Brucella species survive and replicate in host macrophages, causing chronic infections which can produce abortion and infertility in animals and a debilitating condition known as "undulant fever" in humans. Unfortunately, the mechanisms by which the brucellae establish and maintain their long term residence in host macrophages are presently unknown. The goal of the research being performed in our laboratory is to define the roles of individual gene products in allowing these bacteria to resist the environmental stresses they encounter in host macrophages. Two particular environmental stresses that are presently the focus of research in our laboratory are exposure to reactive oxygen and nitrogen species and iron deprivation. We are also examining the role of  small non-coding regulatory RNAs (sRNAs) in modulating virulence gene expression in Brucella. Results obtained from these studies will not only improve our understanding of the pathogenesis of Brucella infections, but also contribute significantly to our general knowledge concerning intracellular replication by bacterial pathogens.

Alcantara, R., R. A. Read, M. W. Valderas, T. D. Brown, and R. M. Roop II.  2004. Intact purine biosynthesis pathways are required for wild-type virulence of  Brucella abortus 2308 in the BALB/c mouse model. Infect. Immun. 72:4911-4917.

Gee, J. M., M. E. Kovach, V. K. Grippe, S. Hagius, J. V. Walker, P. H. Elzer, and R. M. Roop II. 2004. Role of  catalase in the virulence of  Brucella melitensis in pregnant goats. Vet. Microbiol. 102:111-115.

Gee, J. M., M. W. Valderas, M. E. Kovach, V. K. Grippe, G. T. Robertson, W.-L. Ng, J. M. Richardson, M. E. Winkler, and R. M. Roop II. 2005. The Brucella abortus Cu/Zn superoxide dismutase (SodC) is required for optimal resistance to oxidative killing by murine macrophages and wild type virulence in experimentally infected mice. Infect. Immun. 73:2873-2880.

Valderas, M. W., R. B. Alcantara, J. E. Baumgartner, B. H. Bellaire, G. T. Robertson, W.-L. Ng, J. M. Richardson, M. E. Winkler, and R. M. Roop II. 2005. Role of  HdeA in acid resistance and virulence in Brucella abortus 2308. Vet. Microbiol. 107:307-12.

Bellaire, B. H., R. M. Roop II, and J. A. Cardelli. 2005. Opsonized virulent Brucella abortus but not attenuated hfq or bacA mutants replicate within non-acidic, endoplasmic reticulum negative, LAMP 1 positive phagosomes in human monocytes. Infect. Immun. 73: 3702-3713.

Hornback, M. L., and R. M. Roop II. 2006. The Brucella abortus xthA-1 gene product participates in base excision repair and resistance to oxidative killing but is not required for wild-type virulence in the mouse model. J. Bacteriol. 188:1295-1300.

Roux, C. M., N. J. Booth, B. H. Bellaire, J. M. Gee, R. M. Roop II, M. E. Kovach, R. M. Tsolis, P. H. Elzer, and D. G. Ennis. 2006. RecA and RadA proteins of  Brucella abortus do not perform overlapping protective DNA repair functions from oxidative burst. J. Bacteriol. 188: 5187-5195.

Parent, M. A., R. Goenka, E. Murphy, K. LeVier, N. Carreiro, B. Golding, G. Ferguson, R. M. Roop II, G. C. Walker, and C. L. Baldwin. 2007. Brucella abortus bacA mutant induces greater pro-inflammatory cytokines than the wild-type parent strain. Microbes Infect. 9:55-62.

Paulley, J. T., E. S. Anderson and R. M. Roop II. 2007. Brucella abortus requires the heme transporter BhuA for maintenance of chronic infection in BALB/c mice. Infect. Immun. 75:5248-5254.

Anderson, E. S., J. T. Paulley and R. M. Roop II. 2008. The AraC-like transcriptional regulator DhbR is required for maximum expression of  the 2,3-dihydroxybenzoic acid biosynthesis genes in Brucella abortus 2308 in response to iron deprivation. J. Bacteriol. 190:1838-1842.

Khan, S. R., J. Gaines, R. M. Roop II, and S. K. Farrand. 2008. Broad host range expression vectors with tightly regulated promoters and their use for examining the influence of  TraR and TraM expression on Ti plasmid quorum sensing. Appl. Environ. Microbiol. 74: 5053-5062.

Anderson, E. S., J. T. Paulley, J. M. Gaines, M. W. Valderas, D. W. Martin, E. Menscher, T. D. Brown, C. S. Burns, and R. M. Roop II. 2009. The manganese transporter MntH is a critical virulence determinant in experimentally infected mice. Infect. Immun. 77:3466-3474.

Roop, R. M. II, J. M. Gaines, E. S. Anderson, C. C. Caswell, and D. W. Martin. 2009. Survival of  the fittest: how Brucella strains adapt to their intracellular niche in the host. Med. Microbiol. Immunol. 198:221-238.

Sengupta, D., A. Koblansky, J. Gaines, T. Brown, A. P. West, D. Zhang, T. Nishikawa, S.-G. Park, R. M. Roop II, and S. Ghosh. 2009. Subversion of  innate immune responses by Brucella through the targeted degradation of  the TLR signaling adapter, MAL. J. Immunol. (in press).

Sengupta, D., A. Koblansky, J. Gaines, T. Brown, A. P. West, D. Zhang, T. Nishikawa, S.-G. Park, R. M. Roop II, and S. Ghosh. 2010. Subversion of  innate immune responses by Brucella through the targeted degradation of  the TLR signaling adapter, MAL. J. Immunol. 184:956-964. 

Steele, K. H., J. E. Baumgartner, M. W. Valderas, and R. M. Roop II. 2010. A comparative study of  the roles of  AhpC and KatE as respiratory antioxidants in Brucella abortus 2308. J. Bacteriol. 192: 4912-4922. 

Anderson, E. S., J. T. Paulley, D. A. Martinson, J. M. Gaines, K. H. Steele, and R. M. Roop II. 2011. The iron responsive regulator Irr is required for wild-type expression of  the gene encoding the heme transporter BhuA in Brucella abortus 2308. J. Bacteriol. 193:5359-5364. 

Caswell, C. C., J. M. Gaines, and R. M. Roop II. 2012. The RNA chaperone Hfq independently coordinates expression of  the VirB type IV secretion system and the LuxR-type regulator BabR in Brucella abortus 2308. J. Bacteriol. (in press). 

Menscher, E. A., C. C. Caswell, E. S. Anderson, and R. M. Roop II. 2012. Mur regulates the gene encoding the manganese transporter MntH in Brucella abortus 2308. J. Bacteriol. (in press).