Stable antibiotic resistance and rapid human adaptation in livestock-associated MRSA

Abstract

Mobile genetic elements (MGEs) are agents of horizontal gene transfer in bacteria, but can also be vertically inherited by daughter cells. Establishing the dynamics that led to contemporary patterns of MGEs in bacterial genomes is central to predicting the emergence and evolution of novel and resistant pathogens. Methicillin-resistant Staphylococcus aureus (MRSA) clonal-complex (CC) 398 is the dominant MRSA in European livestock and a growing cause of human infections. Previous studies have identified three categories of MGEs whose presence or absence distinguishes livestock-associated CC398 from a closely related and less antibiotic-resistant human-associated population. Here, we fully characterise the evolutionary dynamics of these MGEs using a collection of 1180 CC398 genomes, sampled from livestock and humans, over 27 years. We find that the emergence of livestock-associated CC398 coincided with the acquisition of a Tn916 transposon carrying a tetracycline resistance gene, which has been stably inherited for 57 years. This was followed by the acquisition of a type V SCCmec that carries methicillin, tetracycline, and heavy metal resistance genes, which has been maintained for 35 years, with occasional truncations and replacements with type IV SCCmec. In contrast, a class of prophages that carry a human immune evasion gene cluster and that are largely absent from livestock-associated CC398 have been repeatedly gained and lost in both human- and livestock-associated CC398. These contrasting dynamics mean that when livestock-associated MRSA is transmitted to humans, adaptation to the human host outpaces loss of antibiotic resistance. In addition, the stable inheritance of resistance-associated MGEs suggests that the impact of ongoing reductions in antibiotic and zinc oxide use in European farms on livestock-associated MRSA will be slow to be realised.

Prevalence, antimicrobial resistance, and staphylococcal toxin genes of blaTEM‐1a‐producing Staphylococcus aureus isolated from animals in Chongqing, China

“…Although the isolation rate of MRSA was low in our isolates, other isolates showed significant resistance to penicillins. Therefore, the prevalence of LA‐MRSA might be much higher in the future because of selective pressures (Matuszewska et al., 2022 ). Because LA‐MRSA might function as a reservoir for MRSA that can infect people (Fessler et al., 2011 ; Li et al., 2017b ; Loncaric et al., 2013 ; Loncaric & Künzel, 2013 ), we suggest regular longitudinal surveillance of MRSA in livestock animals, especially pigs and chickens.…”

Low-level colonization of methicillin-resistant Staphylococcus aureus in pigs is maintained by slowly evolving, closely related strains in Finnish pig farms

“…All strains harboured SCCmec subtype Vc(5C2&5). This was the dominant SCCmec subtype in LA-MRSA CC398 in two studies including sequences from several European countries [54,55]. SCCmec Vc(5C2&5) is known to carry heavy metal resistance gene crzC and tetracycline resistance gene tet(K) in addition to mecA.…”

“…SCCmec Vc(5C2&5) is known to carry heavy metal resistance gene crzC and tetracycline resistance gene tet(K) in addition to mecA. It has been suggested that the use of zinc oxide in pig production may have favoured the selection of strains carrying SCCmec Vc [55]. The effects of an EU-wide ban on zinc oxide in pig husbandry as of 26 June 2022 on the prevalence of LA-MRSA CC398 remain to be seen.…”

Genome sequencing and comparative genomic analysis of bovine mastitis-associated Staphylococcus aureus strains from India

“…The major virulence factors and AMR genes are localized on mobile genetic elements (MGEs). A recent report suggested that CC398, the dominant livestock-associated MRSA in Europe, rapidly adapted to cause human infections [ 25 ]. Due to the clonal expansion, S .…”

“…The major virulence factors and AMR genes are localized on mobile genetic elements (MGEs). A recent report suggested that CC398, the dominant livestock-associated MRSA in Europe, rapidly adapted to cause human infections [25]. Due to the clonal expansion, S. aureus strains belonging to the same CC have specific virulence gene signatures [26,27] and restriction-modification systems that reduce HGT between different S. aureus lineages [28,29].…”