Abstract
The importance of livestock as a source of bacterial pathogens with the potential for epidemic spread in human populations is unclear. In recent years, there has been a global increase in community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections of healthy humans, but an understanding of the different evolutionary origins of CA-MRSA clones and the basis for their recent expansion is lacking. Here, using a high-resolution phylogenetic approach, we report the discovery of two emergent clones of human epidemic CA-MRSA which resulted from independent livestock-to-human host jumps by the major bovine S. aureus complex, CC97. Of note, one of the new clones was isolated from human infections on four continents, demonstrating its global dissemination since the host jump occurred over 40 years ago. The emergence of both human S. aureus clones coincided with the independent acquisition of mobile genetic elements encoding antimicrobial resistance and human-specific mediators of immune evasion, consistent with an important role for these genetic events in the capacity to survive and transmit among human populations. In conclusion, we provide evidence that livestock represent a reservoir for the emergence of new human-pathogenic S. aureus clones with the capacity for pandemic spread. These findings have major public health implications highlighting the importance of surveillance for early identification of emergent clones and improved transmission control measures at the human-livestock interface.
Generated Summary
This research article reports on the discovery of emerging clones of methicillin-resistant Staphylococcus aureus (MRSA) that originated in livestock and subsequently spread to human populations. The study employed a high-resolution phylogenetic approach to investigate the evolutionary history of the CC97 S. aureus lineage, a leading cause of bovine mastitis in Europe, Asia, and the Americas. The researchers analyzed 220 S. aureus isolates of CC97 from bovine, human, porcine, and caprine hosts, collected between 1956 and 2012 across 18 countries. The analysis included whole-genome sequencing of 43 CC97 strains and phylogenetic reconstruction using the BEAST program. The study aimed to identify clones that are epidemic in human populations and evolved through host jumps from cows, highlighting the role of livestock as a potential reservoir for new human-pathogenic S. aureus clones.
Key Findings & Statistics
- In Denmark, cases of MRSA caused by CC97-related spa types increased from 2 in 2007 to 22 in 2011, representing an 11-fold increase in 5 years (P < 0.01).
- Human CC97 clade A consists of isolates from 12 different countries on four continents.
- The study estimated the host jump events occurred between 1894 and 1977 for human CC97 clade A and between 1938 and 1966 for human CC97 clade B.
- The most recent minimum date for the host jump event using MLST data was estimated.
- 7 of 17 bovine isolates were sensitive to all antimicrobial agents tested.
- 20 of 23 human isolates were resistant to at least one antimicrobial agent.
- Human CC97 clade A: 14 out of 16 isolates had IEC containing genes sak and scn (IEC type E).
- Human CC97 clade B: 4 out of 8 isolates had an IEC containing genes sak, chp, and scn (IEC type B), and one isolate had an IEC type E.
Other Important Findings
- The study identified two emergent clones of human epidemic CA-MRSA that resulted from independent livestock-to-human host jumps by the bovine S. aureus complex, CC97.
- One of the new clones was isolated from human infections on four continents, demonstrating global dissemination since the host jump occurred over 40 years ago.
- The emergence of human S. aureus clones coincided with the independent acquisition of mobile genetic elements encoding antimicrobial resistance and human-specific mediators of immune evasion, suggesting an important role for these genetic events in survival and transmission among human populations.
- The phylogenetic tree resolved S. aureus CC97 into distinct host-associated clades.
- The majority of livestock-associated CC97 isolates are basal to the human clades.
- Methicillin resistance is a characteristic of the human CC97 clades, with two distinct SCCmec types (IV and V).
- The earliest human isolate identified in clade B (1980) was sensitive to all antibiotics, while all other clade B isolates (since 2005) were resistant to multiple antimicrobials.
- The antimicrobial susceptibility profiles of human and pig CC97 isolates showed resistance to a greater number of antimicrobials than bovine CC97 S. aureus.
- Of the 20 livestock isolates, 3 and 8 isolates contained MGE encoding the LukM/F leukotoxin and the von Willebrand binding protein (vWbp), respectively.
- None of the human isolates contained livestock-associated MGE.
Limitations Noted in the Document
- The study acknowledges that surveillance systems for other countries are currently inadequate to identify trends in S. aureus genotypes associated with human infections.
- The study’s reliance on MLST has precluded rigorous examination of the occurrence of more-recent livestock-to-human host jump events.
- The authors mention that the dairy industry does not strongly promote the emergence of antibiotic-resistant S. aureus. However, they note that this observation might reflect the ability of bovine strains to invade and survive within bovine mammary epithelial cells.
Conclusion
The study’s findings demonstrate that livestock can act as a reservoir for the emergence of new human bacterial clones, with the potential for pandemic spread, emphasizing the need for surveillance and biosecurity measures in agricultural settings. The research underscores the importance of hygiene in preventing the hospital transmission of nosocomial pathogens like MRSA, which has seen reductions due to improved hygiene measures. The study suggests that controlling the spread of bacterial flora between livestock and humans might limit opportunities for livestock-to-human transmission. The study’s data support the idea that the ongoing surveillance of livestock and humans may help identify emergent clones, thus decreasing the disease impact. The findings have significant implications for public health, highlighting the need for early identification of emergent clones and improved transmission control measures at the human-livestock interface. These data demonstrate that livestock represent a potential reservoir of pathogenic bacteria that may cross the species barrier and spread among global human populations. Furthermore, the data suggest that a limited number of genetic events may be sufficient to transform an S. aureus strain which has coevolved with bovine hosts over several thousand years into a successful human epidemic lineage.