Antibiotic Resistance: Moving From Individual Health Norms to Social Norms in One Health and Global Health

Abstract

Antibiotic resistance is a problem for human health, and consequently, its study had been traditionally focused toward its impact for the success of treating human infections in individual patients (individual health). Nevertheless, antibiotic-resistant bacteria and antibiotic resistance genes are not confined only to the infected patients. It is now generally accepted that the problem goes beyond humans, hospitals, or long-term facility settings and that it should be considered simultaneously in human-connected animals, farms, food, water, and natural ecosystems. In this regard, the health of humans, animals, and local antibiotic-resistance-polluted environments should influence the health of the whole interconnected local ecosystem (One Health). In addition, antibiotic resistance is also a global problem; any resistant microorganism (and its antibiotic resistance genes) could be distributed worldwide. Consequently, antibiotic resistance is a pandemic that requires Global Health solutions. Social norms, imposing individual and group behavior that favor global human health and in accordance with the increasingly collective awareness of the lack of human alienation from nature, will positively influence these solutions. In this regard, the problem of antibiotic resistance should be understood within the framework of socioeconomic and ecological efforts to ensure the sustainability of human development and the associated human-natural ecosystem interactions.

Keywords: Global Health; One Health; antibiotic resistance; farming; waste water.

FIGURE 1

How the interactions among individual health, One Health, Global Health, and social norms influences antibiotic resistance. The right panel shows the different levels of dissemination of antibiotic resistance. In the left panel, the different types of norms (from individual to global norms) that can impact antibiotic resistance at each level are shown. These norms influence all levels of transmission: the individual promotes (red arrows) his own individual health, but doing it also promotes the health of the group, and the health of the group promotes Global Health of the human society at large. At each level, there is a positive action (red broken lines) on antibiotic resistance. Such dynamics largely depends on social norms (blue arrows) rewarding the individual or the groups whose behavior promotes health. Below the left panel, the basic social norm, progress and development, has consequences on the whole ecobiology of the planet (lower panel with bullet points), influencing the undesirable open circulation of antimicrobial resistant bacteria (with their mobile genetic elements) and antibiotic resistance genes.

FIGURE 2

Genetic, ecological, and socioeconomic elements mediating the transmission of antibiotic resistance. ARGs are ubiquitously present in any studied microbiome (A). However, only a few of them are transferred to human/animal pathogens, hence constituting a health problem. The genetics events implied include the acquisition of ARGs by gene-recruiting genetic elements such as integrons (B); the integration of these elements in MGEs as plasmids, bacteriophages, or insertion conjugative elements (C); and the acquisition of these elements by specific bacterial clones (D). These ARBs can share these elements among the members of gene-sharing communities (E) and also move among different ecosystems, including humans, animals (particularly relevant farm animals), and natural ecosystems (with a particular relevance for water bodies). The connection of these ecosystems, as well as the reduced diversity of animals, plants, and in general habitats as the consequence of human activities, allows the different microbiomes to be in contact, favoring ARGs transmission among the microorganism they encompass (F). This transmission is facilitated at the global scale by travel, animal migration, trade of goods, and eventually by meteorological phenomena, climate change included (G), hence producing a Global Health problem (H). While most studies on the dissemination of ARGs focus on MGEs (Davies, 1997; Muniesa et al., 2013; Lanza et al., 2015; Garcia-Aljaro et al., 2017), recent works suggest that the contribution of natural transformation (orange arrow), allowing the direct uptake of ARGs by natural competent microorganisms, may have been underestimated (Domingues et al., 2012; Blokesch, 2017). Further, competence can occur due to interbacterial predation (Veening and Blokesch, 2017), a biological interaction that may facilitate the acquisition of beneficial adaptive traits by predator bacterial species (Cooper et al., 2017; Veening and Blokesch, 2017). Other HGT mechanisms, such as DNA packing in extracellular vesicles (ECV) or transference of DNA through intercellular nanotubes, also seem to be relevant in nature (Dubey and Ben-Yehuda, 2011; Fulsundar et al., 2014). While the biotic conditions that may enhance HGT have been studied in detail, less is known concerning abiotic modulation of ARGs transfer. Under contemporary conditions, at least 10²⁴ microorganisms are affected by a freeze-and-thaw cycle, at least 10¹⁹ are agitated by sand, and at least 10¹⁷ are subjected to conditions suitable for electrotransformation every year (Kotnik and Weaver, 2016).

FIGURE 3

Local and global intervention strategies to tackle AR and knowledge gaps that could help improve existing ones. Most interventions for reducing antibiotic resistance are based on impairing the selection of ARBs/ARGs, which is just the first event in AR spread. Our main goal, as for any other infectious disease, would be reducing transmission. This does not mean that selective pressure is not relevant for transmission. Indeed, without positive selection, HGT events are not fixed, allowing the enrichment of some ARGs that are consequently more prone to diversification, both because they are more abundant and more frequently subjected to selection (Davies, 1997; Martinez, 2009a, b; Salverda et al., 2010) and because they can explore different landscapes when present as merodiploids in multicopy plasmids (Rodriguez-Beltran et al., 2018). Therefore, reducing the selective pressure, either due to antibiotics or by other coselecting agents as heavy metals, still stands as a major intervention against AR emergence and transmission. To address this issue, we need to know more on the amount of pollutants, their selective concentrations, and their mechanisms of coselection and cross-selection in different ecosystems. This is a general example illustrating the gaps in knowledge in the AR field that need to be filled as well as strategies that may help in tackling this problem. The figure includes several other examples of the gaps of knowledge (red) that require further studies and the interventions (blue) that may help to tackle AR.