When bacteria exchange resistance genes with each other

Nr. 198 • 21. Dezember 2023 - Deutsch

Bacteria that are resistant to broad-spectrum antibiotics from the carbapenem group are increasingly posing major problems for healthcare systems worldwide. They can cause serious infections and outbreaks for which there are very limited or no treatment options. The bacteria benefit from the fact that they can exchange genetic material—and therefore also resistance genes—with each other. One form of this horizontal gene transfer occurs in bacteria via so-called plasmids—mobile genetic elements. Scientists from the Institute of Medical Microbiology at Justus Liebig University Giessen (JLU), the German Center for Infection Research (DZIF) and public health institutions have now been able to identify a particularly stable plasmid that is responsible for the majority of bacterial resistance to antibiotics from various groups, including the carbapenems, in Germany. This high-risk plasmid cannot only be transferred to different bacterial species, it also remains active for years.

One of the most important and most common causes of bacterial carbapenem resistance worldwide is the enzyme KPC-2 carbapenemase, which renders carbapenems harmless. The research consortium was able to prove that regionally around 85 per cent of all pathogens that can produce a KPC-2 carbapenemase carry an almost identical plasmid that belongs to the group of IncN plasmids. This plasmid, which was described for the first time, encodes various antibiotic resistance genes and has a very broad bacterial host spectrum. It can be transferred quickly from one bacterium to another within a patient, including to other bacterial species. In the event of an outbreak—for example of the dreaded hospital infections—completely different bacterial pathogens are found, all of which carry the identical plasmid.

The study published in the journal Micobiology Spectrum focussed on carbapenem-resistant enterobacteria such as Escherichia coli or Klebsiella pneumoniae. The researchers analysed a total of more than 600 carbapenem-resistant Gram-negative bacterial isolates. They detected the IncN plasmid in eleven different bacterial species throughout Germany, in water samples from rivers and in a total of 77 patients in 28 hospitals in 20 cities.

"Our study shows that the possibility of exchanging resistance via mobile genetic elements is a key factor in the successful spread of multidrug-resistant Gram-negative pathogens," says PD Dr Can Imirzalioglu, co-author of the study and acting head of the Institute of Medical Microbiology at JLU. "The extent to which particularly successful plasmids exist and the extent to which these are decisive for the spread of pathogens in a supra-regional context had not yet been sufficiently investigated."

The IncN plasmids described by the research team were remarkably stable and maintained in individual patients carrying the bacterial pathogens for more than a year. "The resulting 'silent' transmission chains are a new challenge for the surveillance of multidrug-resistant pathogens, the investigation of outbreaks and the establishment of effective hygiene and infection prevention measures," says the first author of the study, Dr Yancheng Yao, a senior researcher in antibiotic resistance from the Institute of Medical Microbiology at JLU. "The identification of such high-risk plasmids and the development of new approaches to reduce their spread are highly topical tasks for research into antibiotic resistance."

"Genome-based surveillance of multidrug-resistant pathogens not only allows us to identify local outbreaks, but also to detect high-risk pathogens and resistances with supra-regional and international significance," adds Prof. Dr Trinad Chakraborty, former Director of the Institute of Medical Microbiology at JLU. "Conventional methods cannot detect such complex 'plasmid outbreaks', which are very difficult to recognise at first glance."

• Publication

Yancheng Yao, Linda Falgenhauer, Yalda Rezazadeh, Jane Falgenhauer, the IncN Study Group, Can Imirzalioglu, Trinad Chakraborty: Predominant transmission of KPC-2 carbapenemase in Germany by a unique IncN plasmid variant harbouring a novel non-transposable element (NTEKPC-Y). Micobiology Spectrum, published online on 12 December 2023
https://journals.asm.org/doi/full/10.1128/spectrum.02564-23

• Contact

PD Dr Can Imirzalioglu, MD
Institute for Medical Microbiology at Justus Liebig University Giessen
German Centre for Infection Research (DZIF), Gießen-Marburg-Langen site
E-Mail: can.imirzalioglu

Prof Dr Trinad Chakraborty
Institute for Medical Microbiology at Justus Liebig University Giessen
German Centre for Infection Research (DZIF), Giessen-Marburg-Langen site
E-mail: trinad.chakraborty

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