E. T. Ryan. 2011. In vivo expression of Salmonella enterica serotype Typhi genes in the blood of patients with typhoid fever in Bangladesh. PLoS Negl Trop Dis 5: e1419.

Brinkworth, A. J., Malcom, D. S., Pedrosa, A. T., Roguska, K., Shahbazian, S.,Graham, J. E., Hayward, R. D., and R. A. Carabeo. 2011. Chlamydia trachomatis Slc1 is a Type III secretion chaperone that enhances the translocation of its invasion effector substrate TARP. Mol. Microbiol. 82:131-44.

Bukka, A. Price. C. T., Kernodle, D. A. andJ. E. Graham. 2012. Mycobacterium tuberculosis RNA expression patterns in sputum bacteria indicate secreted Esx factors contributing to growth are highly expressed in active disease . Frontiers in Microbiol. 2: 266-272.

Graham, J. E. 2013. Bacterial Volatiles and Diagnosis of Respiratory Infections. Adv. Appl. Microbiol.,82: 29-52.

Martins, R. P., Aguilar, C.,Graham, J. E., Carvaja, A., Bautista, R., Claros, M. G.,  and J. J. Garrido. 2013. Pig infections by Salmonella enterica serovar Typhimurium: an insight into the molecular mechanisms carried out in mesenteric lymph-nodes by host and pathogen. Vet Res. submitted.