The long-term goal of these studies is to better understand cell division in the model organism Escherichia coli. A deeper understanding of bacterial cell division is expected to facilitate the development of new antibiotics and will therefore benefit public health. In E. coli, cell division is mediated by a structure called the """"""""septal ring,"""""""" which is known to contain about 20 proteins. An important challenge for the future will be to identify and characterize any proteins that are missing from the current model. The experiments proposed here concern three newly discovered E. coli septal ring proteins that carry a peptidoglycan binding domain known as a SPOR domain.
Specific Aim1 will explore the roles of the SPOR domain proteins during constriction.
Specific Aims 2 and 3 are based on the observation that the SPOR domains themselves localize to the division site. This implies that SPOR domains bind preferentially to septal peptidoglycan.
Aim 2 explores structural features of peptidoglycan that are recognized by SPOR domains.
Aim 3 defines the structure of the peptidoglycan binding site on a SPOR domain. Understanding how SPOR domains specifically target septal peptidoglycan might provide important insights into septal peptidoglycan synthesis.
The studies proposed here will lead to a greater understanding of bacterial cell division. That knowledge can be used to develop new antibiotics.
|Ransom, Eric M; Ellermeier, Craig D; Weiss, David S (2015) Use of mCherry Red fluorescent protein for studies of protein localization and gene expression in Clostridium difficile. Appl Environ Microbiol 81:1652-60|
|Yahashiri, Atsushi; Jorgenson, Matthew A; Weiss, David S (2015) Bacterial SPOR domains are recruited to septal peptidoglycan by binding to glycan strands that lack stem peptides. Proc Natl Acad Sci U S A 112:11347-52|
|Jorgenson, Matthew A; Chen, Yan; Yahashiri, Atsushi et al. (2014) The bacterial septal ring protein RlpA is a lytic transglycosylase that contributes to rod shape and daughter cell separation in Pseudomonas aeruginosa. Mol Microbiol 93:113-28|
|Ransom, Eric M; Williams, Kyle B; Weiss, David S et al. (2014) Identification and characterization of a gene cluster required for proper rod shape, cell division, and pathogenesis in Clostridium difficile. J Bacteriol 196:2290-300|
|Söderström, Bill; Skoog, Karl; Blom, Hans et al. (2014) Disassembly of the divisome in Escherichia coli: evidence that FtsZ dissociates before compartmentalization. Mol Microbiol 92:1-9|
|Williams, Kyle B; Yahashiri, Atsushi; Arends, S J Ryan et al. (2013) Nuclear magnetic resonance solution structure of the peptidoglycan-binding SPOR domain from Escherichia coli DamX: insights into septal localization. Biochemistry 52:627-39|
|Duncan, Tammi R; Yahashiri, Atsushi; Arends, S J Ryan et al. (2013) Identification of SPOR domain amino acids important for septal localization, peptidoglycan binding, and a disulfide bond in the cell division protein FtsN. J Bacteriol 195:5308-15|
|Weiss, David S (2013) Escherichia coli shapeshifters. J Bacteriol 195:2449-51|
|Arends, S J Ryan; Williams, Kyle; Scott, Renada J et al. (2010) Discovery and characterization of three new Escherichia coli septal ring proteins that contain a SPOR domain: DamX, DedD, and RlpA. J Bacteriol 192:242-55|