While antibiotics play a vital role in combatting harmful bacterial infections, overuse and misuse of antibiotics has led to the emergence of antibiotic resistance amongst particular microbial communities. Microbes become antibiotic resistant through various mechanisms that are derived from antibiotic resistant genes. In the presence of antibiotics, these bacteria out-live non-resistant bugs and multiply. The resistome represents the pool of antibiotic resistance genes present in a bacterial or fungal community, e.g. on the human skin.
How does antibiotic resistance occur?
Bacteria become antibiotic resistant through the introduction of resistance genes into their genomes or on plasmids, whether intrinsically by mutation or via acquisition.
Some of these resistance genes code for enzymes that degrade antibiotics; others are responsible for transporting antibiotics rapidly out of the cell again. The result is that pathogenic microorganisms are able to survive antimicrobial therapy (Walsh, 2003).
Bacteria can have one or multiple resistance genes – or, indeed, none. However, non-resistant bacteria can acquire resistance by obtaining resistance genes from other bacteria through gene transfer. This can spread through a microbial population where selective pressure occurs, meaning resistance genes can remain in a population– even if the original carrier bacterium is no longer present.
It is also possible for resistance genes to be transmitted between different microbial habitats, e.g. from the skin to the intestinal microbiome.
Selective pressure is an important factor for specific genes to remain in a population; in the case of antimicrobial resistance genes, the particular pressure is the presences of antibiotics or other antimicrobial agents (e.g. disinfectants or preservatives). The lower this pressure is, the lower the number of resistance genes remaining will be and over time a “washout” effect may be observed. Overuse and misuse of antibiotics is increasing this pressure – hence creating a cause for concern.
Research around the resistome can be used to investigate the evolution of resistance genes from the past to the present (Perry et al., 2014).
How do we identify the resistome?
The resistome can be determined using amplicon, metagenome or transcriptome sequencing. Either a set of primers targeting known antibiotic resistance coding genes is used for amplification and sequencing or the whole DNA or RNA present in a sample is amplified and sequenced. Analysing the human gut resistome is an example of the techniques used (van Schaik, 2015).
The resistome of the skin
Commensal bacteria in the microbiome are not immune to developing resistance. Indeed, among the bacteria found in the skin microbiome, Staphylococcus aureus and Staphylococcus epidermidis, in particular, are known to be carriers and “transmitters” of resistance genes. This is also the case for Cutibacterium acnes, although at a much lower extent.
Among the most feared bacteria are MRSA (multiple resistant or methicillin resistant S. aureus) that can cause severe infections. People with MRSA infection may be ill but MRSA are also present on the skin and in the nasal mucosa of healthy persons. In either case, MRSA can be transmitted to other persons, leading to failure of antibiotic treatments and, thus is a threat to public health (Sakr et al., 2018).
Microorganisms present on the skin – antibiotic resistant or not – can also be transmitted to other consortia of the body, e.g. to the intestine of infants by breastfeeding (Hourigan et al., 2018; Pärnänen et al., 2018), from the nasal mucosa to the face and vice versa. Bacteria can also be transferred to the skin from other persons, animals and the environment, either by direct or indirect contact. If resistant bacteria are transmitted, they may be able to integrate themselves in the skin microflora or, instead, may transmit their resistance genes to “normal” skin bacteria.
Beyond these routes of resistance emergence and transfer, the use of cosmetics can influence the development and maintenance of resistant bacteria on the skin. Some additives used in cosmetics trigger the same resistance mechanisms as antibiotics and, thus, provide selective pressure to select and maintain resistant bacteria within the skin’s microbial population (Russell, 2003).
A 2018 study analysed the microbiomes and resistomes of passengers of the Hong Kong metro, both before and after using the metro (Kang et al., 2018). Depending on metro line and time, variations in the presence of resistance genes were observed. Clinically relevant tetracycline and vancomycin resistance genes were detected on the hands of some passengers. It was not further investigated, however, whether these resistance genes became “established” afterward on the hands of the passengers or were temporary.
Changing the skin resistome
Could it be possible to change the resistome? For example, could we eradicate unwanted resistance genes from the skin microbiome?
In theory, the following approach could be a way to achieve this:
First, the host organisms that carry the “unwanted” genes would have to be removed, e.g. by using skin care products that target these hosts and kill them. Then, the ecological niche now present on the skin would have to be “filled” with commensal organisms. These organisms could already be present on the skin and their growth stimulated or probiotics could be used.
Any eradication strategy would have to take into consideration that resistance genes can circulate and survive within a population and that removing only one potential host bacterium may not be enough to eliminate the gene from the habitat.
Methods that aim to selectively change the resistome by targeting resistant bacteria instead of trying to modify the general composition of the microbiome could support the ongoing strategy of the WHO to fight antibiotic resistance.
Want to read more around the skin microbiome? Explore the Microbiome Basics here or hear from our other experts in the Views from section of the Content Hub.
References
1. Hourigan, S.K., Subramanian, P., Hasan, N.A., Ta, A., Klein, E., Chettout, N., Huddleston, K., Deopujari, V., Levy, S., Baveja, R., Clemency, N.C., Baker, R.L., Niederhuber, J.E., Colwell, R.R., 2018. Comparison of Infant gut and skin microbiota, resistome and virulome between neonatal intensive care unit (NICU) environments. Front. Microbiol. 9, 1361. https://doi.org/10.3389/fmicb.2018.01361
2. Kang, K., Ni, Y., Li, J., Imamovic, L., Sarkar, C., Kobler, M.D., Heshiki, Y., Zheng, T., Kumari, S., Wong, J.C.Y., Archna, A., Wong, C.W.M., Dingle, C., Denizen, S., Baker, D.M., Sommer, M.O.A., Webster, C.J., Panagiotou, G., 2018. The environmental exposures and inner- and intercity traffic flows of the metro system may contribute to the skin microbiome and resistome. Cell Rep. 24, 1190-1202.e5. https://doi.org/10.1016/j.celrep.2018.06.109
3. Pärnänen, K., Karkman, A., Hultman, J., Lyra, C., Bengtsson-Palme, J., Larsson, D.G.J., Rautava, S., Isolauri, E., Salminen, S., Kumar, H., Satokari, R., Virta, M., 2018. Maternal gut and breast milk microbiota affect infant gut antibiotic resistome and mobile genetic elements. Nat. Commun. 9, 3891. https://doi.org/10.1038/s41467-018-06393-w
4. Perry, J.A., Westman, E.L., Wright, G.D., 2014. The antibiotic resistome: what’s new? Curr. Opin. Microbiol. 21, 45–50. https://doi.org/10.1016/j.mib.2014.09.002
5. Russell, A., 2003. Biocide use and antibiotic resistance: the relevance of laboratory findings to clinical and environmental situations. Lancet Infect. Dis. 3, 794–803. https://doi.org/10.1016/S1473-3099(03)00833-8
6. Sakr, A., Brégeon, F., Mège, J.-L., Rolain, J.-M., Blin, O., 2018. Staphylococcus aureus Nasal Colonization: An update on mechanisms, epidemiology, risk factors, and subsequent infections. Front. Microbiol. 9. https://doi.org/10.3389/fmicb.2018.02419
7. van Schaik, W., 2015. The human gut resistome. Philos. Trans. R. Soc. B Biol. Sci. 370, 20140087. https://doi.org/10.1098/rstb.2014.0087
8. Walsh, C., 2003. Antibiotics: Actions, Origins, Resistance. American Society of Microbiology. https://doi.org/10.1128/9781555817886