Science of the Total Environment 717 (2020) 135001 Contents lists available at ScienceDirect Science of the Total Environment journal homepage: www.elsevier.com/locate/scitotenv Review Wild boar as a reservoir of antimicrobial resistance Rita Tinoco Torres a,1,⇑, Joana Fernandes a,1, João Carvalho a, Mónica V. Cunha b,c,d, Tânia Caetano a, Sónia Mendo a, Emmanuel Serrano e,f, Carlos Fonseca a a Department of Biology & CESAM, University of Aveiro, Portugal b National Institute for Agrarian and Veterinary Research (INIAV, IP), Av. da República, Quinta do Marquês, 2780-157 Oeiras, Portugal c Centre for Ecology, Evolution and Environmental Changes (cE3c), Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisbon, Portugal d Biosystems & Integrative Sciences Institute (BioISI), Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisbon, Portugal e Wildlife Ecology & Health group (WE&H), and Servei d’Ecopatologia de Fauna Salvatge (SEFaS), Departament de Medicina i Cirurgia Animals, Facultat de Veterinària, Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain f Dipartimento di Scienze Veterinarie, Universitá di Torino, Grugliasco, Torino, Italy h i g h l i g h t s g r a p h i c a l a b s t r a c t  Literature related to antimicrobial resistance of wild boar in Europe is reviewed.  Growing interest in antimicrobial resistance in wild boar is highlighted.  Wild boar are carriers of antimicrobial resistant bacteria.  Research trends and future directions are discussed. a r t i c l e i n f o a b s t r a c t Article history: Antimicrobial resistance (AMR) has been recognized as an emerging and growing problem worldwide. Received 1 August 2019 Knowledge concerning AMR bacteria circulating in wildlife is currently limited, although it could provide Received in revised form 19 September important insights into AMR emergence and persistence. Across Europe, wild boar (Sus scrofa) popula- 2019 tions have dramatically increased their distribution and number over the last decades. In the context Accepted 14 October 2019 Available online 23 November 2019 of AMR dynamics, wild boar is a perfect model species to unveil the emergence, spread and persistence of AMR at the human-livestock-wildlife interface. Here, we summarize the current knowledge on the Editor: Dr. Damia Barcelo importance of wild boar as a reservoir of antimicrobial resistant bacteria, and its possible use as sentinel species for surveillance. Analyses of available data showed a rising interest on this topic in the last years, Keywords: highlighting the growing concern on wild boar potential role as AMR facilitator and it is foreseen that the Wild boar importance of antimicrobial resistance research in wild boar will continue to increase in years to come. Antimicrobial resistance Available studies have been focused on specific bacterial species, particularly E. coli, Salmonella spp. Ungulates and Enterococcus spp., bioindicators of AMR, and have been mainly conducted in three countries: Spain, Wildlife Portugal and Germany. Strikingly, AMR surveillance in wild boar is uneven and still poorly allocated as One health many wild boar high-density countries do not yet have publications on the topic. Overall, accumulated data showed that wild boar are carriers of antimicrobial resistant bacteria, with variation in the preva- lence of bacterial species and the percentage of resistance to different antibiotics. The lack of harmonized sampling and testing protocols makes it difficult to compare AMR in wild boar. The need for the estab- lishment of standardised protocols keen to provide quantitative comparable data is highlighted. We ⇑ Corresponding author at: CESAM & Department of Biology, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal. E-mail address: rita.torres@ua.pt (R.T. Torres). 1 both authors contributed equally to this work. https://doi.org/10.1016/j.scitotenv.2019.135001 0048-9697/Ó 2019 Elsevier B.V. All rights reserved. 2 R.T. Torres et al. / Science of the Total Environment 717 (2020) 135001 finally suggest the long-term monitoring of wild boar as a sentinel species for AMR surveillance in order to inform public policies on this topic. Ó 2019 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 2. Methodological approach. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 3. Results and discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 3.1. Temporal evolution of publications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 3.2. Distribution of bacterial species in the published studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 3.3. Publication by country . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 3.4. Diversity of antimicrobial resistance patterns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 4. Conclusions and future perspectives. