BRO beta-lactamase alleles, antibiotic resistance and a test of the BRO-1 selective replacement hypothesis in Moraxella catarrhalis.
OBJECTIVE
The hypothesis that BRO-1 selectively replaced the BRO-2 isoform of the Moraxella catarrhalis BRO beta-lactamase was tested by examining the temporal distribution, antibiotic resistance and epidemiological characteristics of isolates from a long-term collection at a single locale.


METHODS
A rapid, one-step PCR assay conducted on 354 isolates spanning 1984-1994 distinguished bro alleles in over 97% of the beta-lactamase-producing isolates. Probes of dot blots were used to distinguish PCR failure from non-beta-lactamase-mediated penicillin resistance.


RESULTS
BRO-2 isolates comprised 0-10% of the population per year with no evidence of a decline over time. All beta-lactamase producers exceeded the clinical threshold for penicillin resistance. Bimodality of penicillin MICs for beta-lactamase producers was caused by variation within BRO-1 rather than differences between BRO-1 and BRO-2. Non-beta-lactamase factors also confer resistance to penicillin and may contribute to the BRO-1 bimodality. The 13 BRO-2 isolates were associated with diverse genotypes within which there was evidence of epidemiologically linked clusters. The exclusive association of BRO-2 with four unrelated genotypes suggested maintenance of BRO-2 by recurrent mutation or horizontal exchange.


CONCLUSIONS
The relative rarity of BRO-2 throughout the study, the absence of a declining temporal trend, and genetic diversity within BRO-2 all failed to support the hypothesis that BRO-2 was more common in the past and has been selectively replaced by BRO-1.
Levy
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Departments of Biological Sciences, Box 70703 and Internal Medicine, Box 70622, East Tennessee State University, Johnson City, TN 37614, USA. levyf@etsu.edu
Walker
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ES
D000483:Alleles; D024881:Drug Resistance, Bacterial; D005798:Genes, Bacterial / Q000235:genetics; D016905:Gram-Negative Bacterial Infections / Q000453:epidemiology / Q000382:microbiology; D001936:Moraxella catarrhalis / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D010403:Penicillin Resistance; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001618:beta-Lactamases / Q000235:genetics*
C408134:BRO beta-lactamase; D001618:beta-Lactamases