Therapeutically useful mycobacteriophages BPs and Muddy require trehalose polyphleates.

Nat Microbiol

Centre National de la Recherche Scientifique UMR 9004, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier, Montpellier, France.

Published: September 2023

AI Article Synopsis

  • Mycobacteriophages like BPs and Muddy show potential as treatments for non-tuberculous mycobacterial infections, particularly Mycobacterium abscessus and Mycobacterium smegmatis.
  • The study identifies trehalose polyphleates (TPPs) as crucial for phage infection, where their absence leads to decreased phage adsorption and increased resistance due to primary mutations.
  • Phage resistance can arise from TPP loss, but some phages can adapt to become TPP-independent, suggesting that using these adapted phages in clinical settings may reduce resistance issues.

Article Abstract

Mycobacteriophages show promise as therapeutic agents for non-tuberculous mycobacterium infections. However, little is known about phage recognition of Mycobacterium cell surfaces or mechanisms of phage resistance. We show here that trehalose polyphleates (TPPs)-high-molecular-weight, surface-exposed glycolipids found in some mycobacterial species-are required for infection of Mycobacterium abscessus and Mycobacterium smegmatis by clinically useful phages BPs and Muddy. TPP loss leads to defects in adsorption and infection and confers resistance. Transposon mutagenesis shows that TPP disruption is the primary mechanism for phage resistance. Spontaneous phage resistance occurs through TPP loss by mutation, and some M. abscessus clinical isolates are naturally phage-insensitive due to TPP synthesis gene mutations. Both BPs and Muddy become TPP-independent through single amino acid substitutions in their tail spike proteins, and M. abscessus mutants resistant to TPP-independent phages reveal additional resistance mechanisms. Clinical use of BPs and Muddy TPP-independent mutants should preempt phage resistance caused by TPP loss.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10465359PMC
http://dx.doi.org/10.1038/s41564-023-01451-6DOI Listing

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Similar Publications

Therapeutically useful mycobacteriophages BPs and Muddy require trehalose polyphleates.

Nat Microbiol

September 2023

Centre National de la Recherche Scientifique UMR 9004, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier, Montpellier, France.

Article Synopsis
  • Mycobacteriophages like BPs and Muddy show potential as treatments for non-tuberculous mycobacterial infections, particularly Mycobacterium abscessus and Mycobacterium smegmatis.
  • The study identifies trehalose polyphleates (TPPs) as crucial for phage infection, where their absence leads to decreased phage adsorption and increased resistance due to primary mutations.
  • Phage resistance can arise from TPP loss, but some phages can adapt to become TPP-independent, suggesting that using these adapted phages in clinical settings may reduce resistance issues.
View Article and Find Full Text PDF
Article Synopsis
  • Mycobacteriophages, which are viruses that infect bacteria, are valuable for studying their bacterial hosts and may be effective treatments for certain bacterial infections.
  • The study found that surface structures called trehalose polyphleates (TPPs) are essential for the infection process, and losing these structures makes bacteria resistant to phage attacks.
  • Mutations enabling phages BPs and Muddy to infect without TPPs suggest that TPP loss can lead to resistance, signaling that using modified phages might help avoid this issue in clinical settings.
View Article and Find Full Text PDF

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