Secretome characterization of clinical isolates from the Mycobacterium abscessus complex provides insight into antigenic differences View Full Text


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Article Info

DATE

2021-05-25

AUTHORS

Fernanda Cornejo-Granados, Thomas A. Kohl, Flor Vásquez Sotomayor, Sönke Andres, Rogelio Hernández-Pando, Juan Manuel Hurtado-Ramirez, Christian Utpatel, Stefan Niemann, Florian P. Maurer, Adrian Ochoa-Leyva

ABSTRACT

BackgroundMycobacterium abscessus (MAB) is a widely disseminated pathogenic non-tuberculous mycobacterium (NTM). Like with the M. tuberculosis complex (MTBC), excreted / secreted (ES) proteins play an essential role for its virulence and survival inside the host. Here, we used a robust bioinformatics pipeline to predict the secretome of the M. abscessus ATCC 19977 reference strain and 15 clinical isolates belonging to all three MAB subspecies, M. abscessus subsp. abscessus, M. abscessus subsp. bolletii, and M. abscessus subsp. massiliense.ResultsWe found that ~ 18% of the proteins encoded in the MAB genomes were predicted as secreted and that the three MAB subspecies shared > 85% of the predicted secretomes. MAB isolates with a rough (R) colony morphotype showed larger predicted secretomes than isolates with a smooth (S) morphotype. Additionally, proteins exclusive to the secretomes of MAB R variants had higher antigenic densities than those exclusive to S variants, independent of the subspecies. For all investigated isolates, ES proteins had a significantly higher antigenic density than non-ES proteins. We identified 337 MAB ES proteins with homologues in previously investigated M. tuberculosis secretomes. Among these, 222 have previous experimental support of secretion, and some proteins showed homology with protein drug targets reported in the DrugBank database. The predicted MAB secretomes showed a higher abundance of proteins related to quorum-sensing and Mce domains as compared to MTBC indicating the importance of these pathways for MAB pathogenicity and virulence. Comparison of the predicted secretome of M. abscessus ATCC 19977 with the list of essential genes revealed that 99 secreted proteins corresponded to essential proteins required for in vitro growth.ConclusionsThis study represents the first systematic prediction and in silico characterization of the MAB secretome. Our study demonstrates that bioinformatics strategies can help to broadly explore mycobacterial secretomes including those of clinical isolates and to tailor subsequent, complex and time-consuming experimental approaches accordingly. This approach can support systematic investigation exploring candidate proteins for new vaccines and diagnostic markers to distinguish between colonization and infection. All predicted secretomes were deposited in the Secret-AAR web-server (http://microbiomics.ibt.unam.mx/tools/aar/index.php). More... »

PAGES

385

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12864-021-07670-7

DOI

http://dx.doi.org/10.1186/s12864-021-07670-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1138341546

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/34034663


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20 schema:description BackgroundMycobacterium abscessus (MAB) is a widely disseminated pathogenic non-tuberculous mycobacterium (NTM). Like with the M. tuberculosis complex (MTBC), excreted / secreted (ES) proteins play an essential role for its virulence and survival inside the host. Here, we used a robust bioinformatics pipeline to predict the secretome of the M. abscessus ATCC 19977 reference strain and 15 clinical isolates belonging to all three MAB subspecies, M. abscessus subsp. abscessus, M. abscessus subsp. bolletii, and M. abscessus subsp. massiliense.ResultsWe found that ~ 18% of the proteins encoded in the MAB genomes were predicted as secreted and that the three MAB subspecies shared > 85% of the predicted secretomes. MAB isolates with a rough (R) colony morphotype showed larger predicted secretomes than isolates with a smooth (S) morphotype. Additionally, proteins exclusive to the secretomes of MAB R variants had higher antigenic densities than those exclusive to S variants, independent of the subspecies. For all investigated isolates, ES proteins had a significantly higher antigenic density than non-ES proteins. We identified 337 MAB ES proteins with homologues in previously investigated M. tuberculosis secretomes. Among these, 222 have previous experimental support of secretion, and some proteins showed homology with protein drug targets reported in the DrugBank database. The predicted MAB secretomes showed a higher abundance of proteins related to quorum-sensing and Mce domains as compared to MTBC indicating the importance of these pathways for MAB pathogenicity and virulence. Comparison of the predicted secretome of M. abscessus ATCC 19977 with the list of essential genes revealed that 99 secreted proteins corresponded to essential proteins required for in vitro growth.ConclusionsThis study represents the first systematic prediction and in silico characterization of the MAB secretome. Our study demonstrates that bioinformatics strategies can help to broadly explore mycobacterial secretomes including those of clinical isolates and to tailor subsequent, complex and time-consuming experimental approaches accordingly. This approach can support systematic investigation exploring candidate proteins for new vaccines and diagnostic markers to distinguish between colonization and infection. All predicted secretomes were deposited in the Secret-AAR web-server (http://microbiomics.ibt.unam.mx/tools/aar/index.php).
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27 schema:keywords ATCC 19977
28 ConclusionsThis study
29 DrugBank database
30 ES proteins
31 M. abscessus ATCC 19977
32 M. abscessus subsp
33 M. tuberculosis complex
34 MCE domains
35 Mycobacterium abscessus complex
36 R variants
37 ResultsWe
38 S variants
39 abscessus
40 abundance
41 antigenic density
42 antigenic differences
43 approach
44 bioinformatics pipeline
45 bioinformatics strategy
46 bolletii
47 candidate proteins
48 characterization
49 clinical isolates
50 colonization
51 colony morphotypes
52 comparison
53 complexes
54 database
55 density
56 diagnostic marker
57 differences
58 domain
59 drug targets
60 essential genes
61 essential proteins
62 essential role
63 experimental approach
64 experimental support
65 genes
66 genome
67 growth
68 high abundance
69 higher antigenic density
70 homologues
71 homology
72 host
73 importance
74 infection
75 insights
76 investigation
77 isolates
78 list
79 mAbs
80 markers
81 morphotypes
82 mycobacteria
83 new vaccines
84 non-ES proteins
85 non-tuberculous mycobacteria
86 pathogenic non-tuberculous mycobacterium
87 pathogenicity
88 pathway
89 pipeline
90 prediction
91 protein
92 protein drug targets
93 reference strains
94 robust bioinformatics pipeline
95 role
96 rough colony morphotype
97 secretion
98 secretome
99 secretome characterization
100 silico characterization
101 smooth morphotype
102 strains
103 strategies
104 study
105 subsp
106 subspecies
107 support
108 survival
109 systematic investigation
110 systematic prediction
111 target
112 time-consuming experimental approaches
113 tuberculosis complex
114 vaccine
115 variants
116 virulence
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