New agents join the fight against antibiotic-resistant bacteria

With her PhD project, Line Hein-Kristensen from the National Food Institute, Technical University of Denmark has, in collaboration with the Faculty of Health and Medical Sciences, University of Copenhagen, and DTU Systems Biology, demonstrated that a new class of chemically produced antimicrobial agents could become a future infection treatment alternative. These findings are another advance for researchers in the fight against antibiotic-resistant bacteria.

Antimicrobial peptides providing the platform Line Hein-Kristensen worked with a new class of antimicrobial agents, the so-called antimicrobial peptides. Antimicrobial peptides are part of the immune system in all life forms, including humans, and constitute the first line of defence against pathogenic organisms entering the body, e.g. via the food that we eat.

Antimicrobial peptides are special in that they act differently to conventional antibiotics and may thus be active against the very bacteria that are resistant to conventional antibiotics. These also include multiresistant bacteria -- for example MRSA and ESBL against which we now have only a limited arsenal of treatment options.

Synthetic compound emulating nature Novel chemical methods have now made it possible to emulate the structure of natural antimicrobial peptides and thus also to develop many novel synthetic variants. Line Hein-Kristensen's PhD project focuses specifically on a series of synthetic compounds that have been designed, synthetised and characterised the Faculty of Health and Medical Sciences, University of Copenhagen.

The findings of her research show that the degree of antimicrobial activity against a range of food-borne and nosocomial (hospital-acquired) pathogenic bacteria depends on the chemical structure of custom-designed compounds. The research also shows that the synthetic antimicrobial peptides kill the bacteria by disrupting the bacterial cell membrane

With long-term exposure, resistance to the synthetic antimicrobial peptides may develop, but there are no current signs of cross-resistance, i.e. resistance to several different compounds with different chemical structures. This means that if bacteria become resistant to some of these compounds, other antimicrobial peptides could potentially be used for treating bacterial infections.

"If we are able to optimise the chemical structure of the synthetic compounds, we can limit the development of resistant bacteria," says Line Hein-Kristensen from the National Food Institute about the findings presented in her PhD thesis.

"We hope that one day antimicrobial peptides can become a viable alternative to conventional antibiotics," Line Hein-Kristensen adds.

Background info

Antimicrobial resistance When bacteria are exposed to antibiotics, they protect themselves by developing resistance in order to survive. The resistant bacteria have changed their hereditary material -- their genes.

ESBL Due to the use of broad-spectrum antibiotics, in particular cephalosporins, the bacteria become resistant to this type of antimicrobial agent. What is special about cephalosporin-resistance is that the bacteria also become resistant to almost all types of penicillin.

The enzymes responsible for cephalosporin resistance are called ESBL (Extended-Spectrum Beta-Lactamases or cephalosporinases). Cefalosporin-resistant bacteria, such as E. coli, Salmonella and Klebsiella are thus called ESBL-producing bacteria or simply ESBL bacteria

Researches find the same types of ESBL genes in both humans and meat.

MRSA MRSA is short for Methicillin-resistant Staphylococcus Aureus.

Staphylococci are bacteria found in humans, animals and in our surrounding environment. Staphylococcus aureus is part of the normal nasal and skin flora in approx. 50% of the population. Staphylococcus aureus can cause a wide range of infections, from superficial wounds and abscesses to serious infections such as Osteitis and Endocarditis. In hospitals, staphylococcus aureus is the most frequent cause of post-surgery infections.

The gene which primarily causes the resistance is called mecA. This makes the bacteria resistant to all so-called beta-lactam antibiotics, including penicillins and the broad-spectrum antimicrobial agents cephalosporines.

Researches are finding the same types of MRSA genes in both humans and a number of animals, including pigs and cows.

More information on Hein-Kristensen's PhD thesis: Spectrum and activity of novel antimicrobial peptidomimetics (PDF).