Project-ID: LS14-006
Project start: 01. March 2016
Runtime: 36 months / finished
Funding amount: € 267.740,00

Brief summary

Hospital-acquired-infections caused by antibiotic resistant pathogens is a global concern to public health. Even the Obama Administration has recently acknowledged the need for innovative research to slow down the public health threat of antibiotic resistant bacteria with a National Strategy for Combating Antibiotic Resistant Bacteria (CARB). The increasing prevalence of antibiotic resistant and multi-drug-resistant pathogens has been shown to considerably expand the burden of disease, despite numerous infection control measures and modern hospital epidemiology. Thus, antimicrobial resistance in microbes is considered to be one of the major threats in medicine and public health worldwide. The horizontal spread of antimicrobial resistance between bacteria is a critical step in the development of resistance during therapy, the dissemination of resistance between different bacterial species, the acquisition of resistance from environmental sources, and the evolution of the bacterial host. An understanding of the mechanisms of horizontal transfer of antimicrobial resistance genes between microorganisms inside and outside of the host is essential to finding strategies to combat their spread. Current knowledge is that the transfer of resistance factors is largely due to conjugative plasmids or transposons and only to a minor extent transduction via bacteriophages. However, based on whole genome sequencing it has been hypothesized that the latter mechanism might play a substantially more important role in the transfer of antimicrobial resistance than is currently accepted. Recently we were able to show that phage transduction is of primary importance in the acquisition of therapeutically important resistance genes in Escherichia coli found on food. We reported that chicken meat carries a number of coli-phages capable of transferring antimicrobial resistance. High numbers of randomly tested phages were able to transduce one or more antimicrobial resistances. Phage transduction of specific resistance elements appears to be widely distributed. This mechanism of transfer may explain unanswered questions regarding the emergence and spread of antimicrobial resistant pathogens. In this proposal we hypothesize that transduction of antibiotic resistance by phages in the medical environment takes place and has important consequences for human health. Thus, the development of new control strategies to cope with phage persistence and transduction need to be found. Thus, we propose to investigate the significance of transduction in the medical environment for hospital-associated pathogens causing major problems by means of antibiotic resistance like Escherichia coli and Staphylococcus aureus. We will isolate and characterize antimicrobial resistance transferring phages, clarify the mechanisms of transfer, analyse the therapeutic importance and finally explore the transduced bacterial host for phage transmission and virulence.

Keywords:
Molecular microbiology, antibiotic resistance, hygiene