Bap-Independent Biofilm Formation in Staphylococcus xylosus

The biofilm associated protein (Bap) is recognised as the essential component for biofilm formation in Staphylococcus aureus V329 and has been predicted as important for other species as well. Although Bap orthologs are also present in most S. xylosus strains, their contribution to biofilm formation has not yet been demonstrated. In this study, different experimental approaches were used to elucidate the effect of Bap on biofilm formation in S. xylosus and the motif structure of two biofilm-forming S. xylosus strains TMW 2.1023 and TMW 2.1523 was compared to Bap of S. aureus V329. We found that despite an identical structural arrangement into four regions, Bap from S. xylosus differs in key factors to Bap of S. aureus, i.e., isoelectric point of aggregation prone Region B, protein homology and type of repeats. Disruption of bap had no effect on aggregation behavior of selected S. xylosus strains and biofilm formation was unaffected (TMW 2.1023) or at best slightly reduced under neutral conditions (TMW 2.1523). Further, we could not observe any typical characteristics of a S. aureus Bap-positive phenotype such as functional impairment by calcium addition and rough colony morphology on congo red agar (CRA). A dominating role of Bap in cell aggregation and biofilm formation as reported mainly for S. aureus V329 was not observed. In contrast, this work demonstrates that functions of S. aureus Bap cannot easily be extrapolated to S. xylosus Bap, which appears as non-essential for biofilm formation in this species. We therefore suggest that biofilm formation in S. xylosus follows different and multifactorial mechanisms.

Recent Advances in Protein Homology Detection Propelled by Inter-Residue Interaction Map Threading

Sequence-based protein homology detection has emerged as one of the most sensitive and accurate approaches to protein structure prediction. Despite the success, homology detection remains very challenging for weakly homologous proteins with divergent evolutionary profile. Very recently, deep neural network architectures have shown promising progress in mining the coevolutionary signal encoded in multiple sequence alignments, leading to reasonably accurate estimation of inter-residue interaction maps, which serve as a rich source of additional information for improved homology detection. Here, we summarize the latest developments in protein homology detection driven by inter-residue interaction map threading. We highlight the emerging trends in distant-homology protein threading through the alignment of predicted interaction maps at various granularities ranging from binary contact maps to finer-grained distance and orientation maps as well as their combination. We also discuss some of the current limitations and possible future avenues to further enhance the sensitivity of protein homology detection.

Improved DNA-versus-Protein Homology Search for Protein Fossils

Protein fossils, i.e. noncoding DNA descended from coding DNA, arise frequently from transposable elements (TEs), decayed genes, and viral integrations. They can reveal, and mislead about, evolutionary history and relationships. They have been detected by comparing DNA to protein sequences, but current methods are not optimized for this task. We describe a powerful DNA-protein homology search method. We use a 64×21 substitution matrix, which is fitted to sequence data, automatically learning the genetic code. We detect subtly homologous regions by considering alternative possible alignments between them, and calculate significance (probability of occurring by chance between random sequences). Our method detects TE protein fossils much more sensitively than blastx, and > 10× faster. Of the ~7 major categories of eukaryotic TE, three have not been found in mammals: we find two of them in the human genome, polinton and DIRS/Ngaro. This method increases our power to find ancient fossils, and perhaps to detect non-standard genetic codes. The alternative-alignments and significance paradigm is not specific to DNA-protein comparison, and could benefit homology search generally.

SARS-CoV-2 whole-genome classification analysis, protein homology modelling and elucidation of associated protein functions

The most recent whole-genome sequence of SARS-CoV-2 was published on NCBI on 13th March 2020, with accession no. NC_045512. The protein products, genetic features, sequence length, NCBI reference sequence, protein structures (published/ homology modelling) and functions are discussed and analysed in this paper. Multiple sequence alignment is performed and Phylogenic tree is prepared for the 4 closely related coronavirus species. This study provides the whole genome analysis with protein homology structures and elucidates functions of structurally similar proteins for further exploration and contributes to the search for anti-SARS-CoV-2 drugs. The application of this data in new vaccine development techniques such as Rapid-Response Platform and a possibility of a recombinant SARS-CoV-2 are discussed in this paper.