Dual consequence of mutation in the dihydrofolate reductase gene of Diplococcus pneumoniae.
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The patterns of colonization of D. pneumoniae were studied over a 46-month period in a group of young children in a day-care center. Forty-four percent of nasal cultures yielded D. pneumoniae. The most frequently isolated serotypes--6, 19, and 23--accounted for 49% of the isolates; the nine most common serotypes included 80% of the isolates. Individual serotypes frequently were carried for several months. Reacquisition of a serotype previously carried occurred frequently. There was limited spread of serotypes among the children despite prolonged contact.
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An experimental model is described which demonstrated increased susceptibility of mice to infection with D. pneumoniae following splenectomy. It was necessary to use small numbers of a particular strain of pneumococcus (D. pneumoniae type 6), intravenous infection and a particular strain of mouse (pathogen-free NCS strain). The increase in susceptibility persisted for at least 4 months after splenectomy. With modifications in experimental design such as use of large numbers of organisms, a different strain of pneumococcus, the intraperitoneal route of infection or a different mouse strain no increase or a much less impressive increase in susceptibility was demonstrated. Following intravenous injection of small numbers of D. pneumoniae Type 6 bacteremia tended to persist in all NCS mice. Multiplication of pneumococci subsequently occurred in a higher proportion of mice with splenectomy and at a more rapid rate than in control animals. Mice with splenectomy usually had more D. pneumoniae per ml of blood than per gram of any tissue. This suggested that in these mice multiplication of microorganisms occurs primarily in blood. In control mice higher concentrations of bacteria were present in spleen than in blood, and higher concentrations were found in blood than in other tissues. These results suggested that in normal mice infected intravenously with small numbers of D. pneumoniae Type 6, the spleen protects by removing and killing small but critical numbers of D. pneumoniae which are circulating in the blood. No evidence was found to suggest that the altered susceptibility is mediated by an effect of splenectomy on numbers of circulating leukocytes or on the antibacterial activity of mouse blood.
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