Chlamydia co-opts the rod-shape determining proteins MreB and Pbp2 for cell division.

Chlamydia notably lack the tubulin homolog FtsZ used for cytokinesis in most bacteria, so it has been a mystery how chlamydial reticulate bodies (RBs) divide by binary fission. This study provides evidence that in the absence of FtsZ, chlamydia use the actin homolog MreB to orchestrate cytokinesis.

MreB is normally used to maintain rod shape in those bacteria that have it, but the replicative form of chlamydia RBs are coccoid, suggesting that chlamydial MreB is used for another cellular process. Although determining chlamydial genetics is not yet possible, the authors exploit various drugs that target specific proteins including MreB and the high molecular weight (HMW) penicillin-binding proteins PBP2 and PBP3 to generate phenotypes that indicate that these proteins are important for chlamydial growth and cell division. Additional support for the involvement of these proteins in cytokinesis comes from their interaction with the cell division protein homolog FtsK. The evidence from this study is consistent with the idea that chlamydia are sensitive to β-lactam antibiotics (despite having no detectable peptidoglycan cell wall) because peptidoglycan is used exclusively to make a division septum using MreB, PBP2 and PBP3. More work will be needed for a mechanistic understanding of how MreB can take the place of FtsZ in this organism.

Vive la difference!

Chlamydiae are obligate intracellular pathogens with a highly reduced genome; they lack a gene for FtsZ but encode two penicillin-binding proteins (PBPs) needed for peptidoglycan (PG) synthesis. The absence of FtsZ is noteworthy because this nearly universal bacterial GTPase is generally required for cell division. Conversely, the presence of the PBPs is noteworthy because nobody has ever been able to find any PG associated with Chlamydia, although the fact that these organisms are penicillin-sensitive has long been taken as evidence that a small amount of a PG-like molecule must be present {1,2}.

Ouellette et al. used small molecule inhibitors to target the two PBPs and an actin-like protein named MreB. The results are most clear-cut in the case of a protein they designate as PBP3 (because it is similar to a PBP of the same name required for cell division in Escherichia coli). When PBP3 was inactivated, the normally round reticulate bodies became oblong, implying that septation was impaired. Inactivating either PBP2 or MreB, both of which are critical for elongation in many bacteria, resulted in more complex morphological changes that the authors argue are probably linked primarily to cell division. In summary, this is the first molecular analysis of cell division in Chlamydia, and it has produced two very provocative results — MreB probably substitutes for FtsZ, while both PBPs likely contribute to synthesis of some form of PG in the division septum.