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Conflict of interest statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Appendix A. Supplementary data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 1. Introduction underestimating the tremendous importance of the animal com- partment in contributing on AMR dissemination. The ‘One Health’ Antimicrobials have revolutionised human healthcare practices concept involves a focus on the multiple interfaces of AMR surveil- worldwide (Spellberg et al., 2013). They have saved millions of lance: human, animal (livestock and wildlife) and environmental. lives. For example, penincillin lowered mortality associated with Given the complexity of the antimicrobial resistance challenge, it pneumococcal pneumonia from 20–40% to 5% (Laxminarayan seems particularly important to emphasize the role of a One Health et al., 2016). Nevertheless, shortly after the discovery of the ‘‘magic approach in addressing the problem, since it considers the under- pill”, antimicrobial resistance (AMR) became a serious problem lying factors that influence AMR, including the socio-political, threatening the advances of the prior decades (Ventola, 2015). This environmental, biological and economic factors (Kock, 2015; resulted in a general reduction of the efficacy of antibiotics, leading Lammie & Hughes, 2016). This is particularly true in the current the World Health Organizaton to identify AMR as a global, emerg- scenario of antropogenic transformation of the landscapes, where ing, and unparalleled problem for public, animal and environment natural habitats become increasingly fragmented, forcing wildlife health (WHO, 2014). Although the development of natural resis- into greater contact, both direct and indirectly, with humans and tance by some bacteria is an old and natural phenomenon their livestock, ultimately increasing the opportunities for antimi- (D’Costa et al., 2011), the acquired resistance is mostly due to the crobial resistance transmission among populations (Jones et al., underuse, overuse, and misuse of antibiotics (Davies, 1996; 2008). This inextricable connection between human populations, Lammie & Hughes, 2016). In fact, antibiotic consumption is consid- animals and the ecosystems further complicates the picture, ered the primary driver of antibiotic resistance (Klein et al., 2018). strengthening the requirement for an integrated approach for AMR is an urgent global problem, recently compared to the human, animal and environmental health (Zinsstag et al., 2011). challenges of climate change since it is a global scale natural pro- Although AMR has already been reported in commensal bacte- cess that has been aggravated by human activity (Woolhouse ria of wildlife, which have the potential to act as reservoirs and dis- et al., 2015). The loss of efficacy of antibiotics to common patho- persers of resistance genes (Arnold et al., 2016; Vittecoq et al., gens creates a huge clinical problem. Over 700,000 deaths world- 2016), the knowledge concerning AMR bacteria circulating in wild- wide are attributable to resistant bacterial pathogens each year life is still limited. It is generally accepted that wildlife populations (Laxminarayan et al., 2016). AMR is a complex, multi-layered prob- living in close proximity to humans exhibit higher levels of resis- lem, that does not recognize national borders, requiring an holistic tance: 95% of the bacterial isolates from rodents captured in rural framework to address it (Queenan et al., 2016; Walsh, 2018). England were resistant to antibiotics (Gilliver et al., 1999) while The AMR problem is not however confined to the human com- natural populations of moose, deer and voles in Finland had almost partment, since part of the resistance burden in humans is attribu- no resistance (Österblad et al., 2001). It is therefore hipothethised table to antimicrobial use in livestock production, primarily for that contact with humanized environments can enhance wildlife disease prevention and growth promotion (Marshall & Levy, contact with resistant bacteria as well as with selective agents 2011). For example, antimicrobials used in livestock are expected and commensals from humans and other species, while vice- to account for circa 80% of the U.S.A. (Spellberg et al., 2016) and versa is also applicable (Vittecoq et al., 2016). Consequently, wild- 84% of China’s annual antimicrobials consumption (Zhang et al., life populations living in close contact to humans or agricultural 2015). Impressive doses of antimicrobials are also used in agricul- areas have shown to exhibit higher levels of resistance (Gilliver ture, aquaculture and horticulture, to prevent infection, making et al., 1999; Allen et al., 2011; Bondo et al., 2016; Furness et al., resistance widespread in those settings as well (Hoyle et al., 2017). Resistance however is not ubiquitous among