WILDLIFE, SUPERBUGS AND MULTIDRUG RESISTANCE
Although wildlife species are not typically treated with antibiotics in free-range habitats, many animals have acquired antibiotic-resistant bacteria (Johnson et al. 1998; Osterblad et al.
2001; Hernandez et al. 2007; Literak et al. 2010; Carroll et al. 2015; Alonso et al. 2016; McDougall et al. 2021a). Environmental contamination with antibioticresistant bacteria from humans and domestic animals (companion and production species) facilitates transmission to wildlife, with water being the most significant vector for transmission (Perry and Wright 2013; Marti et al. 2014).A plethora of bacterial species carry some form of antibiotic resistance, but those that are multidrug-resistant present significant concern for global health. The term ‘superbug’ is applied to bacteria that are highly resistant to the various antibiotic classes used for treatment of the diseases they cause. ‘Superbugs’ tend to have multiple mechanisms to overcome inhibitory actions of multiple antibiotics and mostly represent pathogenic strains of commensal bacteria. Examples of ‘superbugs’ are vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), extended spectrum β-lactamase (ESBL) producing Enterobacterales and carbapenem-resistant Enterobacterales (CRE), carbapenem-resistant Acinetobac- ter baumannii (CRAB) and fluoroquinolone-resistant Salmonella typhi. Many of these ‘superbugs’ have been listed by the World Health Organization as pathogens for which we urgently require new treatments and strategies to prevent and control antimicrobial resistance (WHO 2024). Initially, these ‘superbugs’ were of nosocomial concern (hospital- acquired infections), but representative clonal strains are emerging globally, and community-acquired infections are now apparent. The distribution of multidrug-resistant (MDR) bacteria now far exceeds human hosts and human clinical settings and all ‘superbugs’ now persist in the environment.
The increasing isolation of MDR strains from wildlife sources demonstrates the far-reaching distribution of antibiotic-resistant bacteria. The spread and persistence of some ‘superbugs’ and the genetic machinery that enable resistance have been proposed as anthropogenic environmental pollutants (Guenther et al. 2011; Gillings et al. 2014).2.1 Multidrug-resistant strains
Several MDR bacterial species currently have a global distribution while others are rapidly emerging. Initially a hospital-acquired infection, MRSA is now community- acquired (Conly and Johnston 2003) and resistant to multiple β-lactam antibiotics (Hiramatsu et al. 2001).
Enterococci resistant to vancomycin (VRE), first described in the United Kingdom in 1988 (Moellering 1992), comprise five VRE genotypes: vanA-vanE (Conly and Johnston 2003).
Gram-positive and gram-negative bacterial species resistant to extended spectrum β-lactams have also emerged. The extended spectrum β-lactams include cephalosporins and carbapenems. Select ESBL-producing lineages from different bacterial species are emerging globally, e.g. Escherichia coli sequence type 131 (ST131), which now includes strains with acquired fluoroquinolone resistance in addition to cephalosporin resistance (Platell et al. 2011; Ben Zakour et al. 2016).
Of recent concern is the emergence of CRE, which were discovered in 1996 (Munoz-Price et al. 2013). This group includes strains of E. coli, Klebsiella pneumoniae, K. oxytoca, Enterobacter aerogenes and E. cloacae that are resistant to the carbapenem antibiotics. The global emergence of CREs has been attributed to K. pneumoniae ST258 (Nordmann et al. 2011). The prevalence of CRE in Australia is increasing, with the number of reported CRE clinical isolates increasing from 829 in 2022 to 1205 in 2023 (a relative change of 45.4%) (ACSQHC 2024).
2.2 Antibiotic-resistance machinery
The genetic machinery associated with horizontal transfer of antibiotic resistance has been integral to the evolution of bacteria (Mazel 2006).
Mobile genetic elements such as plasmids, transposons and integrons facilitate the exchange of resistance genes within and between different bacterial species (Gillings 2017).One mobile genetic determinant of resistance, the clinical class 1 integron, has been central to the emergence of resistance, having been assembled under selection pressure of antibiotic use (Gillings et al. 2008). The Class 1 integron’s genetic components facilitate acquisition and expression of multiple resistance genes, generating multiple resistance traits, particularly in Gram-negative bacteria. Clinical class 1 integrons are highly abundant in pathogenic and non-pathogenic enteric bacteria from humans and farm animals, with prevalence estimates as high as 80% (Gillings 2017). The passing of enteric bacteria in faeces has led to substantial environmental loading of bacteria carrying class 1 integrons, with sewage, wastewater and direct environmental contamination from farm animal faeces being sources (Gillings 2017).
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