Moraxella catarrhalis phase-variable loci show differences in expression during conditions relevant to disease

Abstract

Moraxella catarrhalis is a human-adapted, opportunistic bacterial pathogen of the respiratory mucosa. Although asymptomatic colonization of the nasopharynx is common, M. catarrhalis can ascend into the middle ear, where it is a prevalent causative agent of otitis media in children, or enter the lower respiratory tract, where it is associated with acute exacerbations of chronic obstructive pulmonary disease in adults. Phase variation is the high frequency, random, reversible switching of gene expression that allows bacteria to adapt to different host microenvironments and evade host defences, and is most commonly mediated by simple DNA sequence repeats. Bioinformatic analysis of five closed M. catarrhalis genomes identified 17 unique simple DNA sequence repeat tracts that were variable between strains, indicating the potential to mediate phase variable expression of the associated genes. Assays designed to assess simple sequence repeat variation under conditions mimicking host infection demonstrated that phase variation of uspA1 (ubiquitous surface protein A1) from high to low expression occurs over 72 hours of biofilm passage, while phase variation of uspA2 (ubiquitous surface protein A2) to high expression variants occurs during repeated exposure to human serum, as measured by mRNA levels. We also identify and confirm the variable expression of two novel phase variable genes encoding a Type III DNA methyltransferase (modO), and a conserved hypothetical permease (MC25239_RS00020). These data reveal the repertoire of phase variable genes mediated by simple sequence repeats in M. catarrhalis and demonstrate that modulation of expression under conditions mimicking human infection is attributed to changes in simple sequence repeat length.

Supercritical CO2 assisted extraction of essential oil and naringin from Citrus grandis peel: in vitro antimicrobial activity and docking study

“…Meanwhile, the essential oils containing an abundant content of D-limonene were rarely used for testing against strain M. c, which may cause infections of the eye, middle ear, and central nervous system of humans. 48 3.1.3. In silico docking study of D-limonene.…”

Gene Expression Regulation in Airway Pathogens: Importance for Otitis Media

“…Specifically, in response to host immune defense-derived nitrosative and oxidative stress, Mcat with "ON" variant of modM3 upregulated the expression of genes narX/narL, and a predicted AhpC/TSA family peroxiredoxin RS03200, respectively (Blakeway et al, 2019). Additionally, in a recent study aiming to reveal the correlation between serum resistance and phase variation, Mcat strains that survived in human serum have higher mRNA levels of uspA2 whereas mid/hag and uspA1 showed reduced expression over a longer time of exposure to the human serum (Tan et al, 2020). Under this selection pressure, variable SSR tract lengths that regulate transcription hence phase variation in uspA1, uspA2 and mid/hag is likely to occur.…”

“…Under this selection pressure, variable SSR tract lengths that regulate transcription hence phase variation in uspA1, uspA2 and mid/hag is likely to occur. Antigenic variation of outer membrane proteins is another strategy of Mcat for host immune evasion (Murphy et al, 2019;Tan et al, 2020).…”