wildlife spe- 2006; Laxminarayan et al., 2013). Several authors have advocated cies and different life-history traits may predispose some species that the rising threat of AMR requires a holistic and multidisci- as key actors in the cycle of AMR transmission. Wildlife species plinary approach – a One Health perspective (Collignon et al., with a close association or tolerance for humans have been associ- 2018; Puyvelde et al., 2018; Walsh, 2018) and that we have been ated with the increase in AMR, with species foraging near human R.T. Torres et al. / Science of the Total Environment 717 (2020) 135001 3 settlements and farms reported as harbouring significant amounts search strategy consisted of compiling search strings, one for each of AMR bacteria (Rolland et al., 1985; Pesapane et al., 2013). It is category (antimicrobial resistance and wild boar) and combining obvious that wildlife can act as a potential, but still understudied, these by the Boolean operator ‘‘AND” to obtain only the intersec- reservoir and disperser for AMR in the human-livestock-wildlife tion. Specifically, we used the following Boolean search statement: interface (Dhama et al., 2013), representing a major epidemiologi- ‘antimicrobial’ OR ‘antibiotic’ AND ‘resistant’ OR ‘resistance’ AND cal link between natural and humanized environments, represent- ‘wild boar’ OR ‘Sus scrofa’. No time restrictions were placed on ing an additional challenge for human health, and hindering the these searches, but locations were restricted to Europe, and only management of wildlife species (Arnold et al., 2016; Vittecoq those published in English retrieved. The searches were last et al., 2016). updated on 24th April 2019. Results for all articles were imported Wild boar (Sus scrofa) is considered one of the most extensively into a bibliographic referencing tool and assessed for relevance, distributed mammals of the world, colonizing and occupying a removing articles that did not contain information relating to variety of environments, from natural habitats to urban areas, AMR in wild boar. All query results were verified manually before exhibiting high tolerance to human disturbance, while also explor- excluding duplicates. In addition, publications clearly indexed ing anthropogenic food available in these environments. In the last either as review, editorial, or errata were excluded. Bibliometrics, decades, wild boar have experienced dramatically increases in which is increasingly used to quantitatively assess scientific data number and distribution all over Europe and are now one of the and their trends over time, was used to evaluate and quantify most numerous and hunted ungulate species in Europe (Massei the number and growth trend of the publications (Aria & et al., 2015; Pittiglio et al., 2018). As a consequence of this expan- Cuccurullo, 2017). The bibliometric analysis was performed on sion, new management challenges arise: its wide distribution and the full search results using the bibliometrix package in R (Aria & link between natural and humanized environments places this Cuccurullo, 2017). species in a central place as reservoir or carrier of several zoonotic pathogens, such as the agents of tuberculosis and brucellosis, or 3. Results and discussion pathogens that can spill-over to domestic swine causing tremen- dous economic losses and embargo to animal trade, such as African 3.1. Temporal evolution of publications swine fever virus (Fredriksson-Ahomaa, 2019). In the context of AMR dynamics, wild boar are perfect model species to unveil the Overall, a total of 88 documents were found in the ISI’s Web of emergence, spread and persistence of AMR in the wildlife- Science. From these, we selected those presenting novel data about livestock interface. They are ubiquitous, have considerably large antimicrobial resistance in free-ranging wild boar but excluded home ranges, are unlikely of being treated with antibiotics, at least those living in captivity. In addition, publications clearly indexed in the wild setting, and overlap their habitat and distribution with either as review, editorial, or errata were excluded. In the end, only livestock and humans, serving as a link between human-influenced 40 peer-reviewed articles were included in the review. The full list settings and natural areas (Macdonald & Laurenson, 2006). Addi- of articles is presented in Appendix S1. Publications focusing on tionally, wild boar hunting and the manipulation of wild boar meat AMR in wild boar in Europe are relatively recent and date from in various countries of the world are direct routes of transmission 2007 to 2019 (Fig. 1). The number of documents on this topic of resistant bacteria and associated genes between this species and has grown since 2007 until now, with some exceptions, particu- humans. As the number of hunters across