Characterization of the interaction between Yersinia enterocolitica biotype 1A and phagocytes and epithelial cells in vitro

Yersinia enterocolitica strains of biotype 1A are increasingly being recogn ized as etiological agents of gastroenteritis. However, the mechanisms by w hich these bacteria cause disease differ from those of highly invasive, vir ulence plasmid-bearing Y. enterocolitica strains and are poorly understood. We have investigated several biotype 1A strains of diverse origin for thei r ability to resist killing by professional phagocytes. All strains were ra pidly killed by polymorphonuclear leukocytes but persisted within macrophag es (activated with gamma interferon) to a significantly greater extent (sur vival = 40.5% +/- 17.4%) than did Escherichia coli HB101 (9.3% +/- 0.7%; P = 0.0001). Strains isolated from symptomatic patients were significantly mo re resistant to killing by macrophages (survival = 48.9% +/- 19.5%) than we re strains obtained from food or the environment (survival = 32.1% +/- 10.3 %; P = 0.04). Some strains which had been ingested by macrophages or HEp-2 epithelial cells showed a tendency to reemerge into the tissue culture medi um over a period lasting several hours. This phenomenon, which we termed "e scape," was observed in 14 of 15 strains of clinical origin but in only 3 o f 12 nonclinical isolates (P = 0.001). The capacity of bacteria to escape f rom cells was not directly related to their invasive ability. To determine if escape was due to host cell lysis, we used a variety of techniques, incl uding lactate dehydrogenase release, trypan blue exclusion, and examination of infected cells by light and electron microscopy, to measure cell viabil ity and lysis. These studies established that biotype 1A Y. enterocolitica strains were able to escape from macrophages or epithelial cells without ca using detectable cytolysis, suggesting that escape was achieved by a proces s resembling exocytosis, The observations that biotype 1A Y. enterocolitica strains of clinical origin are significantly more resistant to killing by macrophages and significantly more likely to escape from host cells than ar e strains of nonclinical origin suggest that these properties may account f or the virulence of these bacteria.