Moraxella catarrhalis: from emerging to established pathogen

Abstract

Moraxella catarrhalis (formerly known as Branhamella catarrhalis) has emerged as a significant bacterial pathogen of humans over the past two decades. During this period, microbiological and molecular diagnostic techniques have been developed and improved for M. catarrhalis, allowing the adequate determination and taxonomic positioning of this pathogen. Over the same period, studies have revealed its involvement in respiratory (e.g., sinusitis, otitis media, bronchitis, and pneumonia) and ocular infections in children and in laryngitis, bronchitis, and pneumonia in adults. The development of (molecular) epidemiological tools has enabled the national and international distribution of M. catarrhalis strains to be established, and has allowed the monitoring of nosocomial infections and the dynamics of carriage. Indeed, such monitoring has revealed an increasing number of B-lactamase-positive M. catarrhalis isolates (now well above 90%), underscoring the pathogenic potential of this organism. Although a number of putative M. catarrhalis virulence factors have been identified and described in detail, their relationship to actual bacterial adhesion, invasion, complement resistance, etc. (and ultimately their role in infection and immunity), has been established in a only few cases. In the past 10 years, various animal models for the study of M. catarrhalis pathogenicity have been described, although not all of these models are equally suitable for the study of human infection. Techniques involving the molecular manipulation of M. catarrhalis genes and antigens are also advancing our knowledge of the host response to and pathogenesis of this bacterial species in humans, as well as providing insights into possible vaccine candidates. This review aims to outline our current knowledge of M. catarrhalis, an organism that has evolved from an emerging to a well-established human pathogen.

FIG. 1.

The bacterial species M. catarrhalis and its close relatives. (A) Position of the γ proteobacteria in the prokaryotic kingdom. M. catarrhalis is within this class of organisms. (B) More detailed positioning of M. catarrhalis in the order Pseudomonales. Panel A reprinted from reference with permission of the publisher; the data in panel B are derived from Bergey’s Manual of Determinative Bacteriology, 8th ed. (R. E. Buchanan and N. E. Gibbons, ed.), The Williams & Wilkins Co. Baltimore, Md. (web-accessible version).

FIG. 1.

The bacterial species M. catarrhalis and its close relatives. (A) Position of the γ proteobacteria in the prokaryotic kingdom. M. catarrhalis is within this class of organisms. (B) More detailed positioning of M. catarrhalis in the order Pseudomonales. Panel A reprinted from reference with permission of the publisher; the data in panel B are derived from Bergey’s Manual of Determinative Bacteriology, 8th ed. (R. E. Buchanan and N. E. Gibbons, ed.), The Williams & Wilkins Co. Baltimore, Md. (web-accessible version).

FIG. 2.

Pulsed-field gel electrophoresis of SpeI-digested M. catarrhalis DNA. Twenty nosocomial isolates were analyzed, which resulted in the identification of several clusters of indiscriminate strains. As indicated at the top, isolates 1 and 2 and isolates 17 and 18 are identical, which fits well with the fact that the strains were isolated from the same patients on separate occasions. Strains 5, 10, 11, and 13 were isolated from different patients hospitalized during overlapping time intervals in the same pediatric department. It was concluded that patient-to-patient transmission occurred in this setting.

FIG. 3.

Dendrogram constructed on the basis of RiboPrint pattern types obtained for 13 complement-sensitive and 2 complement-resistant strains of M. catarrhalis (235). Selected were those RiboPrint patterns that are representative of the diverse genogroups that could be identified. The resistant strains appear to be a more homogeneous group (only 2 closely related types encountered among 47 strains) than are the complement-sensitive strains. The tree was constructed in the BioNumerics program developed by Applied Maths (Kortrijk, Belgium). On the basis of Pearson coefficients and unweighted pair group method using arithmetic averages (UPGMA), patterns were normalized using molecular size markers coanalyzed during pattern creation. The 40 to 100 scale above the dendrogram indicates the percent identity between fingerprints compared. The fully automated RiboPrinter has been developed and marketed by Qualicon, a Dupont subsidiary (Warwick, United Kingdom).

FIG. 4.

Schematic structure of the LOS moieties that cover the surface of the M. catarrhalis cells. Three main serotypes, A, B, and C, can be discerned, which differ in the nature of the R group. Abbreviations: D-Galp, 𝒹-galactose phosphate; Kdo, 2-keto-3-deoxyoctonate; GlcpNac, N-acetyllactosamine.

FIG. 5.

Electron micrographs of the binding of human vitronectin to complement-resistant (left) and complement-sensitive (right) strains of M. catarrhalis. Immunogold labeling using antibodies specific for human vitronectin revealed that this protein is effectively bound to the resistant cells whereas the sensitive strain fails to bind a significant quantity of the human matrix protein. Note that the vitronectin protein seems to be attached toward the boundaries of the cellular matrix, which may correlate with the protruded orientation of the vitronectin-binding ubiquitous surface proteins (UspA).