Europe appears to be larly in years 2008, 2015 and 2016 (Fig. 1). The maximum number either stabilizing or decreasing (Riley et al., 2003; Massei et al., of documents on antimicrobial resistance in wild boar was pub- 2015) and considering that hunting is the main source of wild boar lished in the last two years of the period, in 2017 and 2018, with population control, with urban wild boars nowadays a reality in a total of 12 publications. It is important to stress that 2019 should several European countries (Castillo-Contreras et al., 2018), follow the same trend as the database was last updated in April chances are that contact between wild boar and livestock and 2019. Overall, the temporal trend in publication on antimicrobial human will dramatically increase. These facts highlight the poten- resistance in wild boar shows a growth in the number of docu- tial of wild boar as an important reservoir, and disperser of bacteria ments published per year, with an annual percentage growth rate with antimicrobial resistance, posing additional concerns to public of 3,44% (Fig. 1). This trend evidences a growing awareness of the health. scientific community on the importance of wildlife, and in partic- However, despite its potential role in the AMR dynamics, which ular of wild boar, in the dynamic of antimicrobial resistance. Given is of paramount importance to human health because of the this tendency, it is envisaged that the number of documents pub- increasing importance of zoonotic diseases, no attempt has been lished on this topic will continue to rise in the upcoming years. made to provide a comprehensive analysis of the knowledge accu- mulated to date regarding antimicrobial resistance in this species. Here, we systematically summarize the current understanding on 3.2. Distribution of bacterial species in the published studies the importance of wild boar as a reservoir of antibiotic resistant bacteria, and its possible use as sentinel species for surveillance, The vast majority of studies focusing on AMR in wild boar did in Europe, where wild boar populations have greatly increased in not investigate antimicrobial susceptibility of the whole commen- the last decades, while discussing present knowledge gaps and sal bacteria community, but focus on specific isolated bacterial future challenges. species (Fig. 2), particularly in Escherichia coli, Salmonella spp. and Enterococcus spp., as bioindicators for faecal contamination and AMR. Generally, the search is driven by human health and vet- 2. Methodological approach erinary concerns associated with the focus bacteria (Vittecoq et al., 2016). E. coli is part of the normal gut microbiota of mammals in To gather the peer-reviewed database, literature searches were general, and humans in particular, and can easily be disseminated undertaken using major search engines and the resulting articles in different ecosystems, being used as an indicator species. Sal- were manually reviewed. The literature search was conducted monella spp. is among the main causes of foodborne outbreaks through the ISI’s Web of Science online interface (http://www.isi- and one of the most reported agents of zoonotic diseases in knowledge.com). Search results were delimited based on the fol- humans in Europe, with numbers of confirmed cases reaching over lowing Boolean query executed within a single search. The 90,000 in 2017 (EFSA and ECDC, 2018). This microorganism is con- 4 R.T. Torres et al. / Science of the Total Environment 717 (2020) 135001 Fig. 1. Trends in number of publications on antimicrobial resistance in wild boar from 2007 to 2019. Fig. 2. Number of publications focusing on specific bacteria. sidered a multi-host pathogen with a long environmental persis- prevalence (about 3%) in northeast Spain. Similarly, Salmonella spp. tence (Murray, 1991), being able to be transmitted among humans occurred in populations of wild boar at different prevalence rates. and other animal species, with reports of outbreaks tracked down In Germany, Salmonella spp. was isolated from 67% of wild boars to wildlife (Methner et al., 2018). Enterococci are part of the nor- (Methner et al., 2018) and, in Italy, the prevalence was similar, mal microbiota of healthy animals and humans but they can also with about 66% of wild boars being Salmonella spp. carriers act as pathogens that are able to cause different diseases of vari- (Zottola et al., 2013). Both these report the highest prevalence of able severity (Lozano et al., 2016). Furthermore, they have emerged Salmonella spp.. In central Portugal, Dias et al. (2015) recorded a as important causes of nosocomial and community acquired infec- prevalence of 5% while Navarro-Gonzalez et al. (2013) reported tions due to their ability to acquire virulence traits and increasing similar prevalence in Barcelona (Spain). In northeast