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Sugar code and hygiene in the fight against multi-resistant pathogens

Horizontal gene transfer between bacteria is a major reason for the spread of bacterial antibiotic resistance. It is the transfer of bacterial DNA from one bacterium to another, even distantly related species, by bacteriophages, viruses that infect bacteria. Microbiologists from the University of Tübingen are investigating these mechanisms with the aim of finding new strategies that would effectively combat bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), which is a troublesome bacterial strain in hospitals. In addition, the researchers are calling for more effective hygiene measures and are involved in the in-depth investigation of bacterial ecology.

False-colour representation clearly reveals the presence of a biofilm consisting of a substance matrix (yellow) produced by Staphylococcus aureus bacteria (grey). © Peschel, University of Tübingen

Scientists and clinicians from the University of Tübingen have joined forces in the Interfaculty Institute for Microbiology and Infection Medicine (IMIT) in order to increase knowledge about bacteria and develop strategies for their more effective destruction. “Actually, the establishment of the interdisciplinary institute and pooling the infectious disease knowledge that existed at the university in the fields of biology and medicine was only a small step. However, given the lack of confidence that unfortunately widely prevails between medical doctors and biologists, establishing the IMIT was something special. We are the first and only institute of this kind in Germany,” says Prof. Dr. Andreas Peschel, head of the IMIT’s department of cellular and molecular microbiology.

The IMIT researchers’ latest findings on the spread of bacterial resistance emphasize the importance of interdisciplinary cooperation. Peschel and his team reported in a paper in 2013 that the presence of specific sugar structures on the surface of the bacterial cells determine whether or not bacteriophages, i.e. viruses that infect and replicate within bacteria, recognize bacterial cells. 

When the bacteriophages have identified a bacterial cell as host, they enter it and replicate massively. The bacteriophages carry bacterial DNA which they would have taken up in their previous host cell during propagation and transfer it to the newly infected bacterial cell. This process is known as horizontal gene transfer and leads to the transfer of bacterial DNA from one bacterial strain to another. If, for example, the foreign genetic material contains an antibiotic resistance gene, the newly infected bacterial strain might also become resistant to this particular antibiotic. DNA can also be transferred between bacteria of two different species; it just requires the two species to have similar sugar structures on their cell surface. 

The pivotal role of horizontal gene transfer

Peschel and his team are exploring the effect of horizontal gene transfer in Staphylococcus aureus, a greatly feared pathogen in hospitals as S. aureus strains are developing resistances against many standard antibiotics. The number of multidrug-resistant S. aureus strains is increasing. The process of horizontal gene transfer enables the researchers’ laboratory strains to exchange genetic material with other human pathogens, such as Listeria monocytogenes, for example. They are able to do this because Listeria bacteria have very similar teichoic acids on their surface to S. aureus. These sugar structures are used by bacteriophages to recognize which bacteria to infect. Peschel and his group of researchers have also been able to show that enterococci, which have different sugar structures to S. aureus, do not exchange DNA with S. aureus.

Electron microscope image showing bacteriophages that infect and replicate within Staphylococcus aureus strains. © York Stierhoff, University of Tübingen

Exploiting the enemies’ strategies 

Peschel also believes that it is worth copying the strategy of bacteriophages: bacteriophages that have entered a bacterial host cell propagate and reprogramme the bacterial metabolism. The bacteria then produce enzymes that dissolve the bacterial envelope, thereby initiating their own death. Such enzymes have the potential to be used for medical therapy. “Around 40 percent of all humans carry Staphylococcus aureus bacteria in their noses. If we could apply such enzymes to the nose, then we would be able to free the nose from S. aureus. This would be a simple method to effectively prevent the spread of S. aureus, and in particular MRSA.” Such new concepts are necessary in order to free the nose from bacteria that are no longer susceptible to standard antibiotics.

Peschel believes that the increasing resistance of MRSA to standard antibiotics is due to the lack of effective hygienic measures, which promotes the spread of MRSA. “When a patient is undergoing a major operation, good hospitals will always test for the presence of staphylococci and if necessary initiate decolonization measures. This takes a few days and naturally costs money, money that some hospitals would rather not spend.” However, not spending money on simple MRSA tests can potentially backfire and result in costly processes having to be put in place to combat resistances and infections. Peschel also believes that it is necessary to take action, because S. aureus infections can lead to fatal sepsis.

This is why he is calling for more effective measures for protecting hospitalized patients from MRSA infection. “Hygiene and infectiology are often very unpopular topics as hospitals often believe them to be costly.” Peschel believes that the reporting of MRSA infections leads to a reduction in the high number of infections and he is calling for MRSA infections to be published in Germany, as they are elsewhere. “In Great Britain, all hospitals are required to report the number of MRSA infections. When this procedure became mandatory several years ago, there was an outcry and hospitals with high MRSA rates found it difficult to recruit patients. However, since reporting began, the UK has seen a significant year on year reduction in MRSA infections. This is why we consider it irresponsible to have no reporting obligation in Germany. We are working with institutions like the DZIF and ministries to change this,” says Peschel. DZIF is the acronym for German Centre for Infection Research, which is an affiliation of research institutes located at seven sites distributed throughout Germany including Tübingen.

Preventing hygiene mistakes

“Other Staphylococcus species can also lead to infections and develop resistances, albeit in a weaker form,” says Peschel. “Staphylococcus epidermidis bacteria are part of the normal human skin flora, but they not lead to as dramatic infections as S. aureus. S. epidermidis infections might for example occur in catheterised patients due to ineffective disinfection of the relevant skin area. The bacteria can thus colonize the intravenous catheters and lead to infection. “Although S. epidermidis infections can be prevented by proper hygiene measures, they unfortunately still occur.”

Although not all Staphylococcus species are as pathogenic as S. aureus, this might rapidly change due to horizontal gene transfer which leads to the constant exchange and expansion of the bacterial gene pool and also to the evolution of new bacterial species. Future development is difficult to assess, partly because very little is known about the bacterial ecology. “80 percent of all severe infections are caused by endogenous bacteria. If they get the chance to enter tissue, they do so, and friends become enemies. If we could better understand these processes, I am convinced that we would be able to put in place more effective preventive measures, especially for high-risk patients,” concluded Peschel.

Further information:

Prof. Dr. Andreas Peschel
Interfaculty Institute for Microbiology and Infection Medicine (IMIT)
University of Tübingen
Elfriede-Aulhorn-Str. 6
72076 Tübingen
Tel.: +49 (0)7071 29-81515
E-mail: Andreas.Peschel(at)med.uni-tuebingen.de

Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/sugar-code-and-hygiene-in-the-fight-against-multi-resistant-pathogens