TY - JOUR T1 - A Tn-seq screen of <em>Streptococcus pneumoniae</em> uncovers DNA repair as the major pathway for desiccation tolerance and transmission JF - bioRxiv DO - 10.1101/2020.11.09.375980 SP - 2020.11.09.375980 AU - Allison J. Matthews AU - Hannah M. Rowe AU - Jason W. Rosch AU - Andrew Camilli Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/11/10/2020.11.09.375980.abstract N2 - Streptococcus pneumoniae is an opportunistic pathogen that is a common cause of serious invasive diseases such as pneumonia, bacteremia, meningitis, and otitis media. Transmission of this bacterium has classically been thought to occur through inhalation of respiratory droplets and direct contact with nasal secretions. However, the demonstration that S. pneumoniae is desiccation tolerant, and therefore environmentally stable for extended periods of time, opens up the possibility that this pathogen is also transmitted via contaminated surfaces (fomites). To better understand the molecular mechanisms that enable S. pneumoniae to survive periods of desiccation, we performed a high throughput transposon sequencing (Tn-seq) screen in search of genetic determinants of desiccation tolerance. We identified 42 genes whose disruption reduced desiccation tolerance, and 45 genes that enhanced desiccation tolerance. The nucleotide excision repair pathway was the most enriched category in our Tn-seq results, and we found that additional DNA repair pathways are required for desiccation tolerance, demonstrating the importance of maintaining genome integrity after desiccation. Deletion of the nucleotide excision repair gene uvrA resulted in decreased transmission efficiency between infant mice, indicating a correlation between desiccation tolerance and pneumococcal transmission. Understanding the molecular mechanisms that enable pneumococcal persistence in the environment may enable targeting of these pathways to prevent fomite transmission, thereby preventing the establishment of new colonization and any resulting invasive disease. ER -