Chlamydia trachomatis is an obligate intracellular bacterium, which is the leading cause of acquired blindness and the most prevalent bacterial sexually transmitted infection worldwide. Chlamydiae exist in two distinct forms. The infectious spore-like elementary bodies (EBs) that invade host cells differentiate into non-infectious reticulate bodies (RBs) that replicate intracellularly within a modified membrane-bound vacuole called the inclusion. Under stress, Chlamydiae can enter a persistent state, in which aberrant bodies (ABs) with reduced metabolic activity are formed. Surprisingly little is known about the mechanisms employed by the bacteria to maintain and manipulate their environment within host cells. This thesis investigates the role of inorganic ions in sustaining the inclusion throughout the Chlamydia infection cycle. Potassium starvation of intracellular RBs either after specific ionophore treatment or inhibition of inward rectifying cellular potassium channels induced the formation of ABs, which no longer differentiated into infectious EBs. These data demonstrate an essential role for potassium during C.trachomatis replication. Analysis of live RBs, using a potassium sensitive fluorescent probe, illustrated that potassium is actively scavenged from the host cell. Furthermore, when bacteria undergo RB-EB differentiation accumulated potassium is released prior to inclusion lysis. Experimentally reducing potassium ion concentration at this stage caused cells to expel bacteria in bursts. This event is distinct from previously described extrusion mechanisms, where either the inclusion is released intact or the host cell is lysed. These data show that RBs actively accumulate potassium during replication, with starvation leading to persistence. Loss of potassium ions during re-differentiation into EBs suggests that potassium efflux has a role in triggering inclusion lysis or bacteria exit from the host cell.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:626656 |
| Date | January 2014 |
| Creators | Andrew, S. C. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1430699/ |
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