Bacterial Factors Required for Transmission of Streptococcus pneumoniae in Mammalian Hosts

• Published in: Cell host & microbe 2019-06, Vol.25 (6), p.884-891.e6
• Main Authors: Rowe, Hannah M., Karlsson, Erik, Echlin, Haley, Chang, Ti-Cheng, Wang, Lei, van Opijnen, Tim, Pounds, Stanley B., Schultz-Cherry, Stacey, Rosch, Jason W.
• Format: Article
• Language: English
• Subjects: Animals; Disease Models, Animal; ferret; Ferrets; Genetic Testing; High-Throughput Screening Assays; Infectious Disease Transmission, Vertical - prevention & control; influenza; Mice; Mutagenesis, Insertional; Pneumococcal Infections - microbiology; Pneumococcal Infections - prevention & control; Pneumococcal Infections - transmission; Pneumococcal Vaccines - administration & dosage; Pneumococcal Vaccines - immunology; Pneumococcal Vaccines - isolation & purification; Sequence Analysis, DNA; Streptococcus pneumoniae; Streptococcus pneumoniae - genetics; Streptococcus pneumoniae - isolation & purification; transmission; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - immunology; Vaccines, Synthetic - isolation & purification; Virulence Factors - genetics; Virulence Factors - immunology
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2019.04.012

The capacity of Streptococcus pneumoniae to successfully transmit and colonize new human hosts is a critical aspect of pneumococcal population biology and a prerequisite for invasive disease. However, the bacterial mechanisms underlying this process remain largely unknown. To identify bacterial factors required for transmission, we conducted a high-throughput genetic screen with a transposon sequencing (Tn-seq) library of a pneumococcal strain in a ferret transmission model. Key players in both metabolism and transcriptional regulation were identified as required for efficient bacterial transmission. Targeted deletion of the putative C3-degrading protease CppA, iron transporter PiaA, or competence regulatory histidine kinase ComD significantly decreased transmissibility in a mouse model, further validating the screen. Maternal vaccination with recombinant surface-exposed PiaA and CppA alone or in combination blocked transmission in offspring and were more effective than capsule-based vaccines. These data underscore the possibility of targeting pneumococcal transmission as a means of eliminating invasive disease in the population. [Display omitted] •A pneumococcal Tn-seq library was screened in a ferret transmission model•The fitness landscape of S. pneumoniae genes during mammalian transmission established•Metabolic factors enhance pneumococcal environmental stability•Vaccinating dams with identified factors blocks pneumococcal transmission in offspring Rowe et al. conduct a screen to identify pneumococcal genes required for effective transmission in a ferret model. They establish the fitness landscape of S. pneumoniae genes during mammalian transmission and find that maternal vaccination with the identified transmission factors can block bacterial transmission in the offspring.