Chlamydia trachomatis contains a conserved ϳ7.5-kb plasmid. Loss of the plasmid results in reduced glycogen accumulation, failure to activate TLR2, and reduced infectivity. We hypothesized that reduced infectivity functions as a means of selection for plasmid maintenance. We directly examined the biological significance of the reduced infectivity associated with plasmid deficiency by determining the relative fitness of plasmid-deficient CM972 versus that of wild-type C. muridarum Nigg in mixed inocula in vitro and in vivo. C. muridarum Nigg rapidly out-competed its plasmid-cured derivative CM972 in vitro but was not competitive with CM3.1, a derivative of CM972 that has reverted to a normal infectivity phenotype. C. muridarum Nigg also effectively competed with CM972 during lower and upper genital tract infection in the mouse, demonstrating that strong selective pressure for plasmid maintenance occurs during infection. The severity of oviduct inflammation and dilatation resulting from these mixed infections correlated directly with the amount of C. muridarum Nigg in the initial inoculum, confirming the role of the plasmid in virulence. Genetic characterization of CM972 and CM3.1 revealed no additional mutations (other than loss of the plasmid) to account for the reduced infectivity of CM972 and detected a single base substitution in TC_0236 in CM3.1 that may be responsible for its restored infectivity. These data demonstrate that a chlamydial strain that differs genetically from its wild-type parent only with respect to the lack of the chlamydial plasmid is unable to compete in vitro and in vivo, likely explaining the rarity of plasmid-deficient isolates in nature.

Disease caused by cytomegalovirus (CMV) infection can clinically manifest in a variety of ways in the immunodeficient host and lead to significant morbidity and mortality. Infections can be primary, occur as a result of reactivation of latent virus, or infection with a new strain of CMV. Cell-mediated immunity is the main defense against CMV disease. This component of the immune system is frequently affected in children who are born prematurely, have undergone solid organ transplantation or hematopoietic stem cell transplantation, or have infection with human immunodeficiency virus. Accordingly, these children are at increased risk for severe disease due to CMV. In addition, CMV itself alters cell-mediated immunity and may predispose hosts to other bacterial, fungal, or viral infections as well as predispose to graft rejection. The importance of CMV in these special populations of children, emphasizing epidemiology, risk factors, and preventive strategies, is reviewed.