Colicin-Mediated Transport of DNA through the Iron Transporter FepA
Ruth Cohen-Khait, Ameya Harmalkar, Phuong Pham, Melissa N. Webby, Nicholas G. Housden, Emma Elliston, Jonathan T. S. Hopper, Shabaz Mohammed, Carol V. Robinson, Jeffrey J. Gray, Colin Kleanthous
Abstract
Decades of excessive use of readily available antibiotics has generated a global problem of antibiotic resistance and, hence, an urgent need for novel antibiotic solutions. Bacteriocins are protein-based antibiotics produced by bacteria to eliminate closely related competing bacterial strains. Bacteriocin toxins have evolved to bypass the complex cell envelope in order to kill bacterial cells. Here, we uncover the cellular penetration mechanism of a well-known but poorly understood bacteriocin called colicin B that is active against Escherichia coli. Moreover, we demonstrate that the colicin B-import pathway can be exploited to deliver conjugated DNA cargo into bacterial cells. Our work leads to a better understanding of the way bacteriocins, as potential alternative antibiotics, execute their mode of action as well as highlighting how they might even be exploited in the genomic manipulation of Gram-negative bacteria.