Livestock origin for a human pandemic clone of community-associated methicillin-resistant Staphylococcus aureus

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.

Importance: Animals are the major source of new pathogens affecting humans. However, the potential for pathogenic bacteria that originally were found in animals to switch hosts and become widely established in human populations is not clear. Here, we report the discovery of emergent clones of methicillin-resistant Staphylococcus aureus (MRSA) that originated in livestock and switched to humans, followed by host-adaptive evolution and epidemic spread in global human populations. Our findings demonstrate that livestock can act as a reservoir for the emergence of new human bacterial clones with potential for pandemic spread, highlighting the potential role of surveillance and biosecurity measures in the agricultural setting for preventing the emergence of new human pathogens.

FIG 1

Identification of human epidemic S. aureus clones descended from bacteria that made livestock-to-human host jumps. The Bayesian phylogenetic reconstruction of the CC97 lineage is shown. The tree is based on core genome alignment with branches color coded according to the host species association (blue, bovine; green, porcine; orange, caprine; red, human) and date and country of origin of each isolate indicated. The presence or absence (−) of β-toxin phage IEC variants B and E and SCCmec type IV or V is indicated by the appropriate letter, and the presence of S. aureus pathogenicity island (SaPI)-encoded vwb or phage-encoded lukM/lukF is denoted by black and gray circles, respectively. The branch lengths are scaled according to the time scale bar (years) and the posterior probability values are indicated at each node. Clades A and B are shown.