1. Genome‐wide identification of Streptococcus sanguinis fitness genes in human serum and discovery of potential selective drug targets
- Author
-
Haider H. Nadhem, Bin Zhu, Ping Xu, Todd Kitten, Xiuchun Ge, Henry Ge, Tanya Puccio, Liang Bao, and Shannon P. Green
- Subjects
DNA, Bacterial ,Male ,Virulence Factors ,medicine.drug_class ,Antibiotics ,Virulence ,Microbiology ,Genome ,03 medical and health sciences ,Bacterial Proteins ,Streptococcal Infections ,medicine ,Animals ,Humans ,Endocarditis ,Saliva ,Molecular Biology ,Gene ,Research Articles ,030304 developmental biology ,0303 health sciences ,biology ,infective endocarditis ,030306 microbiology ,Membrane Transport Proteins ,purine metabolism ,sequencing ,Endocarditis, Bacterial ,medicine.disease ,biology.organism_classification ,Specific Pathogen-Free Organisms ,Streptococcus sanguinis ,Blood ,Purines ,Infective endocarditis ,Mutation ,ATP-Binding Cassette Transporters ,Genetic Fitness ,Rabbits ,Oral Microbiome ,Streptococcus sanguis ,Metabolic Networks and Pathways ,Research Article ,Genome-Wide Association Study - Abstract
Streptococcus sanguinis is a primary colonizer of teeth and is associated with oral health. When it enters the bloodstream, however, this bacterium may cause the serious illness infective endocarditis. The genes required for survival and proliferation in blood have not been identified. The products of these genes could provide a rich source of targets for endocarditis‐specific antibiotics possessing greater efficacy for endocarditis, and also little or no activity against those bacteria that remain in the mouth. We previously created a comprehensive library of S. sanguinis mutants lacking every nonessential gene. We have now screened each member of this library for growth in human serum and discovered 178 mutants with significant abundance changes. The main biological functions disrupted in these mutants, including purine metabolism, were highlighted via network analysis. The components of an ECF‐family transporter were required for growth in serum and were shown for the first time in any bacterium to be essential for endocarditis virulence. We also identified two mutants whose growth was reduced in serum but not in saliva. This strategy promises to enable selective targeting of bacteria based on their location in the body, in this instance, treating or preventing endocarditis while leaving the oral microbiome intact., The fitness of S. sanguinis mutants in human serum was screened by ORF‐seq. The biological functions of these fitness genes were analyzed. The virulence factors in a rabbit endocarditis model and potential selective drug targets in human serum were explored.
- Published
- 2020