Project 456311

The transfer of antibiotic resistance genes causes increasing resistance of pathogenic bacteria to treatments. This causes increasing cost to our health care system and leads to increased mortality and morbidity of patients infected with bacteria that resist antibiotic treatments. There are widespread concerns about this process that may ultimately lead to the evolution of so-called "superbugs" that can not be treated with antibiotics. Bacterial conjugation is a major contributing factor to this development since it leads to the transfer of plasmids between bacteria and these DNA elements often carry antibiotic resistance genes. It is therefore necessary to better understand the molecular details of this process to interfere with bacterial conjugation and to reduce the spread of antibiotic resistance genes. We here propose to study the structure and function of bacterial surface-exposed pilus structures that initiate conjugation at unprecedented resolution. We will use approaches of structural biology, biochemistry and bacterial genetics. Based on the information obtained from this work it may be possible to design molecules that reduce conjugation between pathogenic bacteria and thereby the spread of antibiotic resistance genes.