B. fragilis is the most frequent opportunistic anaerobe pathogen isolated from human infections. The success of B. fragilis pathogenicity is still not completely understood. In general, Bacteroides infections occur as a consequence of a disruption in the integrity of the intestinal mucosa wall resulting from conditions such as gastrointestinal surgery, perforated or gangrenous appendicitis, perforated ulcer, diverticulitis, trauma and inflammatory bowel disease.Despite being only 0.5 - 1% of the intestinal microbial flora which typically contains 10¹¹ to 10¹² anaerobic bacteria per gram of stool, B. fragilis accounts for 50 to 70 % of all anaerobes isolated from human infections such as, intra-abdominal abscesses, infections of the female genital tract, deep wounds, brain abscesses, bacteremia, and midgestation infectious abortion. Because of this extraordinary paradox, understanding the mechanisms by which B. fragilis break away from the colon to cause systemic disease and death in humans is an extremely important scientific objective.We have found that B. fragilis produces nine hemolysins/cytolysins and their role in B. fragilis pathogenicity is poorly understood. Hemolysins/cytolysins are powerful virulence factors in both Gram positive and Gram negative bacteria. Moreover, bacterial cytolysins/hemolysins play an important role in the equilibrium control of the microbial ecosystem population associated with eukaryotic hosts due to their cytolytic/bactericidal properties which are used to inhibit other prokaryotes and eukaryotes in highly competitive ecological systems. In this regard, current research aims to investigate the role and function of this extensive number of hemolysins/cytolysins in Bacteroides species play in the establishment of infectious process and also their contribution to the ability of Bacteroides to dominate and take over the colonization of the human large intestinal tract.

Rocha, E. R., Tzianabos, A. O. and Smith, C. J. 2007. Thioredoxin reductase is essential for the thiol/disulfide redox control and oxidative stress survival in the anaerobe Bacteroides fragilis. J. Bacteriol. 189:8015-8023.

Sund, C. J., Rocha, E. R., Tzinabos, A. O., Wells, W. J., Gee, J. M., Reott, M. A., O’Rourke D. P. and Smith, C. J. 2008. The Bacteroides fragilis Transcriptome Response to Oxygen and H₂O₂: TheRole Of OxyR And Its Effect On Survival And Virulence. Mol. Microbiol. 67:129-142.

Robertson, K. P., Smith, C. J., Gough, A. M. and Rocha, E. R. 2006. Characterization of Bacteroides fragilis hemolysins and regulation and synergistic interactions of HlyA and HlyB. Infect Immun. 74:2304-2316.

Dana S. Wade, M. Worth Calfee, Edson R. Rocha, Elizabeth A. Ling, Elana Engstrom, James P. Coleman, and Everett C. Pesci. 2005. Regulation of Pseudomonas quinolone synthesis in Pseudomonasaeruginosa. J. Bacteriol. 187:4372-4380.

Rocha, E. R. and C. J. Smith. 2004. Transcriptional regulation of Bacteroides fragilis ferritin gene (ftnA) by redox-stress. Miccrobiology 150:2125-2134.

Diniz, C. G., Farias, L. M., Carvalho, M. A., Rocha, E. R. and Smith, C. J. 2004. Differential gene expression in a Bacteroides fragilis metronidazole-resistant mutant. J. Antimicrob. Chemother. 54:100-108.

Herren, C. D., Rocha, E. R. and C. J. Smith. 2003. Genetic analysis of an important oxidative stress locus in the anaerobe Bacteroides fragilis. Gene 316:167-175.

Rocha, E. R., C. D. Herren, D. J. Smalley and C. J. Smith. 2003. The complex oxidative stress response of Bacteroides fragilis: the roleof OxyR in control of gene expression. Anaereobe 9:165-173.

Smalley, D., Rocha, E. R., and Smith, C. J. 2002. Aerobic-type ribonucleotide reductase in the anaerobe Bacteroides fragilis. J. Bacteriol. 184:895-903.

Rocha, E.R., Smith, A., Smith, C.J. and J.H. Brock. 2001. Growth inhibition of Bacteroides fragilis by hemopexin: Proteolytic degradation of hemopexin to overcome heme limitation. FEMS Microbiol. Lett. 199:73-78.

Bayley, D. P., E. R. Rocha, and C. J. Smith. 2000. Analysis of cepA and other Bacteroides fragilis genes reveals a unique promoter structure. FEMS Microbiol. Lett. 193:149-154.

Rocha, E. R., G. Owens Jr., and C. J. Smith. 2000. The redox-sensitive transcriptional activator OxyR regulates the peroxide response regulon in the obligate anaerobe Bacteroides fragilis. J. Bacteriol. 182:5059-5069.

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