Dr. Karsten Filzmaier

Antibiotic resistance can also occur in rare diseases

These days, resistance to antibiotics is a worldwide problem in the treatment of bacterial infections. For some time, the classic antibiotics such as penicillin have no longer helped against many bacteria. And humans are responsible for most of this resistance, by their uncritical use of antibiotics both in medicine and in intensive animal husbandry. But certain pathogens can apparently also develop resistance naturally. Does this mean that there is a danger of new epidemics of disease that were virtually eradicated a long time ago?

Resistance to antibiotics is an enormous health and economic problem. To mention just a few, antibiotic-resistant bacteria are common in tuberculosis, gonorrhoea and lung infections, as well as in many nosocomial bacteria such as enterococci and staphylococci. The consequences are prolonged hospital stays, higher mortality and increased costs because of the necessary isolation measures. Furthermore, reserve antibiotics that are generally more expensive have to be used; in many cases, these lead to a wider range of side effects. Much antibiotic resistance is the result of using inappropriate antibiotics or excessive amounts to treat people. But the use of antibiotics in intensive animal husbandry seems to have had incalculable effects on the spread of antibiotic resistant micro-organism.

All the more amazing, then, when a plague strain discovered in Madagascar in 1995 was found to be resistant to no fewer than eight different antibiotics, including all those used to treat plague. The pathogen responsible for plague, a bacterium called Yersinia pestis, had not previously been under any selection pressure because of inappropriate or excessive treatment with antibiotics. Similarly, no resistance of Y. pestis had been reported before that time and the mortality of infections with the plague had been reduced to 10% with the antibiotic agents then in use. Even though the plague is still active in many parts of the world, just 18,739 cases registered by WHO between 1980 and 1994 mean that this is a relatively rare infectious disease, although the number of newly notified cases has increased slightly in recent years.

Research workers investigated the new resistant plague strain and discovered a plasmid in these bacteria, which was responsible for the resistance. This was designated pIPI202. Plasmids are ring-formed DNA structures which contain genetic information – in this case, for antibiotic resistance. Plasmids can be exchanged between bacteria in a process known as conjugation, which is one way of replacing the sexual mixing of genes that occurs in higher life forms.

The researchers were not able to explain where the plasmid came from, but the fact that Y. pestis could gain a plasmid for antibiotic resistance transmitted by natural means revealed a previously unknown mechanism, and this was considered to be thoroughly alarming. This concern was augmented by the fact that the plasmid could also be transmitted to non-resistant Y. pestis strains under laboratory conditions and thus further disseminated.

But where did Y. pestis get this plasmid from? So far, an unanswered question. But American scientists have now discovered a plasmid, almost identical to the pIPI202 plasmid from Madagascar, in multiresistant Salmonella from ordinary meat specimens. This observation suggests that the resistant Y. pestis strain got its plasmid either from the resistant Salmonella or from yet another bacterium acting as a "go-between" or even as the main transmitter. The ecological niche in which this transmission took place is still not clear. However, researchers in 2002 were able to perform a plasmid transfer from an intestinal bacterium to Y. pestis in the midgut of fleas. Fleas are the natural reservoir of plague organisms and can transmit the disease to humans through their bite. And the chances of the resistant Salmonella and Y. pestis coming into close contact somewhere in nature, possibly even in the gut of a flea, do not seem remote.

What conclusions can we draw from these observations?

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  Antibiotic resistance can be transmitted to non-resistant plague bacteria naturally in the wild and without selection pressure.
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  Acquired resistance can also potentially be passed on between strains of Y. pestis.
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  This process does not have to be specific for Y. pestis but may possibly also occur in other species of bacteria.

What further questions do these observations raise?

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  Is this phenomenon a rare, isolated, one-off case or a normal, natural evolutionary process that is considerably more common than previously suspected?
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  Where did the plasmid transfer take place and via which bacterium?
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  Can resistant strains of Y. pestis be disseminated by host animals?

The likelihood that Y. pestis will become a multiresistant bacterium through plasmid transfer is relatively small. In addition, there is a whole range of other antibiotics that are effective against the new plague strain. And these were used to save the life of the 16-year-old boy in Madagascar from whom the resistant bacterium was isolated.