Spain, the vancomycin resistance (Poeta et al., 2007a, 2008; Guerrero-Ramos prevalence of Salmonella spp. in cattle and cattle-free areas was et al., 2016). compared and, interestingly, the occurrence of Salmonella spp. in Across Europe, studies reported a high variability in the preva- wild boars from cattle areas was two times higher (35.67%) than lence of the three bacterial groups mentioned. Escherichia coli has in cattle-free areas (17.54%) (Navarro-Gonzalez et al., 2012). When been reported in wild boar populations with variable prevalence: we consider Enterococcus spp. in Portugal, reported prevalence can higher prevalence was reported for several countries, with E. coli be up to 50% (Poeta et al., 2007a) with similar values reported in being found in 99% of wild boars in Czech Republic (Literak et al., Spain (Navarro-Gonzalez et al., 2018), while lower prevalence rates 2010) and in up to 96% in central Portugal (Dias et al., 2015). It (25.9%) were reported in Slovenia (Križman et al., 2017). Fewer was also reported with a similar prevalence for Serbia (Velhner studies focused on Staphylococcus aureus in wild boar populations et al., 2018), while Navarro-Gonzalez et al. (2015) reported a lower and its lowest prevalence rate was reported for Germany at 4.8% R.T. Torres et al. / Science of the Total Environment 717 (2020) 135001 5 Table 1 continue to grow, as well as urban wild boar populations, therefore Publication distribution by country. more work is needed to implement, and supplement, surveillance Country N° publications % gaps. Spain 12 33 Portugal 9 23 Germany 2 18 3.4. Diversity of antimicrobial resistance patterns Austria 2 5 Italy 2 5 When comparing studies across Europe, it is clear that the Poland 2 5 prevalence rates of bacterial species in wild boar are highly vari- Switzerland 1 3 able and so are their antimicrobial susceptibility profiles and resis- Czech Republic 1 3 Slovenia 1 3 tance genes. Available studies tested the recovered bacteria against Serbia 1 3 several antimicrobial agents and the percentage of resistance asso- ciated was demonstrated to be variable according to both geo- graphical location and the examined strains. In addition, the (Kraushaar & Fetsch, 2014), while its highest was reported in the susceptibility testing methods used also vary, making comparisons same country with 36.9% of wild boar samples testing positive of antimicrobial susceptibility phenotypes of bacteria from wild for this pathogen (Seinige et al., 2017). boar sampled in different geographic origins difficult. Recently, studies have been interpreting bacterial susceptibility profiles based on their epidemiological cut-off values (ECOFFs) (e.g. Sousa 3.3. Publication by country et al., 2017; Methner et al., 2018; Navarro-Gonzalez et al., 2018; Dias et al., 2019), allowing to distinguish between wild type Research has not been focused evenly on all European countries (WT) bacteria from bacteria with acquired resistance mechanisms but is under particular focus in three of them: Spain (accounts for (non-wild type – NWT), facilitating comparisons. 33% of the publications), Portugal (23%) and Germany (18%) For E. coli, the prevalence of overall antimicrobial resistance (Table 1). Altogether, these three countries have published 74% of varied between 0.9% in Italy (Bonardi et al., 2019) and 25% in Por- the total number of papers dealing with antimicrobial resistance tugal (Dias et al., 2015). Regarding Salmonella spp., the prevalence in wild boar. The low contribution of Switzerland, Czech Republic, of resistance was generally higher with all isolates being resistant Slovenia and Serbia is notable, with only one publication per coun- to at least one antimicrobial in Germany (Methner et al., 2018) and try. Sample type and collection was also highly variable across up to 93% in Spain (Gil Molino et al., 2019). On the other hand, studies with faecal samples representing nearly half the studies lower prevalence rates were reported for Spain (3%) (Navarro- included (Appendix S1). Gonzalez et al., 2012). For the indicator bacteria Enterococcus Wild boar distribution is generalized across Europe, with densi- spp., the prevalence of antimicrobial resistance varied between ties varying from 0.01 to 43 animals/km2 (Pittiglio et al., 2018). 4.9% (Lozano et al., 2016) and 95%, both rates reported for the same Fig. 3 shows that the effort for AMR surveillance in wild boar is still country, Spain (Navarro-Gonzalez et al., 2013). The highest per- poorly allocated, as there is a mismatch between areas or counties centages of resistance have been recorded for sulphonamides, with some AMR monitoring and countries where densities are the tetracyclines and penicillins (Dias et al., 2015; Gil Molino et al., highest. This highlights the critical need for wild boar monitoring 2019; Leekitcharoenphon et al., 2019). This is not a surprising in these high-density areas. Wild boar densities are expected to trend, since these antimicrobials were indicated as having the Fig. 3. Distribution of the publications by country and by bacterial genus with wild boar density illustrated. Each point corresponds to the study areas and can include more than one study and one bacteria (wild boar density map adapted, with permission, from Pittiglio et al. 2018 Ó Plos One). 