Multitasking Bacterial Moonlighting Proteins in Bacterial Virulence and Infectious Disease

Abstract

Men may not be able to multitask, but it seems that proteins can. Although the one gene-one protein-one function hypothesis is well ingrained in the Central Dogma, it has become clear during the past decade that many proteins have one or more unique functions in addition to their primary biological action. These proteins perform multiple independent and often unrelated roles without partitioning these functions into different domains of the protein. This ability of proteins to exhibit more than one function is referred to as protein moonlighting, in analogy to moonlighting people who have multiple jobs. Many well known proteins are now known to moonlight, for example, metabolic enzymes, which in addition to their catalytic function are involved in fully unrelated processes such as autophagy, protein transport or DNA maintenance. Additionally, a growing number of bacterial species are also being found to express moonlighting proteins and the moonlighting activities of such proteins can contribute to bacterial virulence behaviour. This review recapitulates the current knowledge of moonlighting proteins and highlights the multiple roles displayed by a range of bacterial proteins. Also discussed is the role moonlighting activity plays in the virulence characteristics of a number of important human pathogens, including Streptococcus pyogenes, Streptococcus pneumoniae, Helicobacter pylori, and Mycobacterium tuberculosis. The medical relevance and noteworthy implications for fundamental biomedical research are also reviewed. It appears that only the tip of the bacterial moonlighting iceberg has been seen and in the near future we will see numerous new discoveries of bacterial moonlighting proteins with roles in bacterial virulence. Moonlighting is a phenomenon that illustrates nature's ingenuity. It is a source of stimulation that should remind scientists to always keep the unexpected in mind, even on well-known ground.