ROSEN HQ; Interscience Conference on Antimicrobial Agents and Chemotherapy (43rd: 2003: Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2003 Sep 14-17; 43: abstract no. 1777.

Univ. of Washington, Seattle, WA.

BACKGROUND: Pathogens must adjust to potentially deleterious elements of the immune response as they establish a niche in their hosts. We focused on stresses produced within the human neutrophil (PMN) phagosome and hypothesized that microbial adaptive changes would be reflected, in part, by altered patterns of gene transcription. Methods and RESULTS: Expression profiling identified approximately 70 Escherichia coli mRNA transcripts that change in abundance shortly after phagocytosis by PMN. A subgroup of genes with prominent increases in expression (up to ten-fold: ahpC, ahpF, dps, katG) are regulated by the OxyR transcription factor and code for proteins that protect cells from H[2]O[2]-related stress (alkyl hydroperoxidase, DNA binding protein of starvation, catalase). Expression changes in OxyR-regulated genes were not observed to the same degree when bacteria responded to phagocytosis by PMN deficient in H[2]O[2] production (CGD PMN). Disruption of oxyR rendered E. coli more susceptible to killing by normal but not by CGD PMN. Complementing the oxyR disruption with a plasmid containing wild-type oxyR, reversed the hypersusceptibility phenotype. Similarly, oxyR disruption conferred diminished virulence for E. coli in a murine model of ascending pyelonephritis and mouse virulence was restored by plasmid complementation. CONCLUSION: Products of E. coli genes regulated by the OxyR transcription factor confer relative resistance to killing by PMN and contribute to microbial virulence in a murine pyelonephritis model. We infer that H[2]O[2] generated within the PMN phagosome is cytotoxic to E. coli by mechanisms that can be modulated by cytosolic antioxidant proteins, thus suggesting that the cytotoxic events are cytosolic in location.

Publication Types:

• Meeting Abstracts

Keywords:

• Animals
• Catalase
• DNA-Binding Proteins
• Escherichia coli
• Escherichia coli Proteins
• Humans
• Mice
• Naphthalenes
• Neutrophils
• Phagocytosis
• Plasmids
• Transcription Factors
• Transcription, Genetic
• genetics
• immunology
• protect

Other ID:

• GWAIDS0026499

UI: 102266123

From Meeting Abstracts