Severe infections emerge from commensal bacteria by adaptive evolution

Area of Science:

• Microbiology
• Genomics
• Evolutionary Biology

Background:

• Bacteria causing significant global mortality often colonize humans without causing severe infections.
• The relationship between mutation, selection in commensal bacteria, and subsequent infection is not well understood.

Purpose of the Study:

• To investigate de novo mutations and adaptive evolution in Staphylococcus aureus during infection.
• To determine if within-host selection pressures differentiate infecting from colonizing bacteria.

Main Methods:

• Whole-genome sequencing of 1163 Staphylococcus aureus isolates from 105 infected patients with concurrent nasal colonization.
• Comparative genomic analysis to identify de novo mutations and adaptive signatures in infecting versus colonizing strains.
• Analysis of gene enrichment in response to virulence regulators (rsp, agr) and antimicrobial peptides.

Main Results:

• Infections predominantly (72%) originated from nasal colonization.
• Significant adaptive enrichment (2.8-3.6 fold) of protein-altering variants in genes regulated by rsp and agr, and in response to antimicrobial peptides.
• Adaptive mutations in pathogenesis-associated genes were 3.1-fold enriched in infecting bacteria but absent in colonizing bacteria and healthy carriers.
• These signatures indicate short-term, within-host selection pressures specific to infection.

Conclusions:

• Spontaneous adaptive evolution signatures are specifically associated with Staphylococcus aureus infection, not mere colonization.
• Within-host evolution and selection pressures play a critical role in the transition from colonization to infection.
• Findings suggest potential for novel diagnostic and therapeutic targets based on infection-associated adaptive mutations.