B.A. Pitzer College -1986
M.S. Albert Einstein College of Medicine - 1989
Ph.D. Albert Einstein College of Medicine - 1992
Postdoc Stanford University School of Medicine - 1992-95
Research Associate: Suat Cirillo
Postdoctoral Fellows: Madeleine Moule, Preeti Sule, Ronak Tilvawala and Hee-Jeong Yang
Graduate Students: Tonya Shepherd and Lanette Christensen Undergraduate Students: David Chavez, Ariana Ramirez
Bacterial Pathogenesis, Host-Pathogen Interactions at the Molecular and Cellular Level
Our laboratory is interested in the pathogenesis of bacterial lung infections particularly tuberculosis and Legionnaires' disease. We are examining the virulence mechanisms of bacteria using cellular, molecular and genetic techniques. Our primary research goal is to obtain a better understanding of the roles of the pathogen and host in disease. These studies should contribute to our understanding of host-pathogen interactions at the molecular and cellular level that can be used for prevention, treatment and diagnosis. We hope that through a better understanding of the mechanisms by which these organisms cause disease we can prevent some, if not all, of these infections in the future.
Mycobacterial research in our laboratory also focuses on the mechanisms involved in direct interactions with host cells or factors. We often use the rapid-growing mycobacteria Mycobacterium marinum as a model for tuberculosis due to its ease of use, but all studies are focused toward the important pathogenic mycobacteria, M. tuberculosis or M. avium. We have identified genetic and environmental factors that impact virulence of mycobacteria. Through the use of RICE, TnSeq and other molecular genetic strategies, we have identified many loci that are important for pathogenesis. As we develop a better understanding of the biological function of these genes we are gaining insight into the complexity of host-pathogen interactions during the different phases of disease.
Our laboratory has focused on investigation of the mechanisms of Legionella pneumophila infection of host cells and how these interactions impact their ability to cause disease. We have begun to identify both the bacterial and host genes involved in this process. By examining both sides of this interaction we hope to dissect it at the molecular and cellular levels. Clearly entry into macrophages is a complex process involving multiple bacterial and host cell components. We make mutations in both the bacterial and host genes involved to allow evaluation of each mechanism in subsequent intracellular events as well as the disease process. At present, we have identified many Legionella genes that play a role in host cell infection. The majority of these genes were identified through the use of a novel molecular approach, designated Replicating and Integrating Controlled Expression (RICE) systems. Many of the determinants isolated are involved in processing, secretion and regulation of proteins involved in entry. We have found that the Legionella strains currently used for investigation of pathogenesis differ in a number of genes that effect virulence. We have found that the differences affect adherence, entry, intracellular replication and virulence in animal models. These differences could play key roles in the sporadic epidemics caused by these bacteria.
In order to better understand host factors involved in disease, we use several model systems: macrophages, the amoeba A. castellanii, mice and guinea pigs. Since amoebae are single-celled and relatively easy to grow and maintain in the laboratory, they represent a useful model system for understanding bacterial virulence mechanisms. We have identified six L. pneumophila-resistant A. castellanii (Lra) clones. Proteomic analyses allowed identification of three proteins that differ between these mutants and wild-type amoebae. In addition, we have developed a selection that allows us to isolate populations of mammalian monocytic cells that lack receptor(s) of interest. This approach combined with microarray analysis of gene expression has allowed us to evaluate the role of receptors in host cell interactions. We have identified several host factors involved in interactions with pathogens and analyzed their function in transgenic mice. Through collaborations with other groups nationally, we recently completed the guinea pig genome sequence and are using the information obtained for high-throughput sequencing and Next Generation sequencing to analyze susceptibility and resistance to infection in guinea pigs, which represent a more human-like model for disease, as compared to most other small animal models. Thus, we are taking a multi-faceted approach to the understanding of the interactions of bacteria with phagocytes from the perspective of both the bacterium and its host.
Y. Zheng, T. Sambou, J.D. Cirillo, M. McClelland, H. Andrews-Polymenis (2013). EAL-domain containing protein STM2215 (rtn) is a cyclic di-GMP phosphodiesterase that is needed during Salmonella infection. Mol. Microbiol. In press.
