Abstract
Human diseases caused by obligate intracellular bacterial pathogens result in significant morbidity and mortality. Obligate intracellular bacteria that replicate in the cytoplasm of host endothelial cells include Rickettsia prowazekii, Rickettsia rickettsii, and Orientia tsutsugamushi (etiologic agents of epidemic typhus, Rocky Mountain spotted fever, and scrub typhus, respectively). Residing in specialized vacuolar compartments are Anaplasma phagocyophilum and Ehrlichia chaffensis (agents of febrile illnesses that have tropisms for neutrophils and monocytes, respectively) and Chlamydia trachomatis, which targets mucosal epithelia and causes blinding trachoma and sexually transmitted diseases. Coxiella burnetii preferentially colonizes mononuclear phagocytes during natural infection where it inhabits a specialized vacuole with properties of a phagolysosome [1]. The pathogen causes a debilitating influenza-like illness in humans called Q (query) fever, a disease that has received recent notoriety due to a large outbreak in the Netherlands [2]. The absolute reliance of obligates on a eucaryotic host cell for growth imposes significant experimental constraints, not the least of which is difficulty in establishing pathogen genetic systems. However, C. burnetii was recently liberated from its host cell by a medium that supports axenic (host cell–free) growth. Here, we provide a brief overview of the systematic approach used in C. burnetii media development and discuss how insight gained from this success could facilitate development of axenic media for other obligate intracellular bacterial pathogens.
Highlights
Human diseases caused by obligate intracellular bacterial pathogens result in significant morbidity and mortality
We provide a brief overview of the systematic approach used in C. burnetii media development and discuss how insight gained from this success could facilitate development of axenic media for other obligate intracellular bacterial pathogens
The critical finding that the Coxiella-containing vacuole (CCV) resembles a phagolysosome [3] led to several reports showing metabolic activity of purified bacteria was optimal under moderately acidic conditions [4]
Summary
Human diseases caused by obligate intracellular bacterial pathogens result in significant morbidity and mortality. C. burnetii was recently liberated from its host cell by a medium that supports axenic (host cell–free) growth. We provide a brief overview of the systematic approach used in C. burnetii media development and discuss how insight gained from this success could facilitate development of axenic media for other obligate intracellular bacterial pathogens. Prior metabolic studies of host cell–free C. burnetii and knowledge of pathogen-host interactions provided a foundation on which to base initial media formulations. The critical finding that the Coxiella-containing vacuole (CCV) resembles a phagolysosome [3] led to several reports showing metabolic activity of purified bacteria was optimal under moderately acidic conditions The cellular microbiology and known metabolic properties of other obligates provide insight into conditions that might support axenic growth. Rickettsia spp. replicate in the well-defined milieu of the host cytoplasm and, similar to C. trachomatis, scavenge ATP from the host via the activity of an ATP/ADP translocase [14]
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