Figure 1. Infection-causing S. aureus form closely related but distinct populations descended from nose-colonizing bacteria in the majority of infections.

Bacteria sampled from the nose and infection site of 105 patients formed one of three population structures, illustrated with example haplotrees: (A) Unrelated populations differentiated by many variants. (B) Highly related populations separated by few variants. (C) Highly related populations with one genotype in common. Reconstructing the ancestral genotype in each patient helped identify the ancestral population: (D) Nose-colonizing bacteria ancestral. (E) Ambiguous ancestral population. (F) Infection site bacteria ancestral. (G) Phylogeny illustrating the working hypothesis that variants differentiating highly related nose-colonizing and infection-causing bacteria would be enriched for variants that promote, or are promoted by, infection. In A–F, haplotree nodes represent observed genotypes sampled from the nose (white) or infection site (grey), with area proportional to genotype frequency, or unobserved intermediate genotypes (black). Edges represent mutations. Patient identifiers and sample sizes (n) are given. In A–G, edge color indicates that mutations occurring on those branches correspond to B-class variants between nose-colonizing and infection-causing bacteria (blue), C-class variants among nose-colonizing bacteria (gold) or D-class variants among infection-causing bacteria (red). Black dashed edges indicate ancestral lineages. A B C.

Figure 1—figure supplement 1. Distribution of the number of variants identified within 105 severely infected patients, by class.

Three classes of variants were identified: those representing genuine differences between nose-colonizing and infection populations (B-class), variants specific to the nose-colonizing population (C-class) and variants specific to the disease-causing infection population (D-class). The number of variants is shown on a piecewise-linear axis, with horizontal positioning permuted to assist visualization. Where nose-colonizing and infecting bacteria possessed different multilocus sequence types, the number of variants between those populations is colored red. When the number of B-class variants was 66 or less, nose-colonizing and infecting bacteria were considered related, since a similar range of (C-class) diversity was observed within the nose-colonizing populations of bacteria with the same multilocus sequence type. When the number of B-class variants was 1104 or more, nose-colonizing and infecting bacteria were considered unrelated.