Identifying Bacterial Menu Choices from the Host Buffet during Infections

Abstract

During his development of the germ theory of disease, Louis Pasteur compared cholera and anthrax infections and remarked “Quelle difference donc entre le vibrion septique et cette bacteridie, et n’est-il pas remarquable de voir se multiplier dans 1=organization animale des etres aussi dissemblables par leur mode de nutrition!” (1). An abridged English translation of this phrase reads “So what’s the difference between the septic vibrio and this (anthrax) bacillus, and is it not remarkable to see the organization of microscopic beings so dissimilar in their mode of nutrition multiply in the animal!” While Louis Pasteur made many seminal contributions to microbiology, one concept that has been largely overlooked is the role of pathogen nutrition and physiology during infection, specifically with regard to carbon nutrition (2). In this context, Jorth et al. (3) have explored the use of RNA sequencing (RNA-seq) and next-generation sequencing to obtain a high-resolution transcriptome of Aggregatibacter actinomycetemcomitans during growth in vitro and in a murine abscess infection. They identified a large number of metabolic genes whose expression is differentially upregulated during infection, including those for formate dehydrogenase (fdhF1F2) and fumarate reductase (frdA tofrdD), which are associated with fermentative and anaerobic metabolism, respectively. Mutants lacking these genes retained in vitro growth characteristics but experienced a 10-fold reduction in bacterial numbers in a mouse abscess, thus confirming the RNA-seq results. Previous studies of A. actinomycetemcomitans abscess formation by other investigators concentrated on virulence properties (4), so metabolic genes were not identified. Overall, the experimental strategy described by Jorth et al. (3) provides a nice template for future investigations of bacterial physiology during infectious processes.