Comparative Genomic Data Research Articles

ScRAPdb: an integrated pan-omics database for the Saccharomyces cerevisiae reference assembly panel.

As a unicellular eukaryote, the budding yeast Saccharomyces cerevisiae strikes a unique balance between biological complexity and experimental tractability, serving as a long-standing classic model for both basic and applied studies. Recently, S. cerevisiae further emerged as a leading system for studying natural diversity of genome evolution and its associated functional implication at population scales. Having high-quality comparative and functional genomics data are critical for such efforts. Here, we exhaustively expanded the telomere-to-telomere (T2T) S. cerevisiae reference assembly panel (ScRAP) that we previously constructed for 142 strains to cover high-quality genome assemblies and annotations of 264 S. cerevisiae strains from diverse geographical and ecological niches and also 33 outgroup strains from all the other Saccharomyces species complex. We created a dedicated online database, ScRAPdb (https://www.evomicslab.org/db/ScRAPdb/), to host this expanded pangenome collection. Furthermore, ScRAPdb also integrates an array of population-scale pan-omics atlases (pantranscriptome, panproteome and panphenome) and extensive data exploration toolkits for intuitive genomics analyses. All curated data and downstream analysis results can be easily downloaded from ScRAPdb. We expect ScRAPdb to become a highly valuable platform for the yeast community and beyond, leading to a pan-omics understanding of the global genetic and phenotypic diversity.

Signature of viral fossils: a comparative genomics approach to understand the diversity of endogenous retroviruses in bats

Endogenous retroviruses (ERVs) are traces of past viral infections commonly found in vertebrate genomes. Many ERVs are tightly regulated by the host genomes and co-opted for various functions within the hosts. Bats are the only true volant mammals, with the smallest mammalian genomes and a high fraction of ERVs within the genomes. They are important hosts for various zoonotic viral pathogens and can effectively modulate their immune response to tolerate viral infections. Integrations of retroviruses have been implicated as one of the mechanisms by which bats have co-evolved strategies to combat viral infections. In this study, we investigated the diversity of ERVs in over 40 publicly available bat genomes to understand the distribution and the evolution of ERVs within bats. We observed all classes of ERVs within bat genomes including even the complex lenti retroviruses. Alpha and spuma retroviruses which are, generally considered rare in mammals, were common within bats. We observed a positive correlation between bat genome size and length of ERV elements. Interestingly, nearly 30% of the ERVs within bats are intact suggesting a recent origin or co-option by the host genome. Future studies focusing on comparative genomic and experimental data will be critical to understand the role of these ERVs in host genome evolution.

Frontotemporal lobar degeneration targets brain regions linked to expression of recently evolved genes.

In frontotemporal lobar degeneration (FTLD), pathological protein aggregation in specific brain regions is associated with declines in human-specialized social-emotional and language functions. In most patients, disease protein aggregates contain either TDP-43 (FTLD-TDP) or tau (FTLD-tau). Here, we explored whether FTLD-associated regional degeneration patterns relate to regional gene expression of human accelerated regions (HARs), conserved sequences that have undergone positive selection during recent human evolution. To this end, we used structural neuroimaging from patients with FTLD and human brain regional transcriptomic data from controls to identify genes expressed in FTLD-targeted brain regions. We then integrated primate comparative genomic data to test our hypothesis that FTLD targets brain regions linked to expression levels of recently evolved genes. In addition, we asked whether genes whose expression correlates with FTLD atrophy are enriched for genes that undergo cryptic splicing when TDP-43 function is impaired. We found that FTLD-TDP and FTLD-tau subtypes target brain regions with overlapping and distinct gene expression correlates, highlighting many genes linked to neuromodulatory functions. FTLD atrophy-correlated genes were strongly enriched for HARs. Atrophy-correlated genes in FTLD-TDP showed greater overlap with TDP-43 cryptic splicing genes and genes with more numerous TDP-43 binding sites compared with atrophy-correlated genes in FTLD-tau. Cryptic splicing genes were enriched for HAR genes, and vice versa, but this effect was due to the confounding influence of gene length. Analyses performed at the individual-patient level revealed that the expression of HAR genes and cryptically spliced genes within putative regions of disease onset differed across FTLD-TDP subtypes. Overall, our findings suggest that FTLD targets brain regions that have undergone recent evolutionary specialization and provide intriguing potential leads regarding the transcriptomic basis for selective vulnerability in distinct FTLD molecular-anatomical subtypes.

Neuroendocrine cervical cancer: Have we made any steps forward in its management?

