Michael Sebert
Assistant Professor, Dept of Pediatrics

Microbiology, Virology and Parasitology Program

Address

1202C Abramson Bldg (office)
1205B Abramson Bldg (lab)
3615 Civic Center Blvd
Philadelphia, PA 19104-4318

Office tel.: 267-426-0273
Lab tel.: 267-426-7258
Fax: 215-590-2025
E-mail: sebert@email.chop.edu

Duke University: BS (Zoology), 1990.

Stanford University: MD (Medicine), 1995.

Research Interests

• Pneumococcal pathogenesis, regulation of bacterial virulence determinants.

Key words: Streptococcus pneumoniae, bacterial pathogenesis, two-component signaling systems, transformation, quorum sensing.

Description of Research

My laboratory studies the coordinated genetic responses through which Streptococcus pneumoniae becomes adapted for survival in the upper respiratory tract. This Gram-positive bacterium, also known as the pneumococcus, causes a range of diseases including pneumonia, sepsis and meningitis. All of these infections are preceded by colonization of the nasopharynx, which constitutes the essential first interaction between this pathogen and its host.

The pneumococcus has 13 complete two-component signaling systems through which it senses and responds to environmental stimuli. One of these systems, designated CiaRH, is required for colonization as well as for the development of invasive disease. My colleagues and I have recently shown that expression of HtrA, a serine protease on the bacterial surface, is regulated by the CiaRH system and that this protease functions as an intermediary linking CiaRH to another pneumococcal signaling system. This second system, ComDE, is best characterized as controlling the development of natural competence for genetic transformation—as well as influencing the expression of numerous other genes not required for transformation—by sensing the accumulation of a peptide pheromone produced by the pneumococcus. Activation of CiaRH inhibits the development of competence via the proteolytic activity of HtrA; identification of the target protein through which this effect is mediated is an area of investigation in the laboratory.

The observations that CiaRH and HtrA both contribute to the fitness of S. pneumoniae in colonizing the nasopharynx and that similar quorum-sensing systems have been shown to affect virulence in other bacteria have motivated efforts in the laboratory to investigate the role of the competence pathway during pneumococcal colonization. A genetic approach using mutations designed to activate or inactivate the competence system at different points in the pathway is being employed to address this question. The natural pattern of competence activation during colonization is being assessed by measuring in vivo bacterial gene expression as well as through in vivo genetic transformation assays. Studies of the adherence of S. pneumoniae to cultured pharyngeal cells are being used to investigate the effects of these signaling pathways on the interaction of pneumococcus with the mucosal surface on which it lives.

Selected Publications

Kowalko, J.E., Sebert, M.E.: The Streptococcus pneumoniae competence regulatory system influences respiratory tract colonization. Infection and Immunity, 76:3131-3140, 2008.

Sebert, M.E., Patel, K.P., Plotnick, M., Weiser, J.N.: Pneumococcal HtrA protease mediates inhibition of competence by the CiaRH two-component signaling system. Journal of Bacteriology, 187:3969-3979, 2005.

Sebert, M.E., Palmer, L.M., Rosenberg, M., Weiser, J.N.: Microarray-based identification of htrA, a Streptococcus pneumoniae gene that is regulated by the CiaRH two-component system and contributes to nasopharyngeal colonization. Infection and Immunity 70:4059-4067, 2002.

Search PubMed for more articles

Lab

Rotation Projects

• Please contact Dr. Sebert directly to discuss current rotation projects.

Lab personnel:

Kathleen Stevens—research technician