ASMicro 2013* Proteolytic processing and protein moonlighting: important but understudied processes in microbial pathogenesis (#8)
Mycoplasmas are host specific pathogens with no known long-term reservoirs outside the host. To survive and proliferate as a species, Mycoplasmas have evolved complex host adherence and immune evasion mechanisms. Mycoplasmas are genome-reduced pathogens that have lost genes encoding for many anabolic pathways including those required for cell wall biosynthesis and various metabolic pathways including a TCA cycle, amino acid and nucleotide biosynthesis. Despite genome reduction, M. hyopneumoniae is a very successful chronic pathogen that inflicts a severe economic burden to swine production. A conceptually unbiased, global proteomic approach of cell surface proteins identified an unprecedented degree of protein processing of cell surface adhesins. Two paralogous gene families encoding large adhesin proteins are highly expressed on the cell surface and play a major role in binding host molecules during colonisation. Processing is an extensive and multi-step process involving different proteases which cleave with varying degrees of efficiency generating an extensive combination of multifunctional adhesin fragments that remain localised to the cell surface. Adhesin fragments bind an array of host molecules and play a role in immune evasion. Our approach has also identified proteins that moonlight on the cell surface as multifunctional proteins. While it has been argued that multifunctionality is an evolutionary by-product of genome reduction, our analyses suggest that proteolytic processing and protein moonlighting play important roles in microbial pathogenesis more broadly.
