Michael G. Malkowski, PhD, has received a National Institutes of Health grant to study an oral bacterium associated with periodontitis.

Malkowski Studying Oral Bacterium in Periodontitis

Published August 26, 2019

story by dirk hoffman

Michael G. Malkowski, PhD, professor and chair of structural biology, is part of a research team using National Institutes of Health funding to study an oral bacterium strongly associated with periodontitis.

“Understanding the molecular mechanisms of how these virulence factors function during immune invasion will lead to the development of new strategies to prevent and treat periodontitis. ”
Professor and chair of structural biology

The National Institute of Dental and Craniofacial Research has funded the five-year, $2 million study titled “Exploring New Virulence Factors of the Oral Spirochete Treponema Denticola.”

Malkowski, along with Chunhao Li, MD, PhD, professor in the Philips Institute for Oral Health Research in the School of Dentistry at Virginia Commonwealth University, are co-principal investigators on the study.

Pathogen Breaches Host Immune Defenses

The innate immune system is the first line of defense against microbial infections. In the oral cavity, the innate immune system is highly active and sustains the oral microbiota at the stage of symbiosis.

As a keystone pathogen, the oral bacterium Treponema denticola (Td) is highly motile and invasive, establishing itself at the forefront of subgingival plaques where it directly confronts host immune attacks, says Malkowski, co-principal investigator on the study.

Td is able to breach host immune defenses, survives, and even becomes predominant in the pocket when dysbiosis and inflammation worsens — for example in severe and refractory periodontitis.

Investigating Novel Virulence Factors

The underlying mechanisms remain largely unknown, according to Malkowski, who says Li’s previous research has discovered several novel virulence factors.

“The broader goals of our current study are to utilize X-ray crystallography, coupled with mutational and functional assays to understand the role that the oral sphirochete Td plays in the pathogenesis of periodontitis,” Malkowski says.

“We are investigating three novel virulence factors of Td: a cysteine protease, a sialidase, and a novel glycan,” he adds.

The study’s specific aims are to address the following three questions:

  • What is the molecular mechanism by which TDE0362 (a cysteine protease) impairs host neutrophil and complement activation?
  • How does TDE0471 (a sialidase) utilize host sialic acids to protect Td from complement killing?
  • How does glycosylation alter the innate immune response to Td flagellins?

Understanding Complexity of Periodontitis

“Completion of these studies will not only provide new insights into understanding the pathogenicity of Td at the molecular level, but also advance our current understanding of the uniqueness and complexity of periodontitis,” Malkowski says.

“One of the unique aspects about keystone pathogens is that while they trigger robust and hostile inflammation, they have also evolved complex mechanisms to evade host immune defenses, which allow them to thrive in the pocket, change symbiotic microbiota to dysbiosis, and cause tissue damage.”

“Understanding the molecular mechanisms of how these virulence factors function during immune invasion will lead to the development of new strategies to prevent and treat periodontitis,” Malkowski concludes.