Production of BRO β-Lactamases and Resistance to Complement in European Moraxella catarrhalis Isolates

Abstract

Of the 419 Moraxella catarrhalis isolates collected during the 1997-1999 European SENTRY surveillance study, 385 (92%) were ␤-lactamase positive. Twenty-two (5.7%) produced BRO-2 ␤-lactamase. Twenty-one new mutations were found in the putative promoter region of the bro genes. Nineteen percent of all isolates tested were complement sensitive. Resistance to ␤-lactams is not linked to the phylogenetic lineages associated with susceptibility to complement.Moraxella catarrhalis was long considered a harmless commensal of the respiratory tract and uniformly susceptible to penicillins. In recent years, however, its pathogenic potential has come to light (9,20,27). The production of a new ␤-lactamase enzyme, designated BRO (from Branhamella and Moraxella), by this bacterium was an event that occurred virtually simultaneously around the world (9,13,19,20). Two distinct BRO ␤-lactamase enzymes, namely, BRO-1 and BRO-2, have since been found in strains of M. catarrhalis. These enzymes are identical in substrate and inhibition profile but differ by a single amino acid (2-5). The increased level of resistance conferred by BRO-1 compared to BRO-2 appears to be related to the relative amount of each enzyme produced by the strains (5). This difference in production may be the result of differences in the promoter strength of the two genes. Bootsma et al. (5) reported a 21-bp deletion in the promoter region of the ␤-lactamase gene from a BRO-2-producing strain. In addition, Richter et al. (22) suggested that additional mutations or deletions or insertions in the promoter sequence might explain the variations seen in antibiotic susceptibilities within the populations of BRO-1-and BRO-2-producing M. catarrhalis isolates.The first goal of this study, therefore, was to characterize the BRO ␤-lactamases and their putative promoter regions in the European M. catarrhalis isolates collected between 1997 and 1999 during the European SENTRY surveillance study. The relative percentages of the two enzyme types were also determined.Besides protecting the bacteria against ␤-lactam antibiotics, ␤-lactamase can also have indirect pathogenic effects. For example, it can block the antibiotic treatment of concomitant infections with more dangerous pathogens (e.g., pneumococci), as experimentally confirmed by . This, together with the discovery of M. catarrhalis as a pathogen in its own right, has aroused scientific interest in other possible virulence factors. One of these virulence factors is the ability of M. catarrhalis to resist the action of complement (9,12,17,20,(24)(25)(26). Based on molecular typing data, i.e., pulsed-field gel electrophoresis and PCR-restriction fragment length polymorphism analysis, it has been suggested that complement-resistant M. catarrhalis isolates form a genetically distinct lineage with a different pathogenic potential within the species (3,26,28). The second aim of this study, therefore, was to determine the percentage of complement-resistant M. catarrhalis isolates in the recent SENTRY surveillance study and t...

The UspA2 Protein of Moraxella catarrhalis Is Directly Involved in the Expression of Serum Resistance

“…The fact that some strains of M. catarrhalis can resist serum killing was first described some 20 years ago by Winn and Morse (reviewed in references 10 and 50), and several recent studies indicate that the vast majority of M. catarrhalis isolates are resistant to serum killing (13,34,45). The identity of the gene product(s) responsible for this phenotype has been the subject of much research interest over the past decade, and it was first suggested by Verduin et al (54) that a proteinaceous substance on the surface of M. catarrhalis was responsible for complement resistance.…”

“…First observed about 20 years ago (reviewed in references 10 and 50), the occurrence of the serum-resistant phenotype has been documented in many subsequent studies of M. catarrhalis isolates (10,13,25,34,45,50,59). The hypothesis that serum resistance might be a virulence factor for M. catarrhalis stemmed from observations that the incidence of complement-resistant M. catarrhalis strains was higher in samples isolated from ill patients (i.e., adults with lower respiratory tract infections) than in samples from healthy adults or children (20,25).…”

Molecular Characterization of Fluoroquinolone-Resistant Moraxella catarrhalis Variants Generated In Vitro by Stepwise Selection

“…M. catarrhalis is known to be resistant to penicillin and first-generation cephalosporins, owing to its ability to produce BRO ␤-lactamase; however, it typically remains susceptible to other antibiotics, including fluoroquinolones (2)(3)(4). Fluoroquinolones act primarily by inhibiting DNA gyrase and topoisomerase IV.…”

Hag Mediates Adherence ofMoraxella catarrhalisto Ciliated Human Airway Cells

“…catarrhalis infections are a matter of concern due to high carriage rates in children, the lack of a preventative vaccine, and the rapid emergence of antibiotic resistance in clinical isolates. Virtually all M. catarrhalis strains are resistant to ␤-lactams (34,47,48,50,53,65,81,84). The genes specifying this resistance appear to be gram positive in origin (14, 15), suggesting that the organism could acquire genes conferring resistance to other antibiotics via horizontal transfer.…”