IntroductionNeuroendocrine tumors (NEC) were first described by Albores-Saavedra in 1972 and these tumors account for only 0.9% to 1.5% of all invasive cervical cancers.1,2 The most common type is small cell neuroendocrine carcinoma (SCNEC) of the cervix, which accounts for 80% of cases.2 The poor prognosis despite advances in treatment remains still a huge problem, so the aim of our review is to cover all current therapeutic options. MethodWe searched for all available interventional studies, reviews, case reports and meta-analyses published from 1995 to 2023. ResultsIn 2017 Castle et al.9 published a systematic review and meta-analysis and concluded that SCNC and large cell neuroendocrine carcinoma (LCNC) are, in most cases, caused by HPV, primarily HPV18 and HPV16. Comparative genomics data suggest that cervical NEC may be genetically more similar to common cervical cancer subtypes than to extra-cervical SCNEC of the lung and bladder.13 Surgery is recommended as the primary treatment in early stages of disease, with radical hysterectomy and nodal assessment followed by adjuvant pelvic radiotherapy and/or chemotherapy. However, simple hysterectomy may be adequate when followed by adjuvant radiotherapy with concurrent cisplatin and etoposide as additional chemotherapy.15 Considering that pathologic and clinical behavior is similar to small cell lung cancer, patients usually receive platinum and etoposide as part of their primary therapy.16 The recurrent disease remains a major clinical problem, because there is no standard treatment modality for these patients, and individualized therapy is recommeded. ConclusionCurrent therapeutic modalities are mainly based on experience in the treatment of SCNEC of the lung. Certainly, a multidisciplinary approach is very important inorder to design a personalized management plan.

Changing selection on amino acid substitutions in Gag protein between major HIV-1 subtypes.

Amino acid preferences at a protein site depend on the role of this site in protein function and structure as well as on external constraints. All these factors can change in the course of evolution, making amino acid propensities of a site time-dependent. When viral subtypes divergently evolve in different host subpopulations, such changes may depend on genetic, medical, and sociocultural differences between these subpopulations. Here, using our previously developed phylogenetic approach, we describe sixty-nine amino acid sites of the Gag protein of human immunodeficiency virus type 1 (HIV-1) where amino acids have different impact on viral fitness in six major subtypes of the type M. These changes in preferences trigger adaptive evolution; indeed, 32 (46 per cent) of these sites experienced strong positive selection at least in one of the subtypes. At some of the sites, changes in amino acid preferences may be associated with differences in immune escape between subtypes. The prevalence of an amino acid in a protein site within a subtype is only a poor predictor for whether this amino acid is preferred in this subtype according to the phylogenetic analysis. Therefore, attempts to identify the factors of viral evolution from comparative genomics data should integrate across multiple sources of information.

Evolution of olfactory receptor superfamily in bats based on high throughput molecular modelling.

The origin of flight and laryngeal echolocation in bats is likely to have been accompanied by evolutionary changes in other aspects of their sensory biology. Of all sensory modalities in bats, olfaction is perhaps the least well understood. Olfactory receptors (ORs) function in recognizing odour molecules, with crucial roles in evaluating food, as well as in processing social information. Here we compare OR repertoire sizes across taxa and apply a new pipeline that integrates comparative genome data with protein structure modelling and then we employ molecular docking techniques with small molecules to analyse OR functionality based on binding energies. Our results suggest a sharp contraction in odorant recognition of the functional OR repertoire during the origin of bats, consistent with a reduced dependence on olfaction. We also compared bat lineages with contrasting different ecological characteristics and found evidence of differences in OR gene expansion and contraction, and in the composition of ORs with different tuning breadths. The strongest binding energies of ORs in non-echolocating fruit-eating bats were seen to correspond to ester odorants, although we did not detect a quantitative advantage of functional OR repertoires in these bats compared with echolocating insectivorous species. Overall, our findings based on molecular modelling and computational docking suggest that bats have undergone olfactory evolution linked to dietary adaptation. Our results from extant and ancestral bats help to lay the groundwork for targeted experimental functional tests in the future.

