Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), is not only one of the most common etiological factors of human infectious disease but also a pathogen with a profound impact on animal welfare because of increasing antibiotic resistance and the resulting economic burden [1,2]. The first reports concerning MRSA date back to the years 1959–1960, when it evolved from a susceptible S. aureus strain as a result of the implementation of methicillin as a new antimicrobial drug in hospitals. Additionally, the first observations suggested that it originated from one epidemic clone as all investigated strains exhibited the same antimicrobial resistance profile (penicillin, streptomycin, and tetracycline), [3]. Described by the Centers for Disease Control and Prevention as an note-threating microorganism quickly acquiring antibiotic resistance, MRSA gradually spread around the world, resulting in a high epidemiological burden both for humans as well as animals [4]. The strains are all characterized by the presence of an acquired type of resistance to β-lactam antibiotics encoded by genes from the mec group (mecA, mecB, and mecC) located in the staphylococcal chromosomal cassette (SCCmec). Genes encode for novel types of the penicillin-binding protein exhibiting decreased affinity to β-lactams resulting in inactivation of an antibiotic [5]. Depending on the setting, where the MRSA infection has been first reported, strains are divided into certain subpopulations. For human infections, the most prevalent hospital-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA) inform as to whether the strains were isolated in a nosocomial environment or outside, respectively. The third subpopulation—animal-associated MRSA (AA-MRSA), sometimes limited only to livestock-associated-MRSA (LA-MRSA)—includes pathogens isolated from animals [6,7]. The determination of subpopulation type can be helpful in epidemiological investigation by providing information about certain MRSA clone origins; however, the dynamic spread and transmission of MRSA worldwide blur the formerly clear line between clones of human and animal origin.

Since first MRSA was discovered, it has consequently gained resistance to other classes of antibiotics, like macrolides and tetracyclines, or chemotherapeutics, like fluoroquinolones, resulting in difficulties in the development of successful antimicrobial therapy in infected individuals [8]. While even more health-threatening S. aureus strains have emerged, including vancomycin-resistant S. aureus (VRSA) often characterized by multi-drug resistance, MRSA still remains the main therapeutic challenge worldwide [9]. Depending on the character and location of infection, routine antimicrobial therapy of MRSA infections consists of the application of several antimicrobial drugs, i.e., vancomycin in the case of MRSA bacteremia, daptomycin in the treatment of soft-tissue infections, or mupirocin for skin infections. For infections caused by multi-drug-resistant strains, novel antimicrobial agents are often applied, e.g., linezolid antibiotic, or multiple semisynthetic drugs, such as tigecycline, dalbavancin, oritavancin, iclaprim, cethromycin, or delafloxacin [10]. Except standard antibiotic therapy, alternative treatments and agents supporting antibiotic therapy are being developed as a new approach for the treatment of MRSA infections. The above-mentioned strategies consist of combining known antimicrobial agents with substances or compounds of natural origin or the application of a combination of two or more antimicrobial agents [8]. In spite of all these efforts, the emergence of resistance to new antimicrobials is being observed. MRSA strains resistant to daptomycin were described just years after the official Food and Drug Administration approval for the treatment of S. aureus in 2006. A similar situation has been noted for linezolid, implemented for treatment in the year 2000, to which resistance was first described in 2005. Since then, S. aureus has developed several resistance mechanisms [11].

The growing antibiotic resistance to so called “last resort” antibiotics in the treatment of serious bacterial infections drastically limits the current therapeutic options. There are several factors that increase the risk of acquiring antibiotic resistance in bacteria. They include: the excessive use of antimicrobial agents creating selective pressure enabling resistance to develop and persist in the environment, the emergence of novel sources of drug-resistant bacteria as well as novel routes for these bacteria to spread which allows not only the direct transmission of MRSA but also the occurrence of the horizontal transfer of resistance factors [12]. In the recent years, animals have become a profound secondary source of MRSA in the environment, and the frequent contact between animals and humans create a significant route of their transmission [13]. Therefore, to further fight antibiotic resistance in S. aureus, it is indispensable to investigate and understand novel reservoirs of antibiotic-resistant bacteria and the evolutionary consequences of their global spread. The epidemiology of MRSA is changing dynamically due to intensive circulation within the community and farming environment [14]. However, the transfer of microorganisms between humans and animals seems to be a part of the natural process of microbial adaptation. The interspecies transmission of antibiotic-resistant bacteria raises significant concerns for public health. The prevalence and risk factors for colonization and subsequent infection with multidrug-resistant microbes among humans are well established when compared with animal populations [15]. MRSA colonizes and infects companion animals and wild animals as well as livestock, causing serious diseases of worldwide significance, e.g., in poultry or dairy cows [16].

