Enhanced biofilm and extracellular matrix production by chronic carriage versus acute isolates of Salmonella Typhi

• Published in: PLoS pathogens 2021-01, Vol.17 (1), p.e1009209-e1009209
• Main Authors: Devaraj, Aishwarya, González, Juan F, Eichar, Bradley, Thilliez, Gatan, Kingsley, Robert A, Baker, Stephen, Allard, Marc W, Bakaletz, Lauren O, Gunn, John S, Goodman, Steven D
• Format: Article
• Language: English
• Subjects: Antibiotics; Antibodies, Monoclonal - pharmacology; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bile; Biofilms; Biofilms - drug effects; Biofilms - growth & development; Biology and Life Sciences; Biomass; Calculi; Cellular proteins; Chronic infection; Computer and Information Sciences; DnaB Helicases - antagonists & inhibitors; DnaB Helicases - genetics; DnaB Helicases - metabolism; Environmental DNA; Extracellular matrix; Extracellular Matrix - metabolism; Gallbladder; Gallstones; Gene expression; Genetic aspects; Genomes; Health aspects; Humans; Infections; Integration Host Factors - genetics; Integration Host Factors - metabolism; Medicine and Health Sciences; Microbial mats; Mortality; Phylogenetics; Phylogeny; Proteins; Salmonella; Salmonella typhi - classification; Salmonella typhi - genetics; Salmonella typhi - pathogenicity; Salmonella typhosa; Stationary phase; Typhoid; Typhoid Fever - drug therapy; Typhoid Fever - immunology; Typhoid Fever - microbiology
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1009209

Salmonella Typhi is the primary causative agent of typhoid fever; an acute systemic infection that leads to chronic carriage in 3-5% of individuals. Chronic carriers are asymptomatic, difficult to treat and serve as reservoirs for typhoid outbreaks. Understanding the factors that contribute to chronic carriage is key to development of novel therapies to effectively resolve typhoid fever. Herein, although we observed no distinct clustering of chronic carriage isolates via phylogenetic analysis, we demonstrated that chronic isolates were phenotypically distinct from acute infection isolates. Chronic carriage isolates formed significantly thicker biofilms with greater biomass that correlated with significantly higher relative levels of extracellular DNA (eDNA) and DNABII proteins than biofilms formed by acute infection isolates. Importantly, extracellular DNABII proteins include integration host factor (IHF) and histone-like protein (HU) that are critical to the structural integrity of bacterial biofilms. In this study, we demonstrated that the biofilm formed by a chronic carriage isolate in vitro, was susceptible to disruption by a specific antibody against DNABII proteins, a successful first step in the development of a therapeutic to resolve chronic carriage.