For example, mutations leading to loss of function have occurred in genes encoding a putative surface-exposed lipoprotein, a protease SspA involved in the maturation of SspB that contributes to blood clot formation (17), andasp1required for the surface expression of SraP, a cell wall-associated protein involved in the pathogenesis of infective endocarditis (18). have decided the evolutionary history of a Satraplatin major new animal pathogen that has undergone rapid avian host adaptation and intercontinental dissemination. These data provide a new paradigm for the impact of human activities on the emergence of animal pathogens. Keywords:evolution, host adaptation, pathogen, phylogeography, globalization Globalization and the pattern toward the integration of trade of crops and livestock could have a major impact on the emergence and dissemination of pathogens. Shifts in agricultural practice result in opportunities for pathogens to expand into new host species and to spread rapidly to new territories. For example, the epidemics of bovine spongiform encephalitis (1) and the foot and mouth disease epidemic (2) were caused by changing agricultural practices providing new opportunities for transmission, including the use of meat and bone meal in cattle feed, and the long-distance transport of livestock, respectively. The broiler poultry industry has been transformed within the last 50 years from a market dominated by smallholder chicken farms to a multibillion dollar industry controlled by a handful of multinational companies who supply a limited number of breeding lines to a global market (3,4). Infectious diseases of chicken flocks are a major economic burden around the industry. In particular,Staphylococcus aureusis associated with several infections of poultry including septic arthritis, subdermal abscesses (i.e., bumble foot), and gangrenous dermatitis (5). In the 1970s, a new form ofS. aureusinfection of broiler poultry known as bacterial chondronecrosis with osteomyelitis (BCO) was described Satraplatin (6). Since then, BCO has increased in frequency to become a leading cause of lameness in the broiler chicken industry (7,8). The reasons for the emergence and subsequent increase in incidence of BCO among chickens are unknown. == Results and Discussion == == The Majority ofS. aureusIsolates from Poultry Belong to a Single Clonal Complex (CC5) Usually Associated with Humans. == To examine the population genetics ofS. aureusstrains infecting farmed birds, we carried out multi-locus sequence typing (MLST) of 57S. aureusisolates, including 48 isolates from healthy and diseased poultry, in 8 countries on 4 continents isolated in the past 54 years, in addition to 9 isolates from different species of reared game and wild birds [supporting information (SI) Table S1]. Remarkably, the majority of all avian isolates (n= 35; 61%) including 32 (67%) from broiler chickens, belonged to a single sequence MGC102762 type (ST), ST5, or its single locus variants (ST1342, ST1346, and ST1350), including isolates from all countries examined except Australia (Fig. 1). The clonal complex CC5 (which includes related haplotypes differing at a small number of loci) is one of the most successful human-associated lineages ofS. aureus, characterized by its global distribution and frequent emergence of methicillin-resistant strains (9). Of the non-CC5 isolates identified, which included isolates from broiler chickens, reared bird species such as pheasant and partridge, and a wild buzzard, 11 belonged to an unrelated clonal complex, CC385, which has not been identified previously among human or mammalian Satraplatin strains. The lack of association of CC385 with humans or other mammals and its wide distribution among an array of reared and wild bird species in different countries suggests that the CC385 lineage has had a long-term avian host restriction (Table S1). Of the remaining 11 isolates, 4 from Australia belonged to a novel ST1345, 3 Japanese isolates were ST1027, 2 were of ST8, and single isolates were of ST1 and ST15, all being related or identical to STs previously identified among humanS. aureusisolates (Fig. 1AandB). == Fig. 1. == The majority of poultryS. aureusisolates evolved by a single host jump from humans followed by wide dissemination. (A) Geographical distribution of poultry and other avianS. aureusSTs identified in countries from 4 different continents. Pie chart diameter is proportional to the number of isolates from each location. (B) Neighbor joining tree with bootstrapping consensus inferred from 500 replicates was constructed using concatenated sequences ofS. aureusSTs from birds (green branches) and representatives of the major clonal complexes of human and animal origin in theS. aureusspecies (black branches). The 2 2 major avian-associated clonal complexes, CC5 and CC385, are indicated in blue and red, respectively. (C) Minimum spanning.