ABSTRACT
Density-dependent cell-cell communication, or quorum sensing (QS), has been demonstrated in numerous species of bacteria. The basic function of QS is likely to confer a nutritional advantage, particularly in a highly populated, mixed-species environment. QS also has ramifications on the production of colonization and virulence factors. Pheromone-like substances secreted into the extracellular milieu appear to govern many of the transcription products in these bacteria. At a high cell density, the QS systems are triggered, and the transcription of the colonization factors are suppressed and replaced by the expression of virulence factors. Major pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, have evolved with numerous QS circuits, which modulate the production of various toxins and regulate parallel QS systems. Several QS-modulating therapies, such as macrolide antibiotics, QS vaccines, and competitive QS inhibitors, have been investigated and may prove to be helpful in diminishing the translation of QS-directed toxins or by prematurely activating the QS response to alert the immune system to bacteria hiding in a low cell density. QS represents a recently discovered method of bacterial communication and population control, which may prove to be a unique mechanism to prevent, suppress, and/or treat infectious diseases.
Subject(s)
Anti-Bacterial Agents/pharmacology , Pseudomonas aeruginosa/drug effects , Quorum Sensing/drug effects , Signal Transduction/drug effects , Animals , Anti-Bacterial Agents/therapeutic use , Cell Communication/drug effects , Gene Expression Regulation, Bacterial , Pseudomonas Infections/prevention & control , Pseudomonas aeruginosa/physiology , Quorum Sensing/physiology , Signal Transduction/physiology , Staphylococcal Infections/prevention & control , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiologyABSTRACT
OBJECTIVES: To report the association between the protease inhibitor indinavir and the development of urolithiasis. METHODS: Case reports of three adult patients infected with the human immunodeficiency virus who developed surgical renal stones while being treated with indinavir are presented. RESULTS: Of the 3 patients requiring surgical intervention, stone analyses were available in 2. One stone revealed an inner core of an unidentifiable crystal surrounded by calcium oxalate, and another was found to have indinavir components as determined by thin-layer chromatography and gas chromatography-mass spectrometry. Metabolic evaluation of all 3 patients identified significant hypocitraturia as an isolated finding. CONCLUSIONS: The widely used protease inhibitor indinavir is associated with the development of urolithiasis and may act as a nidus for heterogeneous nucleation leading to the development of mixed urinary stones. Surgical intervention may be necessary in some cases. Underlying metabolic abnormalities may contribute to the increased incidence of stone formation. Urologists and other health care providers should be aware of this association, as combined medical and surgical intervention may be necessary.
Subject(s)
HIV Protease Inhibitors/adverse effects , Indinavir/adverse effects , Kidney Calculi/chemically induced , Adult , Female , HIV Protease Inhibitors/analysis , Humans , Indinavir/analysis , Kidney Calculi/chemistry , Male , Middle AgedABSTRACT
Ehrlichiosis is a recently described tick-borne disease characterized by headache, fever and chills, leukopenia, thrombocytopenia, and transaminase elevation. The presentation is similar to Rocky Mountain spotted fever but the rash is less frequently present in ehrlichiosis. The diagnosis is confirmed by elevated antibody titers to Ehrlichia chaffeensis or visualization of inclusions in white blood cells and the disease is easily cured with tetracyclines or chloramphenicol. Cases of ehrlichiosis are reported from southeastern, southcentral and midatlantic states. We report three cases of Ehrlichia infection acquired in Pulaski County and Fort Knox, KY during 1992-93.