Bacterial Physiology: Chlamydiae Play by Their Own Rules

RESEARCH HIGHLIGHTS

Nature Reviews Microbioology | AOP, published online 23 December 2013; doi:10.1038/nrmicro3198

BACTERIAL PHYSIOLOGY Chlamydiae play by their own rules Most bacteria possess a peptido- attempts to detect and purify pepti- septum of dividing cells, which is glycan sacculus (composed of a doglycan from these bacteria have consistent with the requirement for the amoeba disaccharide backbone crosslinked by failed. Pilhofer et al. used electron peptidoglycan synthesis prior to symbiont pentapeptide chains), which is crucial cryotomography to examine the cell division. Treatment of infected Protochlamydia for cell division, maintaining cell cell envelope of two deeply rooting mouse fibroblasts with inhibitors of shape and resisting osmotic stress. Chlamydiae, P. amoebophila and peptidoglycan synthesis led to the amoebophila Whether the obligate, intracellular Simkania negevensis. They found production of fewer C. trachomatis and the human Chlamydiae contain this structure that only P. amoebophila contained cells, which were enlarged, had aber- pathogen has long been debated, but two detectable peptidoglycan, and high- rant cell shapes and were unable to Chlamydia studies now show that two different pressure liquid chromatography divide. Furthermore, the dipeptide Chlamydia species, the amoeba sym- combined with mass spectrometry analogues were shown to rescue the trachomatis, biont Protochlamydia amoebophila showed that the muropeptides of C. trachomatis growth inhibition that do synthesize and the human pathogen Chlamydia purified sacculi contained an was induced by an inhibitor of the peptidoglycan trachomatis, do synthesize unknown modification that is absent dipeptide ligase, which confirms that peptidoglycan. in peptidoglycan from other Gram- they can be used as substitutes for the Some Chlamydiae encode a positive and Gram-negative bacteria. natural dipeptide. complete peptidoglycan biosynthesis Imaging of fluorescent D-amino Together, these studies provide pathway, and pathogenic strains are acid incorporation confirmed the the strongest evidence so far that sensitive to peptidoglycan-targeting synthesis of peptidoglycan in vivo, Chlamydiae possess peptidoglycan. β-lactam antibiotics; however, and treatment of infected amoebae However, although they seem to with an inhibitor of peptidoglycan play by the peptidoglycan rules, synthesis resulted in the formation Chlamydiae are still unique, as they of enlarged P. amoebophila cells and are the only example of bacteria that reduced infection rates. Together, contain functional peptidoglycan but these findings confirm that this lack the cytoskeletal protein FtsZ. Chlamydia species can synthesize a Considering that septal peptido unique type of peptidoglycan, which glycan synthesis is orchestrated has an important role during infec- by FtsZ, these findings challenge tion and in maintaining cell shape. the prevailing view that FtsZ is Liechti et al. developed a novel in essential in bacteria that possess vivo peptidoglycan labelling approach peptidoglycan. that used D-Ala–D-Ala dipeptide Christina Tobin Kåhrström analogue probes, to which modified ORIGINAL RESEARCH PAPERS Pilhofer, M. et al. fluorophores were attached by click Discovery of chlamydial peptidoglycan reveals chemistry. Using this method, the bacteria with murein sacculi but without FtsZ. Nature Comms. 4, 2856 (2013) | Liechti, G. W. et al. authors detected the presence of A new metabolic cell-wall labelling method Infected mouse fibroblast cells (nucleus in blue) peptidoglycan in C. trachomatis, reveals peptidoglycan in Chlamydia trachomatis. show that peptidoglycan (green) is synthesized by and found that most of the labelled Nature http://dx.doi.org/10.1038/nature12892 Chlamydia trachomatis cells (red). Image courtesy (2013) of E. Kuru, Indiana University, USA. peptidoglycan localized to the

NATURE REVIEWS | MICROBIOLOGY VOLUME 12 | FEBRUARY 2014