These systems are present in both Gram-negative and Gram-positive bacteria. They form multi-megaDalton machines embedded in membranes and are responsible for the secretion of both proteins and nucleic acid substrates. They play major roles in pathogenicity of, for example, Helicobacter pylori, the causative agent of ulcers. They also mediate transfer of plasmid DNAs during conjugation, a process that leads to the spread of antibiotics resistance genes. T4S systems are composed of 12 proteins named VirB1-11 and VirD4 that assemble into a formidable nanomachine of more than 3 megaDalton in size and spanning the two membranes of Gram-negative bacteria.