FlaGs and webFlaGs: discovering novel biology through the analysis of gene neighbourhood conservation

Saha, Chayan Kumar; Pires, Rodrigo Sanches; Brolin, Harald; Delannoy, Maxence; Atkinson, Gemma C.

doi:10.1093/bioinformatics/btaa788

“…Protein accession numbers were subjected to flanking genes (FlaGs) analysis [50] to establish the conservation of T7b genes across multiple L. monocytogenes strains. Gene products were analysed using blastp analysis, and the presence of transmembrane regions was predicted using TMHMM [51].…”

Section: Methodsmentioning

confidence: 99%

Extreme genetic diversity in the type VII secretion system of Listeria monocytogenes suggests a role in bacterial antagonism

Bowran

¹

,

Palmer

²

2021

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The type VII protein secretion system (T7SS) has been characterized in members of the phyla Actinobacteria and Firmicutes. In mycobacteria the T7SS is intimately linked with pathogenesis and intracellular survival, while in Firmicutes there is mounting evidence that the system plays a key role in interbacterial competition. A conserved membrane-bound ATPase protein, termed EssC in Staphylococcus aureus , is a critical component of the T7SS and is the primary receptor for substrate proteins. Genetic diversity in the essC gene of S. aureus has previously been reported, resulting in four protein variants that are linked to specific subsets of substrates. Here we have analysed the genetic diversity of the T7SS-encoding genes and substrate proteins across Listeria monocytogenes genome sequences. We find that there are seven EssC variants across the species that differ in their C-terminal region; each variant is correlated with a distinct subset of genes for likely substrate and accessory proteins. EssC1 is most common and is exclusively linked with polymorphic toxins harbouring a YeeF domain, whereas EssC5, EssC6 and EssC7 variants all code for an LXG domain protein adjacent to essC. Some essC1 variant strains encode an additional, truncated essC at their T7 gene cluster. The truncated EssC, comprising only the C-terminal half of the protein, matches the sequence of either EssC2, EssC3 or EssC4. In each case the truncated gene directly precedes a cluster of substrate/accessory protein genes acquired from the corresponding strain. Across L. monocytogenes strains we identified 40 LXG domain proteins, most of which are encoded at conserved genomic loci. These loci also harbour genes encoding immunity proteins and sometimes additional toxin fragments. Collectively our findings strongly suggest that the T7SS plays an important role in bacterial antagonism in this species.

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“…To determine whether the system identified in S. marcescens DB10 could be regarded as a general secretion pathway, we undertook a search across bacterial genomes using the sequence of the S. marcescens ChiX L‐Ala D‐Glu endopeptidase, followed by the analysis of gene neighborhood conservation (Saha et al, 2020). As seen in Figure 3a and S1, the chiR ‐ chiB‐chiWXYZ organization is well conserved across Serratia species, as is the presence of maeB , encoding a predicted NADP‐dependent oxaloacetate‐decarboxylating malate dehydrogenase, downstream of chiZ .…”

Section: Introductionmentioning

confidence: 99%

“…Protein sequence accessions were retrieved from the NCBI RefSeq database ( https://www.ncbi.nlm.nih.gov/) through a BlastP search with S. marcescens ChiX as the query, limiting to the top 500 hits, and reducing redundancy by excluding most E. coli strains. These accessions were used as input for FlaGs.py, which retrieves the protein sequences encoded by flanking genes and clusters them into homologous families (Saha et al, 2020 and available on‐line at http://130.239.193.227/html/webFlaGs.html). In part A, manual searching identified chiZ genes overlapping with chiY in S. odorifera , S. ficaria, and S. marcescens which were not annotated in the available genome sequences and are not included on the figure.…”

Section: Introductionmentioning

confidence: 99%

“…Protein sequence accessions were retrieved from the NCBI RefSeq database ( https://www.ncbi.nlm.nih.gov/) through a BlastP search with S. marcescens ChiX as the query, limiting to the top 500 hits, and reducing redundancy by excluding most E. coli strains. These accessions were used as input for FlaGs.py (Saha et al, 2020 and http://130.239.193.227/html/webFlaGs.html). Holin genes identified were of the 3‐3 family (Reddy and Saier, 2013).…”

Section: Introductionmentioning

confidence: 99%

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A holin/peptidoglycan hydrolase‐dependent protein secretion system

Palmer

¹

,

Finney

²

,

Saha

³

et al. 2020

Molecular Microbiology

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“…In the new paper the authors look in detail at the repertoire of T7SS in the food poisoning bacterium Listeria monocytogenes, using a comparative genomic approach based on searching for the conserved membrane-bound ATPase component of the secretion system EssC. As well as using regular bioinformatics tools, Kieran used the new FlaGs tool [5] from Chayan Kumar Saha (@chayan_saha7) and Gemma Atkinson (@gem__atkinson) at Umea University, Sweden, which uses genome context to discover relationships between homologous genes in different genomes. Across L. monocytogenes genomes they identify seven different EssC variants, each of which they propose will direct their own particular set of protein substrates for secretion.…”

mentioning

confidence: 99%