English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Mycobacterium abscessus  ( Mab ) is a rapidly growing non-tuberculous mycobacterium (NTM) that causes a wide range of infections. Treatment of  Mab  infections is difficult because the bacterium is intrinsically resistant to many classes of antibiotics. Developing new and effective treatments against  Mab  requires a better understanding of the unique vulnerabilities that can be targeted for future drug development. To achieve this, we identified essential genes in  Mab  by conducting transposon sequencing (TnSeq) on the reference  Mab  strain ATCC 19977. We generated ~51,000 unique transposon mutants and used this high-density library to identify 362 essential genes for in vitro growth. To investigate species-specific vulnerabilities in  Mab , we further characterized  MAB_3167c , a predicted penicillin-binding protein and hypothetical lipoprotein (PBP-lipo) that is essential in  Mab  and non-essential in  Mycobacterium tuberculosis  ( Mtb ). We found that PBP-lipo primarily localizes to the subpolar region and later to the septum as cells prepare to divide. Depletion of  Mab  PBP-lipo causes cells to elongate, develop ectopic branches, and form multiple septa. Knockdown of PBP-lipo along with PbpB, DacB1, and a carboxypeptidase, MAB_0519 lead to synergistic growth arrest. In contrast, these genetic interactions were absent in the  Mtb  model organism,  Mycobacterium smegmatis , indicating that the PBP-lipo homologs in the two species exist in distinct genetic networks. Finally, repressing PBP-lipo sensitized the reference strain and 11  Mab  clinical isolates to several classes of antibiotics, including the β-lactams, ampicillin, and amoxicillin by greater than 128-fold. Altogether, this study presents PBP-lipo as a key enzyme to study  Mab -specific processes in cell wall synthesis and importantly positions PBP-lipo as an attractive drug target to treat  Mab  infections.

elife

Transposon mutagenesis in  Mycobacterium abscessus  identifies an essential penicillin-binding protein involved in septal peptidoglycan synthesis and antibiotic sensitivity