Correlation between antibiotic resistance, phage-like particle presence, and virulence in Rhodococcus equi human isolates.
Rhodococcus equi is a gram-positive coccobacillus that appears to be emerging as a pulmonary pathogen in AIDS patients. In four human clinical isolates, two antibiotic resistance phenotypes were found to coexist: one beta-lactam resistant and the other beta-lactam susceptible. In vitro, beta-lactam-resistant mutants were obtained at a frequency of 1 x 10(-5) to 5 x 10(-5) from beta-lactam-susceptible strains on cephalothin-containing plates. Neither beta-lactamase nor plasmid DNA was detected in beta-lactam-resistant or -susceptible strains. The penicillin-binding protein patterns for the two types of strains were identical. Electron microscopy revealed that the beta-lactam-resistant strains possessed cell-surface-associated appendages and produced phage-like particles. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of total cell protein showed at least three additional bands of 42, 39, and 30 kDa found only in the beta-lactam-resistant strains. Testing for virulence in Swiss mice revealed that (i) phage-like-particle-producing strains had lower 50% lethal doses when injected intravenously in euthymic and nude mice than the non-phage-like-particle-producing strains did and (ii) intravenous inoculation of a sublethal dose (5 x 10(6) CFU) in nude mice led to chronic infection by the phage-like-particle-producing bacteria only. Finally, in vitro growth curves indicated that the phage-like-particle-producing strains possessed an ecological selection advantage. These results suggest that, among R. equi human isolates, the antibiotic resistance phenotype is associated with virulence and may be phage mediated.
Nordmann
P
P
Service de Microbiologie, Hôpital Raymond Poincaré, Faculté de Médecine Paris-Ouest, Université Paris 5, Garches, France.
Keller
M
M
Espinasse
F
F
Ronco
E
E
D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000382:microbiology; D000193:Actinomycetales Infections / Q000150:complications / Q000382:microbiology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001435:Bacteriophages / Q000648:ultrastructure; D004352:Drug Resistance, Microbial / Q000235:genetics; D005260:Female; D006801:Humans; D007769:Lactams; D051379:Mice; D008819:Mice, Nude; D008854:Microscopy, Electron; D009154:Mutation; D010641:Phenotype; D016929:Rhodococcus equi / Q000187:drug effects / Q000472:pathogenicity* / Q000648:ultrastructure; D014774:Virulence
D000900:Anti-Bacterial Agents; D007769:Lactams