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

BACKGROUND: Mycobacterium 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. RESULTS: We 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. CONCLUSIONS: This 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 BACKGROUND: Mycobacterium 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. RESULTS: We 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. CONCLUSIONS: This 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 ATCC 19977 reference strain
29 DrugBank database
30 ES proteins
31 MAB ES proteins
32 MAB R variants
33 MAB genomes
34 MAB pathogenicity
35 MAB secretomes
36 MAB subspecies
37 MCE domains
38 MTBC
39 Mycobacterium abscessus
40 Mycobacterium abscessus complex
41 R variants
42 Secret-AAR
43 abscessus
44 abscessus ATCC 19977
45 abscessus ATCC 19977 reference strain
46 abscessus complex
47 abscessus subsp
48 abundance
49 antigenic density
50 antigenic differences
51 approach
52 bioinformatics pipeline
53 bioinformatics strategy
54 bolletii
55 candidate proteins
56 characterization
57 clinical isolates
58 colonization
59 colony morphotypes
60 comparison
61 complexes
62 database
63 density
64 diagnostic marker
65 differences
66 domain
67 drug targets
68 essential genes
69 essential proteins
70 essential role
71 experimental approach
72 experimental support
73 first systematic prediction
74 genes
75 genome
76 growth
77 high abundance
78 higher antigenic density
79 homologues
80 homology
81 host
82 importance
83 infection
84 insights
85 investigation
86 isolates
87 list
88 markers
89 morphotypes
90 mycobacteria
91 mycobacterial secretomes
92 new vaccines
93 non-ES proteins
94 non-tuberculous mycobacteria
95 pathogenic non-tuberculous mycobacterium
96 pathogenicity
97 pathway
98 pipeline
99 prediction
100 previous experimental support
101 protein
102 protein drug targets
103 reference strains
104 robust bioinformatics pipeline
105 role
106 rough colony morphotype
107 secretion
108 secretome
109 secretome characterization
110 silico characterization
111 smooth morphotype
112 strains
113 strategies
114 study
115 subsp
116 subspecies
117 support
118 survival
119 systematic investigation
120 systematic prediction
121 target
122 time-consuming experimental approaches
123 tuberculosis complex
124 tuberculosis secretomes
125 vaccine
126 variants
127 virulence
128 schema:name Secretome characterization of clinical isolates from the Mycobacterium abscessus complex provides insight into antigenic differences
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