Predominantly Orphan Secretome in the Lung Pathogen Mycobacterium abscessus Revealed by a Multipronged Growth-Phase-Driven Strategy.
Microorganisms
; 12(2)2024 Feb 12.
Article
em En
| MEDLINE
| ID: mdl-38399782
ABSTRACT
The emerging lung pathogen Mycobacterium abscessus is understudied for its virulence determinants and molecular targets for diagnosis and therapeutics. Here, we report a comprehensive secretome (600 proteins) of this species, which was identified using a multipronged strategy based on genetic/genomic, proteomic, and bioinformatic approaches. In-solution digested bottom-up proteomics from various growth phases identified a total of 517 proteins, while 2D-GE proteomics identified 33 proteins. A reporter-gene-fusion-based genomic library that was custom-generated in this study enabled the detection of 23 secretory proteins. A genome-wide survey for N-terminal signal sequences using bioinformatic tools (Psortb 2.0 and SignalP 3.0) combined with a strategy of the subtraction of lipoproteins and proteins containing multiple transmembrane domains yielded 116 secretory proteins. A homology search against the M. tuberculosis database identified nine additional secretory protein homologs that lacked a secretory signal sequence. Considering the little overlap (80 proteins) among the different approaches used, this study emphasized the importance of using a multipronged strategy for a comprehensive understanding of the secretome. Notably, the majority of the secreted proteins identified (over 50%) turned out to be "orphans" (those with no known functional homologs). The revelation of these species-specific orphan proteins offers a hitherto unexplored repertoire of potential targets for diagnostic, therapeutic, and vaccine research in this emerging lung pathogen.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Microorganisms
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos