A quantitative framework reveals traditional laboratory growth is a highly accurate model of human oral infection.

Bacterial behavior and virulence during human infection is difficult to study and largely unknown, as our vast knowledge of infection microbiology is primarily derived from studies using in vitro and animal models. Here, we characterize the physiology of , a periodontal pathogen, in its native environment using 93 published metatranscriptomic datasets from periodontally healthy and diseased individuals. transcripts were more abundant in samples from periodontally diseased patients but only above 0.1% relative abundance in one-third of diseased samples. During human infection, highly expressed genes encoding virulence factors such as fimbriae and gingipains (proteases) and genes involved in growth and metabolism, indicating that is actively growing during disease. A quantitative framework for assessing the accuracy of model systems showed that 96% of genes were expressed similarly in periodontitis and in vitro midlogarithmic growth, while significantly fewer genes were expressed similarly in periodontitis and in vitro stationary phase cultures (72%) or in a murine abscess infection model (85%). This high conservation in gene expression between periodontitis and logarithmic laboratory growth is driven by overall low variance in gene expression, relative to other pathogens including and Together, this study presents strong evidence for the use of simple test tube growth as the gold standard model for studying biology, providing biological relevance for the thousands of laboratory experiments performed with logarithmic phase Furthermore, this work highlights the need to quantitatively assess the accuracy of model systems.