Hacking the Bacterial Social Network

structure of protein complex CdiA-Cdil-EF-Tu
Scientists have determined the molecular structure of this protein complex—an insight that could lead to new biomedical strategies for overcoming pathogenic bacteria that cause infectious diseases. This representation shows the neutralized complex of the CdiA toxin (purple and beige) with the CdiI immunity protein (orange and pink) and the elongation factor (EF)–Tu (grey and green). [Karolina Michalska, Argonne National Laboratory]
Scientists have determined the molecular structures of a highly specialized set of proteins that a strain of Escherichia coli bacteria use to communicate and defend their turf. Ironically, loads of bacteria cover the devices humans use to communicate—even more than on toilet seats, according to one study. Bacteria appear to have their own form of social network that allows these single-cell creatures to attract and repel one another. This insight stems from new research that could lead to new biomedical strategies for overcoming pathogenic bacteria that cause infectious diseases such as pneumonia and food-borne illnesses.

The work builds on the 2005 discovery that the bacteria produce toxic proteins, which they can transfer to their neighbors through direct contact to either kill or control them, possibly to gain better access to nutrients in densely populated microbial communities through a process called contact-dependent growth inhibition (CDI). Learning how the bacteria interact and communicate is helping to resolve the possibly different activities of the toxins, which “may affect different bacteria differently.” Found in soil and gut bacteria, as well as in human pathogens, some of these toxins of CDI systems are present, for example, in Pseudomonas aeruginosa, which is involved in lung disease.

The team obtained the molecular structures of proteins that belong to a three-part system of the NC101 strain of E. coli, which consists of the CDI toxin, its immunity protein, and its elongation factor (EF). The latter, known as EF-Tu, is a protein that plays a key role in protein synthesis. Knowing the protein structures of all three parts helps scientists understand their function. Discovery of the immunity protein has led scientists to suspect that the system’s purpose  includes competition and signaling (intracommunication), as well as killing and controlling other bacteria. Actually, only a few molecules of the toxin “get into the neighboring cell,” so perhaps the toxin is “not meant to kill, but rather to control and communicate.” It can act on the transfer ribonucleic acid (tRNA) only under highly specific circumstances, and it is the first case seen where the EF is “needed for the toxin to function.” Researchers used high-bright X-rays to characterize, or identify, biological proteins and inspect chemical processes at the nanoscale level (i.e., one billionth of a meter).

Michalska, K., et al. “Structure of a Novel Antibacterial Toxin That Exploits Elongation Factor Tu to Cleave Specific Transfer RNAs.” Nucleic Acids Res. 45(17), 10306–10320 (2017). [DOI:10.1093/nar/gkx700].

Instruments and Facilities Used: Advanced Photon Source 19-ID beamline and Advanced Protein Characterization Facility at Argonne National Laboratory.