Dynamics of the bacterial type IX secretion system and its effect on subgingival biofilm formation by bacteria of the human oral microbiome - Project Summary/Abstract
The bacterial Type IX protein secretion system (T9SS), which is a recently discovered protein secretion
system, is found in bacteria that are a part of human subgingival biofilms. So far, it has been shown that
T9SS is functional in Porphyromonas gingivalis [1, 2], Tannerella forsythia [3] and Capnocytophaga sp.
[4]. P. gingivalis Arg-gingipain (Rgp) and Lys-gingipain (Kgp) are secreted via T9SS. Rgp and Kgp
increase the risk of periodontal diseases by disrupting the host immune response and degradation of the
host tissue and plasma proteins. T9SS is associated with a rotary motor and its dynamics enables
secretion of cell-surface adhesins, known virulence factors and enzymes. It is also required for
movement of bacteria over a surface by a process called gliding motility. Cell adhesion, surface
navigation and motility are important for the formation of many bacterial biofilms [5]. Recent reports
suggest that bacterial motility machineries enable sensing of external surfaces via a process called as
mechanosensing [6, 7]. Human pathogens such as Escherichia coli and Salmonella enterica sense
external surfaces via the flagellar motor-Type III secretion system machinery [6], while Pseudomonas
aeruginosa and Myxococcus xanthus sense external surface via the Type IV pili machinery [7, 8]. Our
preliminary and published results suggest that gliding bacteria with T9SS have the ability to sense
external surfaces and viscous environments [9]. Such bacteria do not have the flagellar motor or the type
IV pili. Amongst bacteria of the human oral microbiome, members of Capnocytophaga genus, which are
present in human subgingival biofilms [10], are an attractive system for answering important questions
related to biofilm formation, surface-sensing, and hydrodynamics. These bacteria have the T9SS and
they exhibit gliding motility over external surfaces. Recently, genetic tools were developed for their
manipulation [4]. I propose to study Capnocytophaga gingivalis, which is an important, yet understudied
bacterium present in human subgingival biofilms [4, 10]. We discovered that the T9SS of C. gingivalis is
powered by a novel rotary motor. Also, we found that C. gingivalis cells use adhesins secreted by T9SS
to aggregate and form groups. Such aggregates exhibit gliding motility over external surfaces. Our data
suggests that gliding is powered by the same rotary motor that powers secretion via T9SS. Gliding
motility, which is the output of the dynamics of T9SS, will be used to assay for gene regulation and for
development of genetic screens. Such screens will be targeted towards identification of proteins involved
in sensory transduction by oral bacteria. Overall, dynamics of T9SS and role of proteins secreted by
T9SS will be studied in the context of subgingival biofilm formation.
