KARYOTYPE INSTABILITY IN CRYPTOCOCCUS-NEOFORMANS INFECTION

The electrophoretic karyotypes of 32 clinical and 3 environmental Cryp tococcus neoformans isolates from New York City were studied by contou r clamped homogeneous electrophoresis. There was extensive variation a mong the electrophoretic karyotypes of isolates from different patient s. Sequential C. neoformans isolates from patients with chronic or rel apsing infection had very similar karyotypes. However, minor differenc es in electrophoretic karyotypes were detected among sequential isolat es from 50% of the patients studied, suggesting the occurrence of chro mosomal rearrangements or deletions in vivo, This hypothesis was teste d by infecting mice, recovering isolates from mouse organs, and compar ing the electrophoretic karyotypes before and after passage, Three cli nical and three environmental strains were studied before and after pa ssage in mice. Karyotype differences were detected after mouse passage for one clinical and two environmental strains, Our results indicate (i) extensive karyotype variation among isolates from a small geograph ic region, (ii) a high frequency of electrophoretic karyotype differen ces among sequential isolates from individual patients, and (iii) the occurrence of electrophoretic karyotype changes during experimental in fection of mice, The implications of these observations are discussed.