Perspective: Microbial hydrogen metabolism in rock-hosted ecosystems

Hydrogen (H2) is among the most common and widely utilized electron donors in microbial metabolism. This is particularly true for microorganisms that inhabit subsurface environments where H2 concentrations can be high due to H2 generation via one or more abiotic and biotic processes, such as serpentinization, radiolysis, cataclasis, and microbial fermentation. A surge in interest in the exploration for and exploitation of geologic (i.e., white and orange) H2 as a clean low carbon fuel therefore necessitates an evaluation of the influence of microorganisms on its flux and potential recovery from subsurface systems. The widespread application of high throughput metagenomic sequencing approaches to rock-hosted ecosystems now makes it possible to readily identify microorganisms that harbor the potential to metabolize H2 and to predict their mode of coupling H2 oxidation with available oxidants using comparative genomic data from natural samples alone. When combined with several recent reports of measured rates of net microbial H2 consumption in rock-hosted ecosystems, such information provides new perspective on the potential for microorganisms to impact the economics of H2 recovery from geologic systems. In this perspective, the different classes of enzymes that microorganisms use to reversibly oxidize H2 to fuel their energy metabolism are introduced and their distribution in several rock-hosted ecosystems is discussed. A compilation of net microbial H2 oxidation activities in rock-hosted ecosystems is also presented to enable estimates of potential H2 loss from natural or stimulated geologic reservoirs during mining activities, with an example provided from the Samail Ophiolite that indicates >90% of geologic H2 produced could be lost to microbial consumption. Finally, avenues to guide future microbial research in environments where geologic H2 mining is planned are discussed.

Cuticular proteins in codling moth (Cydia pomonella) respond to insecticide and temperature stress

The insect cuticle consists of chitin and cuticular proteins (CPs), which stabilize the body shape and provide an effective physical barrier against the external environment. They are also potential target sites for developing environmentally friendly insect management through the utilization of physiology-based methods. The codling moth, Cydia pomonella, is a pest afflicting fruit orchards worldwide. This study used a comparative genomic approach, whole-genome resequencing, and transcriptome data to understand the role that CPs played in the environmental adaptation of the codling moth. A total of 182 putative CPs were identified in the codling moth genome, which were classified into 12 CP families. 119 CPR genes, including 54 RR-1, 60 RR-2, and 5 RR-3 genes were identified and accounted for 65.4% of the total CPs. Eight and seven gene clusters are formed in RR1 and RR2 subfamily and the ancestor-descendant relationship was explained. Five CPAP genes were highly expressed during the egg stage and exposed to high temperature, which indicated their potential role in aiding codling moth eggs in acclimating to varying external heat conditions. Moreover, six CPs belonging to the CPR and CPLCP families were identified in association with insecticide resistance by population resequencing. Their expression levels increased after exposure to insecticides, suggesting they might be involved in codling moth resistance to the insecticides azinphos-methyl or deltamethrin. Our results provide insight into the evolution of codling moth CPs and their association with high temperature adaptation and insecticide resistance, and provide an additional information required for further analysis of CPs in environmental adaptation.

Dynamics and genetic regulation of macronutrient concentrations during grain development in maize

Nitrogen (N), phosphorus (P), and potassium (K) are essential macronutrients that are crucial not only for maize growth and development, but also for crop yield and quality. The genetic basis of macronutrient dynamics and accumulation during grain filling in maize remains largely unknown. In this study, we evaluated grain N, P, and K concentrations in 206 recombinant inbred lines generated from a cross of DH1M and T877 at six time points after pollination. We then calculated conditional phenotypic values at different time intervals to explore the dynamic characteristics of the N, P, and K concentrations. Abundant phenotypic variations were observed in the concentrations and net changes of these nutrients. Unconditional quantitative trait locus (QTL) mapping revealed 41 non-redundant QTLs, including 17, 16, and 14 for the N, P, and K concentrations, respectively. Conditional QTL mapping uncovered 39 non-redundant QTLs related to net changes in the N, P, and K concentrations. By combining QTL, gene expression, co-expression analysis, and comparative genomic data, we identified 44, 36, and 44 candidate genes for the N, P, and K concentrations, respectively, including GRMZM2G371058 encoding a Dof-type zinc finger DNA-binding family protein, which was associated with the N concentration, and GRMZM2G113967 encoding a CBL-interacting protein kinase, which was related to the K concentration. The results deepen our understanding of the genetic factors controlling N, P, and K accumulation during maize grain development and provide valuable genes for the genetic improvement of nutrient concentrations in maize.

When online citizen science meets teaching: Storyfication of a science discovery game to teach, learn, and contribute to genomic research.

