1887

Abstract

Hypermutable bacterial pathogens exist at surprisingly high prevalence and benefit bacterial populations by promoting adaptation to selective environments, including resistance to antibiotics. Five hundred isolates were screened for an increased frequency of mutation to resistance to rifampicin, nalidixic acid and spectinomycin: of the 14 hypermutable isolates identified, 12 were isolated from cystic fibrosis (CF) sputum. Analysis by enterobacterial repetitive intergenic consensus (ERIC)-PCR and ribotyping identified eight distinct genetic fingerprints. The hypermutable phenotype of seven of the eight unique isolates was associated with polymorphisms in conserved sites of . Four of the mutant alleles were cloned and failed to complement the mutator phenotype of a  : : TSTE mutant of strain Rd KW20. Antibiotic susceptibility testing of the hypermutators identified one -lactamase-negative ampicillin-resistant (BLNAR) isolate with two isolates producing -lactamase. Six isolates from the same patient with CF, with the same genetic fingerprint, were clonal by multilocus sequence typing (MLST). In this clone, there was an evolution to higher MIC values for the antibiotics administered to the patient during the period in which the strains were isolated. Hypermutable with mutations in are prevalent, particularly in the CF lung environment, and may be selected for and maintained by antibiotic pressure.

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2004-09-01
2019-11-13
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vol. , part 9, pp. 2947-2958

Predicted amino acid sequences translated from DNA sequences of , aligned using CLUSTAL W( http://clustalw.genome.ad.jp/) are presented in an Acrobat PDF file.

For comparison to a sequence with previous structure and function studies, the K12-MG1655 was included and is indicated by K12 (sequence from TIGR). The R652 (Rd KW20) sequence is indicated on the top line and each sequence below that matches the amino acid in R652 is indicated by a period (.); dashes (-) indicate the absence of matching amino acids in the sequence. The CLUSTALprogram produces a consensus sequence from all of the input sequences and attempts to indicate the strength of conservation when an amino acid substitution occurs: when all sequences have identical amino acids in one position, a star (*) is indicated in the consensus line; when an amino acid substitution occurs in one or more sequences with a relatively strong conservation, a colon (:) is indicated; when a substitution occurs with a relatively weak conservation, a period (.) is indicated; when a substitution occurs with no conservation, a blank is indicated. These strengths of conservation are based on positively scoring groups in the Gonnet Pam250 matrix.

Assistance in the use and interpretation of CLUSTALprograms can be found at http://www-igbmc.u-strasbg.fr/BioInfo/ClustalX/Top.html.



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