Understanding copper- and silver-based antimicrobials and their potential in space applications

Maertens Laurens

Promoter

Matroule Jean-Yves, jean-yves.matroule@unamur.be

SCK•CEN Mentor

Van Houdt Rob
rob.van.houdt@sckcen.be
+32 14 33 27 28

SCK•CEN Co-mentor

Monsieurs Pieter
pieter.monsieurs@sckcen.be
+32 14 33 21 08

Expert group

Microbiology

PhD started

2017-10-01

Short project description

It is clear that crew health and safety need to be ensured during (long-term) space missions. To guarantee the health of the astronauts, several prevention, monitoring and mitigation measures are implemented by the space agencies to control microbial contamination (Novikova, 2004;Van Houdt and Leys, 2012;Van Houdt et al., 2012) and the development of improved spaceflight-suitable methods for microbiological monitoring, as well as contamination control and reduction is an important research area. One group of antimicrobials that are explored are metals, such as copper and silver, for which various studies indicated their potential (Boyce, 2016). However, bacterial resistance mechanism to these and other antimicrobials have been described repeatedly (Mijnendonckx et al., 2013a;Hobman and Crossman, 2015;Lawaree et al., 2016). Moreover, these resistance mechanisms are often strictly regulated, and currently, the main focus has been on the transcriptional network. Yet, recent research has shown the importance of post-transcriptional regulation via small regulatory RNAs (Vogel and Luisi, 2011;Papenfort and Vanderpool, 2015), a regulatory level which has been ignored so far when studying bacterial metal resistance. Nonetheless, it has been shown that the behavior of bacteria differs under space conditions with a central role for Hfq (Wilson et al., 2007), a RNA chaperone that interacts with those small regulatory RNAs. Therefore, the bacterial response to such metal-based antimicrobials needs to be thoroughly evaluated before possible implementation. Such tests are ideally performed on microorganisms isolated from space habitats, e.g. Cupriavidus metallidurans strains recently isolated from the ISS drinking water systems (Mijnendonckx et al., 2013b).

Objective

To main objective of this project is to study the response of bacteria to copper- and silver-based antimicrobials in the frame work of space applications. To dissect the problem, the focus will be on the metal ions, as many of the more complex compounds just ferry ions that are released and exert their action, and on Cupriavidus metallidurans strains isolated from actual contamination events that occurred in the ISS drinking water systems (Mijnendonckx et al., 2013b). Taking into account the role of Hfq during space flight (Wilson et al., 2007) and its altered gene expression after metal exposure (Monsieurs et al., 2011), a particular focus will be on post-transcriptional regulation via small regulatory RNAs, as this regulation level is barely studied in the context of copper and silver resistance. These data will support the assessment of metal-based antimicrobials for space applications and will scientifically underpin a recent ESA-approved science project on metal-based antimicrobials that is scheduled to be conducted onboard ISS (SCK•CEN is partner), but also their use in a more general context.

References
Boyce, J.M. (2016). Modern technologies for improving cleaning and disinfection of environmental surfaces in hospitals. Antimicrob Resist Infect Control 5, 10.
Hobman, J.L., and Crossman, L.C. (2015). Bacterial antimicrobial metal ion resistance. J Med Microbiol 64, 471-497.
Lawaree, E., Gillet, S., Louis, G., Tilquin, F., Le Blastier, S., Cambier, P., and Matroule, J.Y. (2016). Caulobacter crescentus intrinsic dimorphism provides a prompt bimodal response to copper stress. Nat Microbiol 1, 16098.
Mijnendonckx, K., Leys, N., Mahillon, J., Silver, S., and Van Houdt, R. (2013a). Antimicrobial silver: uses, toxicity and potential for resistance. Biometals 26, 609-621.
Mijnendonckx, K., Provoost, A., Ott, C.M., Venkateswaran, K., Mahillon, J., Leys, N., and Van Houdt, R. (2013b). Characterization of the survival ability of Cupriavidus metallidurans and Ralstonia pickettii from space-related environments. Microb Ecol 65, 347-360.
Monsieurs, P., Moors, H., Van Houdt, R., Janssen, P.J., Janssen, A., Coninx, I., Mergeay, M., and Leys, N. (2011). Heavy metal resistance in Cupriavidus metallidurans CH34 is governed by an intricate transcriptional network. Biometals 24, 1133-1151.
Novikova, N.D. (2004). Review of the knowledge of microbial contamination of the Russian manned spacecraft. Microb Ecol 47, 127-132.
Papenfort, K., and Vanderpool, C.K. (2015). Target activation by regulatory RNAs in bacteria. FEMS Microbiol Rev 39, 362-378.
Van Houdt, R., and Leys, N. (2012). "Monitoring the Microbial Burden in Manned Space Stations," in Stress Challenges and Immunity in Space, ed. A. Chouker. Springer Berlin Heidelberg), 299-308.
Van Houdt, R., Mijnendonckx, K., and Leys, N. (2012). Microbial contamination monitoring and control during human space missions. Planetary and Space Science 60, 115-120.
Vogel, J., and Luisi, B.F. (2011). Hfq and its constellation of RNA. Nat Rev Microbiol 9, 578-589.
Wilson, J.W., Ott, C.M., Honer zu Bentrup, K., Ramamurthy, R., Quick, L., Porwollik, S., Cheng, P., McClelland, M., et al. (2007). Space flight alters bacterial gene expression and virulence and reveals a role for global regulator Hfq. Proc Natl Acad Sci U S A 104, 16299-16304.