In the last decade, video games became a common vehicle for citizen science initiatives in life science, allowing participants to contribute to real scientific data analysis while learning about it. Since 2010, our scientific discovery game (SDG) Phylo enlists participants in comparative genomic data analysis. It is frequently used as a learning tool, but the activities were difficult to aggregate to build a coherent teaching activity. Here, we describe a strategy and series of recipes to facilitate the integration of SDGs in courses and implement this approach in Phylo. We developed new roles and functionalities enabling instructors to create assignments and monitor the progress of students. A story mode progressively introduces comparative genomics concepts, allowing users to learn and contribute to the analysis of real genomic sequences. Preliminary results from a user study suggest this framework may help to boost user motivation and clarify pedagogical objectives.

Assessing the quality of comparative genomics data and results with the cogeqc R/Bioconductor package

Abstract Comparative genomics has become an indispensable part of modern biology due to the advancements in high‐throughput sequencing technologies and the accumulation of genomic data in public databases. However, the quality of genomic data and the choice of parameters used in software tools used for comparative genomics can greatly impact the accuracy of results. Here, we present cogeqc, an R/Bioconductor package that provides researchers with a toolkit to assess genome assembly and annotation quality, orthogroup inference, and synteny detection. The package offers context‐guided assessments of assembly and annotation statistics by comparing observed statistics to those of closely‐related species on NCBI. To assess orthogroup inference, cogeqc calculates a protein domain‐aware orthogroup score that aims at maximising the number of shared protein domains within the same orthogroup. The assessment of synteny detection consists in representing anchor gene pairs as a synteny network and analysing its graph properties, such as clustering coefficient, node count, and scale‐free topology fit. The application of cogeqc to real datasets allowed for an evaluation of multiple parameter combinations for orthogroup inference and synteny detection, providing researchers in need for comparative genomics with guidelines to aid in the selection of the most appropriate tools and parameters for their specific data. We demonstrate that the default parameters in orthogroup identification and synteny detection tools are not always the most suitable, highlighting the importance of performing assessments for each dataset. The assessment metrics provided by cogeqc will help researchers generate more accurate and reliable results.

TBtools-II: A “one for all, all for one” bioinformatics platform for biological big-data mining

Since the official release of the stand-alone bioinformatics toolkit TBtools in 2020, its superior functionality in data analysis has been demonstrated by its widespread adoption by many thousands of users and references in more than 5000 academic articles. Now, TBtools is a commonly used tool in biological laboratories. Over the past 3 years, thanks to invaluable feedback and suggestions from numerous users, we have optimized and expanded the functionality of the toolkit, leading to the development of an upgraded version—TBtools-II. In this upgrade, we have incorporated over 100 new features, such as those for comparative genomics analysis, phylogenetic analysis, and data visualization. Meanwhile, to better meet the increasing needs of personalized data analysis, we have launched the plugin mode, which enables users to develop their own plugins and manage their selection, installation, and removal according to individual needs. To date, the plugin store has amassed over 50 plugins, with more than half of them being independently developed and contributed by TBtools users. These plugins offer a range of data analysis options including co-expression network analysis, single-cell data analysis, and bulked segregant analysis sequencing data analysis. Overall, TBtools is now transforming from a stand-alone software to a comprehensive bioinformatics platform of a vibrant and cooperative community in which users are also developers and contributors. By promoting the theme “one for all, all for one”, we believe that TBtools-II will greatly benefit more biological researchers in this big-data era.

Evolutionary Shortcuts via Multinucleotide Substitutions and Their Impact on Natural Selection Analyses.

Inference and interpretation of evolutionary processes, in particular of the types and targets of natural selection affecting coding sequences, are critically influenced by the assumptions built into statistical models and tests. If certain aspects of the substitution process (even when they are not of direct interest) are presumed absent or are modeled with too crude of a simplification, estimates of key model parameters can become biased, often systematically, and lead to poor statistical performance. Previous work established that failing to accommodate multinucleotide (or multihit, MH) substitutions strongly biases dN/dS-based inference towards false-positive inferences of diversifying episodic selection, as does failing to model variation in the rate of synonymous substitution (SRV) among sites. Here, we develop an integrated analytical framework and software tools to simultaneously incorporate these sources of evolutionary complexity into selection analyses. We found that both MH and SRV are ubiquitous in empirical alignments, and incorporating them has a strong effect on whether or not positive selection is detected (1.4-fold reduction) and on the distributions of inferred evolutionary rates. With simulation studies, we show that this effect is not attributable to reduced statistical power caused by using a more complex model. After a detailed examination of 21 benchmark alignments and a new high-resolution analysis showing which parts of the alignment provide support for positive selection, we show that MH substitutions occurring along shorter branches in the tree explain a significant fraction of discrepant results in selection detection. Our results add to the growing body of literature which examines decades-old modeling assumptions (including MH) and finds them to be problematic for comparative genomic data analysis. Because multinucleotide substitutions have a significant impact on natural selection detection even at the level of an entire gene, we recommend that selection analyses of this type consider their inclusion as a matter of routine. To facilitate this procedure, we developed, implemented, and benchmarked a simple and well-performing model testing selection detection framework able to screen an alignment for positive selection with two biologically important confounding processes: site-to-site synonymous rate variation, and multinucleotide instantaneous substitutions.

