Mycobacteriumtrehalose polyphleates are required for mycobacteriophage infection

Autor: Katherine S. Wetzel, Morgane Illouz, Lawrence Abad, Haley G. Aull, Daniel A. Russell, Rebecca A. Garlena, Madison Cristinziano, Silke Malmsheimer, Christian Chalut, Graham F. Hatfull, Laurent Kremer
Rok vydání: 2023
Předmět:
Zdroj: bioRxiv
DOI: 10.1101/2023.03.14.532567
Popis: Mycobacteriophages are good model systems for understanding their bacterial hosts and show promise as therapeutic agents for nontuberculous mycobacterium infections. However, little is known about phage recognition ofMycobacteriumcell surfaces, or what molecules act as phage receptors. We show here that surface-exposed trehalose polyphleates (TPPs) are required for infection ofMycobacterium abscessusandMycobacterium smegmatisby clinically useful phages BPs and Muddy, and that TPP loss leads to defects in adsorption, infection, and confers resistance. Transposon mutagenesis indicates that TPP loss is the sole mechanism for phage resistance. However, both phages can overcome TPP loss through single amino acid substitutions in their tail spike proteins, suggesting that TPPs act to facilitate receptor recognition. SomeM. abscessusclinical isolates have defects in TPP synthesis but the phage tail spike mutants could effectively substitute for their parent phages in clinical use to circumvent resistance due to TPP loss.
Databáze: OpenAIRE