Interaction of virulent and non‐virulent Rhodococcus equi human isolates with phagocytes, fibroblast‐ and epithelial‐derived cells

Rhodococcus equi is a facultative, intracellular, Gram‐positive coccobacillus, increasingly reported in pneumonia of AIDS‐infected patients. We investigated killing resistance properties of human R. equi virulent and avirulent human strains. Avirulent β‐lactam‐susceptible strains had lower intracellular colony forming units after 45 min incubation in murine macrophages J774 and human monocyte‐macrophage TPH‐1 than those of virulent strains. Only virulent β‐lactam‐resistant strains persisted within macrophages for at least 18 min only. A β‐lactam‐resistant mutant was obtained from a β‐lactam‐susceptible strain after selection in a penicillin G‐containing culture medium. This mutant strain, like the natural virulent strains, persisted within macrophages, harboured cell‐associated appendages, produced phage‐like particles and induced, after its intravenous inoculation, a chronic infection in BALB/c nude mice. Supernatant culture of virulent strains transferred partial macrophage‐killing resistance properties to avirulent strains. The same supernatant was toxic for L‐929, HeLa and Vero cell cultures. These supernatant effects were heat‐inactivated, trypsin‐inactivated and did not seem to be linked to phage‐like particle presence. These data argue that virulence, β‐lactam‐resistance, and macrophage‐killing resistance are associated in human R. equi isolates. Moreover, only virulent strains produced uncharacterized toxic factors.