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

Abstract

Mobile genetic elements (MGEs) often carry genes that benefit their bacterial hosts. In methicillin-resistant Staphylococcus aureus (MRSA), MGEs have been associated with antibiotic resistance, virulence, and host adaptation. Clonal-complex (CC) 398 is the dominant MRSA in European livestock, and a growing cause of human infections. To understand the risk posed by livestock-associated MRSA to human health, we have used a collection of 1,180 CC398 genomes, sampled from several livestock species and humans, with a broad geographic distribution and spanning 27 years, to reconstruct the dynamics of the MGEs. 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 vertically inherited for 57 years. This was followed by the acquisition of a large SCCmec type V element that carries methicillin, tetracycline and heavy metal resistance genes. This has been maintained within livestock-associated CC398 for at least 35 years, with occasional truncations and replacements with other, smaller type IV SCCmec elements. In contrast, a class of prophages that carry a human immune-evasion gene cluster, that are largely absent from livestock-associated CC398, have been repeatedly gained and lost across both human- and livestock-associated CC398. The variable dynamics of these three MGEs means that when livestock-associated MRSA infects humans, re-adaptation to the human host outpaces the loss of antibiotic resistance. Moreover, the stability of both Tn916 and SCCmec suggests that they may persist despite ongoing reductions in antibiotic and zinc oxide use in farming.

Absence ofStaphylococcus aureusin wild populations of fish supports a spillover hypothesis

“…Our results therefore suggest that the presence of S. aureus in this aquaculture environment is due to recent spillover from human populations. This is consistent with another study that showed the presence of a CC398 MSSA isolate from a gilthead seabream (35), which most likely originated from a human-associated lineage of CC398 (22,36,37). S. aureus have been recovered from municipal (65–68), hospital (69), and agricultural wastewaters/sewage (70), representing potential sources of human environmental contamination.…”

“…Only one study by Salgueiro et al . (2020), performed genome sequencing and found CC398 methicillin-sensitive S. aureus (MSSA) (35), most likely human-associated (22,36,37). This study suggests that S. aureus is present in fish due to spillover from human populations but does not have the discrimination to test whether there is adaptation and persistence of S. aureus within fish populations or aquatic environments.…”

“…Supporting this conjecture, S. aureus has also been found in fish sampled directly from aquaculture, where fish processing and handling is limited and MRSA have been identified in cagecultured tilapia in Malaysia (32), tank cultured dusky kob in South Africa (33), and farmed fish in Iran (34). Only one study by Salgueiro et al (2020), performed genome sequencing and found CC398 methicillin-sensitive S. aureus (MSSA) (35), most likely human-associated (22,36,37). This study suggests that S. aureus is present in fish due to spillover from human populations but does not have the discrimination to test whether there is adaptation and persistence of S. aureus within fish populations or aquatic environments.…”

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.…”

A review of new emerging livestock-associated methicillin-resistant Staphylococcus aureus from pig farms

“…Using molecular typing with multi-locus sequence typing, MRSA clones found in pigs have been classified as clonal complex 398 (CC398) with sequence type 398 (ST398) [5]. In pigs, LA-MRSA is becoming increasingly resistant to several antibiotics commonly used in livestock, such as tetracycline, aminoglycoside, trimethoprim, and penicillin [6,7].…”