Integrated post-genomic cell wall analysis reveals floating biofilm formation associated with high expression of flocculins in the pathogen Pichia kudriavzevii.

The pathogenic yeast Pichia kudriavzevii, previously known as Candida krusei, is more distantly related to Candida albicans than clinically relevant CTG-clade Candida species. Its cell wall, a dynamic organelle that is the first point of interaction between pathogen and host, is relatively understudied, and its wall proteome remains unidentified to date. Here, we present an integrated study of the cell wall in P. kudriavzevii. Our comparative genomic studies and experimental data indicate that the general structure of the cell wall in P. kudriavzevii is similar to Saccharomyces cerevisiae and C. albicans and is comprised of β-1,3-glucan, β-1,6-glucan, chitin, and mannoproteins. However, some pronounced differences with C. albicans walls were observed, for instance, higher mannan and protein levels and altered protein mannosylation patterns. Further, despite absence of proteins with high sequence similarity to Candida adhesins, protein structure modeling identified eleven proteins related to flocculins/adhesins in S. cerevisiae or C. albicans. To obtain a proteomic comparison of biofilm and planktonic cells, P. kudriavzevii cells were grown to exponential phase and in static 24-h cultures. Interestingly, the 24-h static cultures of P. kudriavzevii yielded formation of floating biofilm (flor) rather than adherence to polystyrene at the bottom. The proteomic analysis of both conditions identified a total of 33 cell wall proteins. In line with a possible role in flor formation, increased abundance of flocculins, in particular Flo110, was observed in the floating biofilm compared to exponential cells. This study is the first to provide a detailed description of the cell wall in P. kudriavzevii including its cell wall proteome, and paves the way for further investigations on the importance of flor formation and flocculins in the pathogenesis of P. kudriavzevii.

SyntenyViewer: a comparative genomics-driven translational research tool.

SyntenyViewer is a public web-based tool relying on a relational database available at https://urgi.versailles.inrae.fr/synteny delivering comparative genomics data and associated reservoir of conserved genes between angiosperm species for both fundamental (evolutionary studies) and applied (translational research) applications. SyntenyViewer is made available for (i) providing comparative genomics data for seven major botanical families of flowering plants, (ii) delivering a robust catalog of 103 465 conserved genes between 44 species and inferred ancestral genomes, (iii) allowing us to investigate the evolutionary fate of ancestral genes and genomic regions in modern species through duplications, inversions, deletions, fusions, fissions and translocations, (iv) use as a tool to conduct translational research of key trait-related genes from model species to crops and (v) offering to host any comparative genomics data following simplified procedures and formats Database URL https://urgi.versailles.inrae.fr/synteny.

Impact of the Dimethyl Sulfoxide Reductase Superfamily on the Evolution of Biogeochemical Cycles.

The dimethyl sulfoxide reductase (or MopB) family is a diverse assemblage of enzymes found throughout Bacteria and Archaea. Many of these enzymes are believed to have been present in the last universal common ancestor (LUCA) of all cellular lineages. However, gaps in knowledge remain about how MopB enzymes evolved and how this diversification of functions impacted global biogeochemical cycles through geologic time. In this study, we perform maximum likelihood phylogenetic analyses on manually curated comparative genomic and metagenomic data sets containing over 47,000 distinct MopB homologs. We demonstrate that these enzymes constitute a catalytically and mechanistically diverse superfamily defined not by the molybdopterin- or tungstopterin-containing [molybdopterin or tungstopterin bis(pyranopterin guanine dinucleotide) (Mo/W-bisPGD)] cofactor but rather by the structural fold that binds it in the protein. Our results suggest that major metabolic innovations were the result of the loss of the metal cofactor or the gain or loss of protein domains. Phylogenetic analyses also demonstrated that formate oxidation and CO2 reduction were the ancestral functions of the superfamily, traits that have been vertically inherited from the LUCA. Nearly all of the other families, which drive all other biogeochemical cycles mediated by this superfamily, originated in the bacterial domain. Thus, organisms from Bacteria have been the key drivers of catalytic and biogeochemical innovations within the superfamily. The relative ordination of MopB families and their associated catalytic activities emphasize fundamental mechanisms of evolution in this superfamily. Furthermore, it underscores the importance of prokaryotic adaptability in response to the transition from an anoxic to an oxidized atmosphere. IMPORTANCE The MopB superfamily constitutes a repertoire of metalloenzymes that are central to enduring mysteries in microbiology, from the origin of life and how microorganisms and biogeochemical cycles have coevolved over deep time to how anaerobic life adapted to increasing concentrations of O2 during the transition from an anoxic to an oxic world. Our work emphasizes that phylogenetic analyses can reveal how domain gain or loss events, the acquisition of novel partner subunits, and the loss of metal cofactors can stimulate novel radiations of enzymes that dramatically increase the catalytic versatility of superfamilies. We also contend that the superfamily concept in protein evolution can uncover surprising kinships between enzymes that have remarkably different catalytic and physiological functions.