2. Methicillin-Resistant Staphylococcus aureus in Companion Animals

The human population is steadily expanding into new geographical areas, which together with the increase in the number of large-scale animal farms generates new transmission pathways that ease the spread of MRSA in the environment. High MRSA colonization rates in livestock farming environments and the emergence of LA-MRSA in humans raise questions regarding its origin and possible transmission pathways [49]. Similar to companion animals, MRSA colonizing livestock can act as a significant reservoir for drug-resistance genes. The transmission of these genes is a significant epidemiological concern, because of the possible share in acquiring MRSA that colonizes humans. The high diversification of LA-MRSA isolation rates and their genetic variants in animal farming environments is common and clearly seen in studies from different parts of the world.

Researchers suggest that the current spread of LA-MRSA in Europe is connected to the international pig market [50]. What is more, the prevalence of LA-MRSA in pigs is rising constantly, with ST398 LA-MRSA lineage domination observed in most European countries [51,52]. Despite this, the epidemiological situation in other parts of the world differs. The domination of certain lineages of LA-MRSA in livestock farming environments is being observed (Table 2). The distribution of MRSA sequence types among livestock depends not only on geographical location [53,54] but also the major clonal lineages causing infections in humans, e.g., in Australian piggeries, as many as 84% of MRSA strains were classified as ST93—the most common CA-MRSA in the country. Additionally, MRSA isolation rates were high and accounted for 76% in animals and 60% in pig farm workers [55].

Staphylococcus aureus remains a major etiological factor of bovine mastitis [67,68], and it is estimated that methicillin-resistant strains are responsible for approximately 12% of infections [69,70]. Recent findings confirm that MRSA strains circulating among humans are capable of causing infection in cows [71]. Juhász-Kaszanyitzky et al. found that subclinical mastitis in cows on a Hungarian farm was caused by MRSA genetically undistinguishable from a strain isolated from a farm worker. Moreover, an alarmingly high percentage of MRSA strains isolated from dairy cows harbor multiple enterotoxin genes simultaneously (seg, sei, sem, sen, seo, and seu), making a possible outbreak from contaminated milk more health-threatening to humans [61].

Methicillin-resistant strains are also present in poultry [49,57,58,72] and poultry-derived products [73,74]. In some countries, the prevalence of MRSA among poultry has been found to be relatively high. In Algeria, as many as 57% of laying hens and 50% of broiler chickens were found to be colonized with MRSA. The authors also found that the poultry were significantly more often colonized than the bovine animals (31%), [49]. The poultry were found to be colonized not only by livestock-associated CC398 but also by strains of human origin [58]; thus, the epidemiological situation regarding poultry market should be carefully monitored in order to limit the spread of virulent MRSA strains in the environment.

In comparison to the environment of large-scale farms with bovine, swine or poultry, the epidemiology of S. aureus differs in small dairy-ruminant herds. Carfora et al. observed low intra-farm prevalence of both MSSA and MRSA among sheep. In total, 2.16% of milk samples were found S. aureus positive and only 0.34% MRSA positive, however, genotyping revealed that all MRSA collected from animals and farm workers belonged to the same MLST variant (ST1), [75]. MRSA is also being isolated from goats. Loncaric et al. described a case of necropsy in a goat caused by LA-MRSA ST398. The same strain was isolated earlier from the goat’s owner, proving the infectious potential of LA-MRSA transmitted from the human host to the animal [76]. In the Czech Republic, LA-MRSA ST398 was isolated on a goat farm, both from animals and personnel, indicating circulation of S. aureus in a given environment; however, the authors did not detect any MRSA strains among sheep and pig farms in the same homestead [62]. The presence of MRSA was also found in rabbits; S. aureus was detected both as a colonizing agent as well as an etiological factor causing lesions. Large-scale studies in commercial rabbitries located on the Iberian Peninsula revealed the presence of MRSA in 19 out of 89 farms with an 11.25% colonization rate among rabbits [63].

The presence of MRSA in the large-scale farming environment challenges current epidemiological approaches limiting the circulation of pathogens between animals and humans. Moreover, it increases the probability of the emergence of new pathogenic microorganisms, making agro-ecosystems a global threat to public health.