6 R.T. Torres et al. / Science of the Total Environment 717 (2020) 135001 highest sale rates for livestock in the last report of the European instead a wider environmental issue of public health concern. Surveillance of Veterinary Antimicrobial Consumption (ESVAC, Although previous studies have demonstrated the presence of 2018), accounting for 70% of the total sales in 2016. Sales of AMR and resistance genes in wildlife (for review Arnold et al. polymyxins also increased in 2016 by 69%, compared to 2010, 2016; Vittecoq et al., 2016), the current study examined the occur- and resistance to this antimicrobial has already been detected for rence of AMR in one of the most fast expanding species, with wild boar (Reinhardt et al., 2018; Zottola et al., 2013). Resistance increasing impacts and contact with humans, at a broader spatial to cephalosporins (mostly cefotaxime), fluoroquinolones and line- scale, the European continent. Other studies have also showed zolid has also been reported in Italy, Serbia, Czech Republic and the reliability of using other wildlife species as important sentinels Portugal (Literak et al., 2010; Sousa et al., 2017; Velhner et al., for AMR [(for example, small mammals (Furness et al., 2017)] but 2018; Bonardi et al., 2019). This is of special importance since these wild boar close interaction with humans and livestock, their represent ‘‘critically important antimicrobials for human med- omnivorous behavior and large home ranges, and their consump- icine” (WHO, 2019). These results highlight the possible direct tion through hunting harvest, could favor dissemination of antimi- and indirect routes of transmission of antibiotic-resistant bacteria crobial resistance to the wider environment. In fact, once wild boar in the human-livestock-wildlife interface. is exposed, through various sources, to foreign commensal and The epidemiology of resistance genetic markers has also been antibiotic resistant microorganisms that have the potential to investigated. Worryingly, cross-talk with the microbiota of the species, creating a window extended spectrum beta-lactamases (ESBL)-producing E. coli of opportunity for cross selection and clonal spread of tolerant bac- isolates have been isolated from samples of wild boar in Portugal teria, it potentially becomes a significant carrier and disperser of (Poeta et al., 2009), Italy (Bonardi et al., 2019), Slovenia (Križman AMR, originating the risk of ecological spread as it moves between et al., 2017) and the Czech Republic (Literak et al., 2010). The class the different compartments (urban – semi-natural – natural). of beta-lactamases antibiotics (e.g. penicillin) is amongst the most While the studies used in this review did not define exposure important group of antimicrobial agents used in human and veteri- paths and transmission routes, most of them suggested that the nary medicine. The detection of ESBL-producing E. coli in wildlife level of resistant bacteria detected in wild boar seems to be related was firstly reported in 2006 (Costa et al., 2006) and since then it with the degree of association with human activity (Skurnik et al., has been isolated from livestock, food and environmental samples, 2006). Different studies showed that wildlife populations living in in different European countries (Poeta et al., 2009). In fact, ESBL- close proximity to humans or agricultural areas exhibit higher producing E. coli are now frequently found in wildlife (Guenther levels of resistance than those living in more remote or natural et al., 2011), particularly in birds and mammals (Silva et al., areas (Allen et al., 2010). For example, E. coli isolates from small 2011; Gonçalveset al., 2012). For example, Simões et al. (2010) mammals living on swine farms in Canada have higher rates of found that amongst the E. coli isolates from wild seagull faeces, resistance than E. coli isolates from natural areas (Kozak et al., 32% displayed an ESBL phenotype, which could be related to 2009) and African baboons in contact with humans harbour more human waste. The variants of ESBLs already reported in wild boar antibiotic-resistant bacteria than those in remote areas (Rwego include blaCTX-M-1, blaTEM1-b and blaTEM-52b (Bonardi et al., 2019; et al., 2008). Contrastingly, other studies showed the occurrence Literak et al., 2010; Poeta et al., 2009). In fact, some of the above- of