{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:42:01Z","timestamp":1790757721782,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2001,12,21]],"date-time":"2001-12-21T00:00:00Z","timestamp":1008892800000},"content-version":"vor","delay-in-days":234,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2001,5]]},"abstract":"<jats:p> <jats:italic>Neisseria meningitidis<\/jats:italic> controls the expression of several genes involved in host adaptation by a process known as phase variation. The phase variation frequency of haemoglobin (Hb) receptors among clinical isolates of serogroups A, B and C differed drastically, ranging from \u2248\u200a10<jats:sup>\u22126<\/jats:sup> to 10<jats:sup>\u22122<\/jats:sup>\u2003cfu<jats:sup>\u22121<\/jats:sup>. Frequencies of phase variation are a genetic trait of a particular strain, as two unlinked Hb receptors, <jats:italic>hpuAB<\/jats:italic> and <jats:italic>hmbR<\/jats:italic>, phase varied with similar frequencies within a given isolate. Based on these frequencies, six Neisserial clinical isolates could be grouped into three distinct classes; slow, medium and fast. An increase in phase variation frequency was accompanied by high rates of spontaneous mutation to rifampicin and nalidixic acid resistance in one medium and one fast strain. The remaining three medium strains displayed elevated levels of phase variation without increases in overall mutability, as they possessed low rates of spontaneous mutation to drug resistance. The mismatch repair system of <jats:italic>N.\u00a0meningitidis<\/jats:italic> was found to play an important role in determining the overall mutability of the clinical isolates. Inactivation of mismatch repair in any strain, regardless of its original phenotype, increased mutability to a level seen in the fast strain. Insertional inactivation of <jats:italic>mutS<\/jats:italic> and <jats:italic>mutL<\/jats:italic> in the slow strain led to 500\u2010 and 250\u2010fold increases in <jats:italic>hmbR<\/jats:italic> switching frequency respectively. Concurrently, the frequency of spontaneous point mutations of <jats:italic>mutS<\/jats:italic> and <jats:italic>mutL<\/jats:italic> mutants from the slow strain was increased 20\u2010 to 30\u2010fold to the level seen in the high strain. The status of Dam methylation did not correlate with either the phase variation frequency of Hb receptors or the general mutability of Neisserial strains. Analysis of an expanded set of isolates identified defects in mismatch repair as the genetic basis for strains displaying both the fast Hb switching and high mutation rate phenotypes. In conclusion, elevated frequencies of phase variation were accompanied by increased overall mutability in some <jats:italic>N. meningitidis<\/jats:italic> isolates including strains shown to be mismatch repair defective. Other isolates have evolved mechanisms that seem to affect only the switching frequency of phase\u2010variable genes without an accompanied increased accumulation of spontaneous mutations.<\/jats:p>","DOI":"10.1046\/j.1365-2958.2001.02408.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T11:37:52Z","timestamp":1047469072000},"page":"645-655","source":"Crossref","is-referenced-by-count":117,"title":["Mismatch repair and the regulation of phase variation in <i>Neisseria meningitidis<\/i>"],"prefix":"10.1111","volume":"40","author":[{"given":"A. 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