Bacterial hydrophilins promote pathogen desiccation tolerance

Acinetobacter baumannii is a leading cause of hospital-acquired infections, where outbreaks are driven by its ability to persist on surfaces in a desiccated state. Here, we show that A. baumannii causes more virulent pneumonia following desiccation and profile the genetic requirements for desiccation. We find that desiccation tolerance is enhanced upon the disruption of Lon protease, which targets unfolded and aggregated proteins for degradation. Notably, two bacterial hydrophilins, DtpA and DtpB, are transcriptionally upregulated in Δ lon via the two-component regulator, BfmR. These proteins, both hydrophilic and intrinsically disordered, promote desiccation tolerance in A. baumannii . Additionally, recombinant DtpA protects purified enzymes from inactivation and improves the desiccation tolerance of a probiotic bacterium when heterologously expressed. These results demonstrate a connection between environmental persistence and pathogenicity in A. baumannii , provide insight into the mechanisms of extreme desiccation tolerance, and reveal potential applications for bacterial hydrophilins in the preservation of protein- and live bacteria-based pharmaceuticals. • A. baumannii displays increased ability to colonize tissues following desiccation • A Tn-seq screen reveals that mutations in Lon protease increase desiccation tolerance • The predicted IDPs DtpA and DtpB are upregulated in Δ lon • Recombinant DtpA protects proteins from desiccation and heat inactivation Hospital surfaces are a major reservoir for the transmission of Acinetobacter baumannii . Green et al. determine that the virulence of A. baumannii is enhanced following drying and discover that desiccation tolerance is influenced by Lon protease through the modulation of the predicted intrinsically disordered hydrophilin proteins DtpA and DtpB.