V.E. Calderon, G.A. Valbuena, Y. Goez-Rivillas, B.M. Judy, M.B. Huante, P. Sutjita, R.K. Johnston, D.M. Estes, R.L. Hunter, J. Actor, J.D. Cirillo, J.J. Endsley (2013). A humanized mouse model of tuberculosis. PLoS One. 8:e63331. PMCID: PMC3656943.
H. Xie, J. Mire, Y. Kong, M.H. Chang, H.A. Hassounah, C.N. Thornton, J.C. Sacchettini, J.D. Cirillo, J. Rao (2012). Designing BlaC-specific probes for rapid fluorescence detection of tuberculosis. Nature Chem. 4:802-809. PMID:23000993.
H.K. Janagama, H. Hassounah, S.L.G. Cirillo, J.D. Cirillo (2011). Random inducible controlled expression (RICE) for identification of mycobacterial virulence genes. Tuberculosis. 91:S66-S68. PMCID: PMC3248965.
J.A. Hyde, E.H. Weening, M. Chang, J.P. Trzeciakowski, M. Hššk, J.D. Cirillo, J.T. Skare (2011). Bioluminescent imaging of Borrelia burgdorferi in vivo demonstrates fibronectin binding protein BBK32 is required for optimal colonization and dissemination in the host. Mol. Microbiol. 82:99-113. PMID: 21854463
L. Alibaud, Y. Rombouts, X. Trivelli, A. Burguiere, S.L.G. Cirillo, J.D. Cirillo, J.-F. Dubremetz, Y. Guerardel, G. Lutfalla, L. Kremer (2011). A Mycobacterium marinum mutant defective for major cell wall associated lipids is highly attenuated in Dictyostelium discoideum and zebrafish embryos. Mol. Microbiol. 80:919-934. PMID:21375593
R. Kapoor, P.R. Eimerman, J.W. Hardy, J.D. Cirillo, C.H. Contag, A.E. Barron (2011). Efficacy of antimicrobial peptoids against Mycobacterium. Antimicrob. Agents Chemother. 55:3058-3062. PMCID: PMC3101442
Y. Kong, H. Yao, H. Ren, S. Subbian, S.L.G. Cirillo, J.C. Sacchettini, J. Rao, J.D. Cirillo (2010). Imaging tuberculosis with endogenous ?-lactamase reporter enzyme fluorescence. PNAS 107:12239-12244. PMCID: PMC2901431.
M. Khounlotham, S. Subbian, R. Smith III, S.L.G. Cirillo, J.D. Cirillo (2009). Mycobacterium tuberculosis modulates the host response to infection through the murine EphA2 receptor. J. Infect. Dis. 199:1797-1806. PMID: 19426113
S.L.G. Cirillo, S. Subbian, B. Chen, T.R. Weisbrod, W.R. Jacobs, Jr., J.D. Cirillo (2009). Protection of Mycobacterium tuberculosis from reactive oxygen species conferred by the mel2 locus impacts persistence and dissemination. Infect. Immun. 77:2557-2567. PMCID:ÊPMC2687327.
J. Lee, C. Attila, S.L.G. Cirillo, J.D. Cirillo, T.K. Wood (2009). Indole and 7-hydroxyindole diminish Pseudomonas aeruginosa virulence. Microbial Biotechnol. 2:75-90.
S. Tachado, M.M. Samrakandi, J.D. Cirillo (2008). Non-opsonic phagocytosis of Legionella pneumophila by macrophages is mediated by phosphatidylinositol 3-kinase. PLoS One. 3:e3324. PMCID: PMC2553182
B. Park, S. Subbian, S.H. El-Etr, S.L.G. Cirillo, J.D. Cirillo (2008). Use of gene dosage effects for a whole-genome screen to identify Mycobacterium marinum macrophage infection loci. Infect. Immun. 76:3100-3115.
C. Attila, A. Ueda, S.L.G. Cirillo, J.D. Cirillo, W. Chen and T.K. Wood (2008). Pseudomonas aeruginosa PA01 virulence factors and poplar tree response in the rhizosphere. Microb. Biotech. 1:17-29.
R. Bartzatt, S.L.G. Cirillo, J.D. Cirillo (2008) Determination of the molecular properties effectuating the growth inhibition of Mycobacterium tuberculosis by various small molecule hydrazides. Lett. Drug Des. Disc. 5:162-168.
