Role of L-forms of Nocardia caviae in the development of chronic mycetomas in normal and immunodeficient murine models.

Single-cell suspensions of Nocardia caviae 112 were injected into normal, athymic, and asplenic mice by several different routes. The 50% lethal dose values, kill curve characteristics, histological and electron microscopic properties, organ clearance patterns, and induction of L-forms during the acute and chronic phase of disease were determined in groups of mice for up to 2 years after infection. From these data we concluded the following. (i) Athymic and asplenic animals were significantly more susceptible to N. caviae than their littermate controls regardless of inoculation route. (ii) All mice were most susceptible to lethal infection after intranasal administration and least affected when the organisms were injected into the peritoneal cavity. (iii) Chronic, progressive disease leading to the formation of mycetomas occurred only in mice injected intravenously. (iv) T-cell-deficient animals were impaired in the development of typical mycetomas. (v) L-forms of N. caviae were induced within immunocompetent hosts, whereas the cell wall-less state of the bacteria was not observed in the immunodeficient animals. (vi) Two colony types of the cell wall-deficient state were isolated from infected animals. (vii) These cell wall-deficient organisms were intimately involved in the pathogenesis of disease and bacterial persistence within the host. Finally (viii), with this strain of Nocardia, cell wall-deficient organisms played a major role in the development of the characteristic bacterial granule formed within the mycetomatous lesions 6 months to 1 year after intravenous inoculation.