The oral cavity of healthy individuals contains hundreds of different bacterial, viral, and fungal species. Many of these can associate to form biofilms, which are resistant to mechanical stress or antibiotic treatment. Most are also commensal species, but they can become pathogenic in responses to changes in the environment or other triggers in the oral cavity, including the quality of an individual’s personal hygiene. The complexity of the oral microbiome is being characterized through the newly developed tools of metagenomics. How the microbiome of the oral cavity contributes to health and disease is attracting the interest of a growing number of cell biologists, microbiologists, and immunologists.

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Bacterial infections of the mucosal epithelium are a major cause of human disease. The prolonged presence of microbial pathogens stimulates inflammation of the local tissues, which leads to changes in the molecular composition of the extracellular milieu. A well-characterized molecule that is released to the extracellular milieu by stressed or infected cells is extracellular ATP and its ecto-enzymatic degradation products, which function as signaling molecules through ligation of purinergic receptors. There has been little information, however, on the effects of the extracellular metabolites on bacterial growth in inflamed tissues. Millimolar concentrations of ATP have been previously shown to inhibit irreversibly bacterial infection through ligation of P2X 7 receptors. We show here that the proinflammatory mediator, ATP, is released from Chlamydia trachomatis-infected epithelial cells. Moreover, further stimulation of the infected cells with micromolar extracellular ADP or ATP significantly impairs the growth of the bacteria, with a profile characteristic of the involvement of P2X 4 receptors. A specific role for P2X 4 was confirmed using cells overexpressing P2X 4 . The chlamydiae remain viable and return to normal growth kinetics after removal of the extracellular stimulus, similar to responses previously described for persistence of chlamydial infection. Danger signals comprise a varied group of extracellular molecules which indicate a potentially harmful physiological state and for which specific sensory mechanisms exist (38,40,51,55,56). Well-known danger signals include extracellular ATP, adenosine, uric acid crystals, the chromatin component HMGB1, and heat shock proteins. However, the level of danger posed elicits different cellular responses. For example, ATP is released from resting cells (nanomolar range) (5, 37), stressed and dying cells (micromolar range) (23), and physically compromised cells (millimolar range), although actual concentrations depend heavily on cell type and environment. Cells in the adjacent tissue must then decide whether to modify their own behavior in response to the extracellular signal, and whether to amplify the response by secreting other signaling molecules such as cytokines.The cells sense extracellular ATP and other nucleotides and nucleosides via a family of membrane receptors called purinergic receptors. These receptors are subdivided by function and homology into three classes: P2X are ligand-gated ion channels sensitive to ATP, P2Y are G-protein-coupled receptors stimulated by adenine and uracil nucleotides, and P1 receptors are also G protein coupled but are sensitive to adenosine (11,45). The tissue distribution and sensitivity to the ligands vary significantly within each family (12), such that slightly different concentrations of ligand can have different effects at a single cell type, and the same concentration of ligand can have contrasting effects on different cell types.While purinergic receptors have been best characterized in the central nervous system, the...

Following a high degree of suspicion with prompt initiation of antifungal agents and reversal of potential immunosuppressant therapies along with neurosurgical evacuation of intracranial collections or removal of infected hardware (CSF shunts) can lead to more optimistic outcomes of these complex clinical scenarios.

Emerging infectious diseases represent a major challenge to human health worldwide. The risk of evolving new infectious pathogens has been intensifying due to urbanization, demographic changes, air travel, inappropriate use of antibiotics, and climate change. These pathogens can affect humans from urban centers to the remotest corners of the globe. Far from being a scourge of the past, infectious diseases are relevant for the world today.