Physiologic cold shock of Moraxella catarrhalisaffects the expression of genes involved in the iron acquisition, serum resistance and immune evasion

Abstract

BackgroundMoraxella catarrhalis, a major nasopharyngeal pathogen of the human respiratory tract, is exposed to rapid downshifts of environmental temperature when humans breathe cold air. It was previously shown that the prevalence of pharyngeal colonization and respiratory tract infections caused by M. catarrhalis are greatest in winter. The aim of this study was to investigate how M. catarrhalis uses the physiologic exposure to cold air to upregulate pivotal survival systems in the pharynx that may contribute to M. catarrhalis virulence.ResultsA 26°C cold shock induces the expression of genes involved in transferrin and lactoferrin acquisition, and enhances binding of these proteins on the surface of M. catarrhalis. Exposure of M. catarrhalis to 26°C upregulates the expression of UspA2, a major outer membrane protein involved in serum resistance, leading to improved binding of vitronectin which neutralizes the lethal effect of human complement. In contrast, cold shock decreases the expression of Hemagglutinin, a major adhesin, which mediates B cell response, and reduces immunoglobulin D-binding on the surface of M. catarrhalis.ConclusionCold shock of M. catarrhalis induces the expression of genes involved in iron acquisition, serum resistance and immune evasion. Thus, cold shock at a physiologically relevant temperature of 26°C induces in M. catarrhalis a complex of adaptive mechanisms that enables the bacterium to target their host cellular receptors or soluble effectors and may contribute to enhanced growth, colonization and virulence.

Expression of the Oligopeptide Permease Operon of Moraxella catarrhalis Is Regulated by Temperature and Nutrient Availability

“…The temperature of the human nasopharynx is variable, with measurements ranging from 37°C to 26°C (2,(17)(18)(19)(20)(21)(22). Temperature has an important impact on virulence factors and transcriptional regulation in M. catarrhalis (23)(24)(25). When cultures were grown at 26°C, the transcript levels of all of the opp genes were significantly elevated compared to transcript levels at 37°C (Fig.…”

“…Exacerbations of COPD related to the acquisition of M. catarrhalis and otitis media increase during the cooler winter months of the year (8,(53)(54)(55). The temperature of the nasopharynx, where M. catarrhalis first colonizes, is 34°C and decreases to 26°C upon exposure to colder temperatures in winter months in temperate climates (17)(18)(19)(20)(21)(22)(23)56). Cold shock increases the expression of the outer membrane protein UspA1, a known virulence factor, which is important for M. catarrhalis binding to host cells as well as immune evasion (23,25).…”

“…The temperature of the nasopharynx, where M. catarrhalis first colonizes, is 34°C and decreases to 26°C upon exposure to colder temperatures in winter months in temperate climates (17)(18)(19)(20)(21)(22)(23)56). Cold shock increases the expression of the outer membrane protein UspA1, a known virulence factor, which is important for M. catarrhalis binding to host cells as well as immune evasion (23,25). Thus, time spent outdoors breathing cooler air alters the temperature of the respiratory tract and could have important effects on bacterial homeostasis and regulation of the Opp system.…”

“…Exposure to cold shock at 26°C has an important impact on virulence factors and transcriptional regulation in M. catarrhalis (23)(24)(25).…”

Identification of an Outer Membrane Lipoprotein Involved in Nasopharyngeal Colonization by Moraxella catarrhalis in an Animal Model

“…Similarly, some changes in the number of heteropolymeric tetranucleotide (AGAT) repeats in the predicted 5= untranslated region (UTR) of the uspA2 gene can adversely affect UspA2 production (26). The effect of a mutation in fur on production of certain M. catarrhalis outer membrane proteins was described by Furano and Campagnari (27), and the ability of low temperature to influence expression of several different M. catarrhalis genes encoding surface proteins was recently reported by Aebi and colleagues (28)(29)(30). The effect of growth under iron-restricted conditions or in the biofilm state on M. catarrhalis gene expression has been studied by means of DNA microarray technology (31), an effort which led to the identification of a number of genes which are highly upregulated in the biofilm state and which, in general, had not been previously described for M. catarrhalis.…”