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The infectious elementary body (EB) is internalized by target cells and differentiates into the replicative but non-infectious reticulate body (RB) in a membrane-bound intracellular compartment termed the inclusion 1, 2, 3.
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This organism undergoes a biphasic developmental cycle during the course of infection. Furthermore, the roles we have characterized for PBP2 and PBP3 in regulating specific steps in chlamydial cell division have not been described in other bacteria.Ĭhlamydia trachomatis is an obligate intracellular coccoid bacterium that is the leading cause of bacterial sexually transmitted infections. Our analyses indicate that the sequential action of PBP2 and PBP3 drives changes in peptidoglycan organization that are essential for the polarized division of these obligate intracellular bacteria. Consistent with their distinct roles in polarized division, peptidoglycan organization is different in cells treated with PBP2 and PBP3-specific inhibitors. Cells treated with inhibitors that prevent peptidoglycan synthesis or peptidoglycan crosslinking by penicillin-binding protein 2 (PBP2) are unable to initiate polarized division, while cells treated with inhibitors that prevent peptidoglycan crosslinking by penicillin-binding protein 3 (PBP3/FtsI) initiate polarized division, but the process arrests at an early stage of daughter cell growth. During division, peptidoglycan assembles at the pole of dividing Chlamydia trachomatis cells where daughter cell formation occurs, and peptidoglycan regulates at least two distinct steps in the polarized division of Chlamydia trachomatis and Chlamydia muridarum. aeruginosa and related Gram-negative bacteria are sought and our study provides templates to assist that process and allows us to discuss new ways of inhibiting PBPs.Chlamydia trachomatis serovar L2 and Chlamydia muridarum, which do not express FtsZ, undergo polarized cell division. Improved drugs to combat infections by P. aeruginosa is an important human pathogen, the structural data reveal the mode of action of the frontline antibiotic ceftazidime at the molecular level. The conserved binding mode of β-lactam-based inhibitors appears to extend to other PBPs, as suggested by a comparison of the PBP3/ceftazidime complex and the Escherichia coli PBP1b/ceftoxamine complex. The orientations of the two β-lactams in the active site and the key interactions formed between the ligands and PBP3 are similar despite differences in the two drugs, indicating a degree of flexibility in the binding site. Binding of either carbenicillin or ceftazidime to purified PBP3 increases the thermostability of the enzyme significantly and is associated with local conformational changes, which lead to a narrowing of the substrate-binding cleft. Overall, the structures of apo and acyl complexes are very similar however, variations in the orientation of the amino-terminal membrane-proximal domain relative to that of the carboxy-terminal transpeptidase domain indicate interdomain flexibility. We report the first crystal structures of a penicillin-binding protein (PBP), PBP3, from Pseudomonas aeruginosa in native form and covalently linked to two important β-lactam antibiotics, carbenicillin and ceftazidime.