期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：2
DOI：10.1073/pnas.2116637119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Most microbial knowledge comes from experiments in laboratory models, despite the assumption that these artificial systems alter microbial physiology relative the native environment. We tested this assumption for an oral pathogen,
Porphyromonas gingivalis, using 93 metatranscriptomes from periodontally healthy and diseased patients and 122 transcriptomes from experimental models. We discovered that a simple in vitro model, midlogarithmic growth in rich media, highly recapitulates
P. gingivalis gene expression in the human oral cavity, outperforming other models, including a murine infection model. These results support the biological relevance of decades of laboratory experiments with this pathogen and validate an accessible experimental model for studying
P. gingivalis biology. Furthermore, these data provide a conceptual framework for understanding in situ gene expression across microbes.
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
Porphyromonas gingivalis, a periodontal pathogen, in its native environment using 93 published metatranscriptomic datasets from periodontally healthy and diseased individuals.
P. gingivalis 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,
P. gingivalis highly expressed genes encoding virulence factors such as fimbriae and gingipains (proteases) and genes involved in growth and metabolism, indicating that
P. gingivalis is actively growing during disease. A quantitative framework for assessing the accuracy of model systems showed that 96% of
P. gingivalis 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
P. gingivalis gene expression, relative to other pathogens including
Pseudomonas aeruginosa and
Staphylococcus aureus. Together, this study presents strong evidence for the use of simple test tube growth as the gold standard model for studying
P. gingivalis biology, providing biological relevance for the thousands of laboratory experiments performed with logarithmic phase
P. gingivalis. Furthermore, this work highlights the need to quantitatively assess the accuracy of model systems.