multidrug-resistant bacteria in remote places therefore under- mentioned studies reported a high number of ESBL isolates from lining the complexity of the spread of antimicrobial resistance in wild boars contained the blaCTX-M-1 gene. CTX-M-1 gene is one of wild animals (Sjölundet al., 2008). Whereas this process is difficult most prevalent ESBLs in Europe. It has been frequently detected to disclose mechanistically, advances in genetic and phylogenetic in humans (Novais et al. 2007) as well as in food-producing ani- analyses, and also in whole-genome sequencing, have facilitated mals (Meunier et al. 2006). ESBL-producing E. coli with blaCTX-M-1 the detection of AMR genes, linking cases, defining exposure paths has also been detected in wild birds (Poeta et al. 2008; Dolejska and transmission routes, enabling the deduction of clonal relation- et al., 2009). ships and the unfolding of hypotheses concerning AMR amplifica- The reviewed studies showed that resistance to tetracyclines in tion. For example, by performing phylogenetic analysis, Ward et al. E. coli is mainly encoded by tetA, tetB and tetG genes (Caleja et al., (2014) showed that livestock was an important source of Staphylo- 2011; Literak et al., 2010) or by tetM, tetS and tetK in Gram-positive coccus aureus clonal complex 398 (CC398) in humans while Mather bacteria (Guerrero-Ramos et al., 2016; Poeta et al., 2007b). Resis- et al. (2011) reported that sympatric animals are improbable to be tance to tetracycline had also been recovered from E. coli isolates the main cause of Salmonella Typhimurium DT104 (DT104) in from small wild mammals in Poland (Swiecicka et al. 2003) and humans and that other sources of infections must be relevant. in Germany (Guenther et al. 2010). Interestingly, mecA resistance genes, which are commonly carried by methicillin-resistant Sta- phylococcus aureus (MRSA) were also found in some wild boar pop- 4. Conclusions and future perspectives ulations. MRSA is an important pathogen for humans, causing severe and hard to treat diseases in hospitals and in the commu- Following this line, future steps should try to unveil the role of nity because of it is ease dissemination and multiresistance against wild boar as reservoirs and amplifiers of AMR and the likely several antimicrobials, thefore is considered a public health con- sources and mechanisms of persistence of AMR in this species. cern due to the limited options for treatment. MRSA detection in Thus, to fully understand the AMR pressures exerted on wild boar wildlife (e.g., Eurasian griffon vulture, Iberian ibex, red deer, and populations, it is important to continuously monitor resistance wild boar) in Spain has revealed a very low prevalence but geno- trends at sites that differ in exposure levels and to detect transfer types were related to livestock and humans (Porrero et al., 2014). of resistant bacteria or resistance genes from animals to humans Some of the resistance genes described in this study, have been and vice versa (Martel et al., 2001). associated with mobile genetic elements such as conjugative plas- The studies analysed raise several concerns regarding the role of mids, transposons or integrons. These elements play an important wild boars as carriers, reservoirs and dispersers of AMR and AMR role in horizontal gene transfer, which has been responsible for the strains into the environment, but they are mainly descriptive. dissemination of antimicrobial resistance throughout diverse bac- Future studies most go beyond their descriptive nature and focus terial species (Barlow, 2009). on understanding the role that anthropogenic activities may play Overall, this review emphasizes that AMR is no longer an issue on AMR in wild boar and wildlife in general. AMR research has confined to the livestock and human settings in Europe, but is been mainly focused on providing prevalence reference values R.T. Torres et al. / Science of the Total Environment 717 (2020) 135001 7 and identifying resistance patterns, even though the knowledge on 2020). We would like to thank University of Aveiro (Department of how landscape drives AMR in wild and domestic hosts could fur- Biology) and FCT/MEC for the financial support to CESAM RU (UID/ ther the understanding regarding AMR dissemination in the envi- AMB/50017) through national funds, co-financed by the FEDER, ronment (Singer et al., 2006). With this in mind, we recommend within the PT2020 Partnership Agreement. the application of an ecological approach to AMR dynamics, with ecological tools contributing to the disclosure of the origins and transmission routes of AMR in the wildlife-livestock compartment Appendix A. Supplementary data with contrasting human influence in order to optimize the resources towards AMR management at a larger scale. 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