Mycobacterium abscessus est une bactérie non tuberculeuse, environnementale, à croissance rapide, qui est responsable d’infections pulmonaires sévères, notamment chez les patients atteints de mucoviscidose. Le traitement actuel combine l’utilisation d’une b-lactamine et d’un aminoglycoside associés à un macrolide. Cette bactérie est polyrésistante à la plupart des antibiotiques utilisés en clinique. Les mécanismes de résistance, innés ou acquis, qu’elle a développés, conduisent fréquemment à des échecs thérapeutiques, ce qui limite considérablement les moyens de lutte disponibles pour le clinicien. Une compréhension globale des mécanismes de résistance de cette bactérie s’avère ainsi nécessaire pour contrer les infections pulmonaires qu’elle provoque.
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 of Mycobacterium cell surfaces, or what molecules act as phage receptors. We show here that surface-exposed trehalose polyphleates (TPPs) are required for infection of Mycobacterium abscessus and Mycobacterium smegmatis by 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. Some M. abscessus clinical 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.
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