L. Danelishvili, M. Wu, B. Stang, M. Harriff, S.L.G. Cirillo, J.D. Cirillo, R. Bildfell, B. Arbogast, L.E. Bermudez (2007). Identification of Mycobacterium avium pathogenicity island important for macrophage and amoeba infection. PNAS 104:11038-11043.
S. Subbian, P.K. Mehta, S.L.G. Cirillo and J.D. Cirillo (2007). The Mycobacterium marinum mel2 locus displays similarity to bacterial bioluminescence systems and plays a role in defense against reactive oxygen and nitrogen species. BMC Microbiol. 7:4.
S. Subbian, P.K. Mehta, L.E. Bermudez, S.L.G. Cirillo, J.D. Cirillo (2007). A Mycobacterium marinum mel2 mutant is defective for growth in macrophages producing reactive oxygen and nitrogen species. Infect. Immun. 75:127-134.
R. Bartzatt, S.L.G. Cirillo, J.D. Cirillo (2007). Antibacterial Activity of Dipeptide Constructs of Acetylsalicylic Acid and Nicotinic Acid. Drug Del. 14:105-109.
P.K. Mehta, A.K. Pandey, S. Subbian, S.H. El-Etr, S.L.G. Cirillo, M.M. Samrakandi, J.D. Cirillo (2006). Identification of Mycobacterium marinum Macrophage Infection Mutants. Microb. Pathogen. 40:139-151. PMID: 16451826
E. Miltner, K. Daroogheh, P.K. Mehta, S.L.G. Cirillo, J.D. Cirillo, L.E. Bermudez (2005). Identification of Mycobacterium avium Genes That Affect Invasion of the Intestinal Epithelium. Infect. Immun. 73:4214-4221.
S.H. El-Etr, S. Subbian, S.L.G. Cirillo, J.D. Cirillo (2004). Identification of Two Mycobacterium marinum Loci That Affect Interactions With Macrophages. Infect. Immun. 72:6902-6913.
M.M. Samrakandi, C. Zhang, M. Zhang, J. Nietfeldt, G. Duhamel, M.E. Olsen, P. Iwen, S. Hinrichs, P. Fey, J.D. Cirillo, A.K. Benson (2004). Genome Reduction During Divergence of Francisella tularensis subspecies tularensis and Francisella tularensis subspecies holarctica. FEMS Microbiol. Lett. 237:9-17.
L. Yan, R. Cerny and J.D. Cirillo (2004). Evidence that hsp90 Is Involved in the Altered Interactions of Acanthamoeba castellanii Variants with Bacteria. Eukaryot. Cell. 3:567-578.
L. Yan and J.D. Cirillo (2004). Infection of Murine Macrophage Cell Lines by Legionella pneumophila. FEMS Microbiol. Lett. 230:147-152.
D.A. Ridenour, S.L.G. Cirillo, F. Sheng, M.M. Samrakandi, J.D. Cirillo (2003). Identification of a Gene That Affects the Efficiency of Host Cell Infection by Legionella pneumophila in a Temperature-Dependent Fashion. Infect. Immun. 71:6256-6263.
S.L.G. Cirillo, L. Yan, M. Littman, M.M. Samrakandi, J.D. Cirillo (2002). Role of the Legionella pneumophila rtxA Gene in Amoebae. Microbiol. 148:1667-1677.
N.B. Harris, D.K. Zinniel, M.K. Hseih, J.D. Cirillo, R.G. Barletta (2002). Cell Sorting of Formalin-Treated Pathogenic Mycobacterium paratuberculosis Expressing GFP. Biotechniques 32:522-527.
M.M. Samrakandi, S.L.G. Cirillo, D.A. Ridenour, L.E. Bermudez, J.D. Cirillo (2002). Genetic and Phenotypic Differences Between Legionella pneumophila Strains. J. Clin. Microbiol. 40:1352-1362.
S.L.G. Cirillo, L.E. Bermudez, S.H. El-Etr, G.E. Duhamel and J.D. Cirillo (2001). The Legionella pneumophila Entry Gene rtxA is Involved in Virulence. Infect. Immun. 69:508-517.