Abstract
Moraxella catarrhalis is a common human respiratory tract pathogen. Its virulence factors associated with whole bacteria or outer membrane vesicles (OMVs) aid infection, colonization and may induce specific antibodies. To investigate pathogen-host interactions, we applied integrated bioinformatic and immunoproteomic (2D-electrophoresis, immunoblotting, LC-MS/MS) approaches. We showed that OMV proteins engaged exclusively in complement evasion and colonization strategies, but not those involved in iron transport and metabolism, are major targets for cross-reacting antibodies produced against phylogenetically divergent M. catarrhalis strains. The analysis of 31 complete genomes of M. catarrhalis and other Moraxella revealed that OMV protein-coding genes belong to 64 orthologous groups, five of which are restricted to M. catarrhalis. This species showed a two-fold increase in the number of OMV protein-coding genes relative to its ancestors and animal-pathogenic Moraxella. The appearance of specific OMV factors and the increase in OMV-associated virulence proteins during M. catarrhalis evolution is an interesting example of pathogen adaptation to optimize colonization. This precisely targeted cross-reactive immunity against M. catarrhalis may be an important strategy of host defences to counteract this phenomenon. We demonstrate that cross-reactivity is closely associated with the anti-virulent antibody repertoire which we have linked with adaptation of this pathogen to the host.
Highlights
Moraxella catarrhalis is an important human-restricted pathogen responsible for sinusitis and otitis media in children as well as infections of the lower respiratory tract, causing exacerbation of chronic obstructive pulmonary disease in adults[1,2]
To investigate the nature and basis of our previous observations and define the specific profile of outer membrane proteins (OMPs) targeted by cross-reactive antibodies, we performed an immunoproteomic analysis of outer membrane vesicles (OMVs) from two clinical strains of M. catarrhalis (Mc6 and Mc8) which differ in phenotypic properties, lipooligosaccharide (LOS) type, source of origin[26] and belong to distant phylogenetic lineages
Our comprehensive computational analyses of 31 complete Moraxella genomes and three representatives of Acinetobacter showed that OMV proteins identified in M. catarrhalis are organized in 64 orthologous groups and involved in various functions, especially those related to cell membrane and inorganic ion transport
Summary
Moraxella catarrhalis is an important human-restricted pathogen responsible for sinusitis and otitis media in children as well as infections of the lower respiratory tract, causing exacerbation of chronic obstructive pulmonary disease in adults[1,2]. The most important virulence strategies involve: (1) evasion of complement-mediated killing mainly via interference with regulatory proteins[13,14,15]; (2) polyclonal, non-specific B cell activation and redirecting of adaptive immunity[16]; (3) hiding inside lymphoid tissue, which is the main reservoir facilitating the host invasion[17]; (4) formation of biofilm[18,19]; and (5) participation in protease-antiprotease imbalance[20] Some of these strategies can be driven in part by the release of outer membrane vesicles (OMVs), which contain several virulence factors facilitating the delivery of periplasmic and outer membrane components to the host[14,21]. We performed extensive bioinformatics analyses of OMV proteins including four newly sequenced and all previously published Moraxella complete genomes to study features of these proteins from a genomic and evolutionary perspective with particular emphasis on their role in virulence
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