Drug-resistant microorganisms with a higher fitness – can medicines boost pathogens?

Abstract

Drug-resistant microorganisms (DRMs) are generally thought to suffer from a fitness cost associated with their drug-resistant trait, inflicting them a disadvantage when the drug pressure reduces. However, Leishmania resistant to pentavalent antimonies shows traits of a higher fitness compared to its sensitive counterparts. This is likely due the combination of an intracellular pathogen and a drug that targets the parasite’s general defense mechanisms while at the same time stimulating the host’s immune system, resulting in a DRM that is better adapted to withstand the host’s immune response. This review aims to highlight how this fitter DRM has emerged and how it might affect the control of leishmaniasis. However, this unprecedented example of fitter antimony-resistant Leishmania donovani is also of significance for the control of other microorganisms, warranting more caution when applying or designing drugs that attack their general defense mechanisms or interact with the host’s immune system.

Keywords::

• Drug resistance
• fitness cost
• Leishmania donovani
• virulence
• visceral leishmaniasis

Acknowledgements

The authors thank Orkin.com for their consent to use the sand fly illustration used in Figure 3.

Declaration of interest

This work was financially supported by the European Commission’s Specific International Scientific Cooperation Activities [LeishNatDrug-R project, grant number ICA4-CT-2001–10076]; the European Commission’s Seventh Framework Programme [Kaladrug-R project, grant number 222895]; the Gemini consortia [grant number ITMA SOFI-B]; the Wellcome Trust [grant numbers WT 085775/Z/08/Z, 076355]; the Belgian Development Cooperation [grant number FA3 II Visceral Leishmaniasis Control]; the Baillet-Latour Foundation (fellowship to SD and MB) and the Agency for Innovation by Science and Technology in Flanders (fellowship to MV). The funders had no role in the design, data collection and analysis, decision to publish, or preparation of the manuscript.

The authors report no conflicts of interest.