University of Gothenburg

The BIOCIDE research project - Background & Science

The overall aim of BIOCIDE is to determine how antibacterial biocides contribute to the development and spread of antibiotic resistant bacteria in different aquatic/marine ecosystems, and to inform and enable measures that ultimately protects human health and safe water resources for both humans and wildlife.

BACKGROUND - a short introduction


The emergence and global dissemination of antibiotic (AB) resistant bacteria has developed into a severe threat to public health, jeopardizing our ability to treat bacterial infections, cure cancer and perform advanced surgery, all of which are dependent on effective ABs.

Our extensive use of ABs and insufficient measures to prevent the spread of resistant bacteria are primary drivers of resistance. However, the external environment also contributes i) as a transmission route for several bacterial pathogens and ii) in the evolution and emergence of resistance in pathogens, as the immense diversity of environmental bacteria serves as a source for resistance genes through horizontal gene transfer.

A “one health perspective”, considering the ability of bacteria and genes to move between humans, animals and the external environment, is therefore needed to understand and efficiently manage resistance development.

In addition, co-selection from antibacterial biocides (i.e., chemicals with antibacterial properties that are not used for treating infections) can drive resistance development. These include metals and numerous organic biocides used, for example, as disinfectants in health care, as antifoulants, as preservatives, or as antibacterial agents on clothes and in household products. In addition to their specific sites of applications, biocides are widely disseminated in the environment, particularly via wastewater streams, into waterways and eventually oceans. While well justified in certain settings (e.g. disinfection in hospitals), our extensive use is likely to promote AB resistance.

There are at least two main mechanisms by which biocides may co-select for AB resistance. The first involves co-resistance, where the biocide resistance genes are present on the same, mobile genetic element (e.g., a plasmid) as the AB resistance genes. Such co-localization will indirectly select for AB resistance. The second is, referred to as cross-resistance where the biocide and the AB share a common resistance mechanism (e.g., up-regulation of efflux pumps). For both these mechanisms, exposure to biocides will directly and inevitably enrich already co-resistant strains, and thus promote their dissemination and ultimately increase transmission risks.

In addition, there is evidence that the immense genetic diversity of the environmental microbiome contributes to emergence of novel mobile AB resistance determinants in pathogens; these are less common evolutionary events but with potentially profound consequences. Here, selection from biocides could very well play a key role if cross-resistance is involved, while this is not the case for co-resistance – unless the different genes are linked from the very beginning. Therefore, understanding the relative roles of co- versus cross-resistance mechanisms in co-selection is essential to assess and manage different risk scenarios.

Moreover, the mechanism of resistance and the involved genes remain unknown for most biocides, preventing us from evaluating the link to AB resistance.

Not only do biocides have the potential to select for resistance, but also to increase horizontal gene transfer (HGT), two processes that together can exacerbate the resistance problem. Typically, effects on HGT through conjugation have only been studied using model strains, limiting generalizations. Several biocides can generate intracellular reactive oxygen species (ROS) which, in turn, provoke an SOS response leading to plasmid transfer initiation. To what extent this mechanism is conserved across bacteria is unknown.


Outcomes and expected impact

We will provide means to guide action both at the source (approval), and in other parts of the water cycle. Standardization of methodology will facilitate possible future inclusion in regulatory systems in Europe and elsewhere. Here, the involvement of stakeholders, particularly regulatory bodies, in the process is important. The maritime sector will receive guidance to improve sustainable transports by a better understanding of potential human health risks associated with antifouling agents (also used in e.g. fish farming). While our ultimate goal is to protect the ability to prevent and treat bacterial infections using antibiotics, the generation of analytical tools, environmental exposure data and effect data for a range of microorganisms will also inform risks for ecological effects.


Generated data will include

1) exposure levels in different matrices,

2) concentrations that are likely to co-select for antibiotic resistance and promote horizontal gene transfer,

3) identification of predominant and novel genetic mechanisms for co-selection, as well as

4) a risk assessment.