Barbel regeneration and function divergence in red-tail catfish (Hemibagrus wyckioides) based on the chromosome-level genomes and comparative transcriptomes

Catfish (Siluriformes) are one of the most diverse vertebrate orders and are characterized by whisker-like barbels, which are important sensory organs in most of teleosts. However, their specific biological functions are still unclear. Red-tail catfish (Hemibagrus wyckioides) is well-known catfish species with four pairs of barbels, of which the maxillary barbels reach two-thirds of the body length. In this study, a 776.58 Mb high-quality chromosome-level genome was assembled into 29 chromosomes. Comparative genome data indicated that the barbeled regeneration gene ccl33 has expanded into 11 tandemly duplicated copies. Transcriptome data revealed the functional differentiation of different barbels and suggested that the maxillary barbel might be necessary for water temperature perception. Taste receptor genes were also characterized in teleosts with different food habits. Selection pressures were revealed to affect the sugar-based solute transport domain of the sweet taste receptor gene t1r2 in carnivorous fishes. In addition, the bitter taste receptor gene t2r200 was found to be lost from the genomes of four catfish species. Therefore, our study provides a genomic foundation for understanding the regeneration and functional differentiation of barbels in red-tail catfish and also reveals novel insights into the feeding evolution of fish species with different feeding habits.

MycoCosm, the JGI's Fungal Genome Portal for Comparative Genomic and Multiomics Data Analyses.

MycoCosm ( https://mycocosm.jgi.doe.gov/ ) is an integrated fungal genomics portal that currently includes over 2000 fungal genomes. Efficiently exploring these genomes allows the scientific community to address challenges associated with energy and the environment. Here, we provide examples and guidelines for navigating around MycoCosm, and for using a variety of analysis tools to compare genomics and other "omics" data from the fungus Neocallimastix californiae with its relatives.

In Silico Genome-Scale Analysis of Molecular Mechanisms Contributing to the Development of a Persistent Infection with Methicillin-Resistant Staphylococcus aureus (MRSA) ST239.

The increasing frequency of isolation of methicillin-resistant Staphylococcus aureus (MRSA) limits the chances for the effective antibacterial therapy of staphylococcal diseases and results in the development of persistent infection such as bacteremia and osteomyelitis. The aim of this study was to identify features of the MRSAST239 0943-1505-2016 (SA943) genome that contribute to the formation of both acute and chronic musculoskeletal infections. The analysis was performed using comparative genomics data of the dominant epidemic S. aureus lineages, namely ST1, ST8, ST30, ST36, and ST239. The SA943 genome encodes proteins that provide resistance to the host's immune system, suppress immunological memory, and form biofilms. The molecular mechanisms of adaptation responsible for the development of persistent infection were as follows: amino acid substitution in PBP2 and PBP2a, providing resistance to ceftaroline; loss of a large part of prophage DNA and restoration of the nucleotide sequence of beta-hemolysin, that greatly facilitates the escape of phagocytosed bacteria from the phagosome and formation of biofilms; dysfunction of the AgrA system due to the presence of psm-mec and several amino acid substitutions in the AgrC; partial deletion of the nucleotide sequence in genomic island vSAβ resulting in the loss of two proteases of Spl-operon; and deletion of SD repeats in the SdrE amino acid sequence.

Genomic islands and their role in fitness traits of two key sepsis-causing bacterial pathogens.

To survive and establish a niche for themselves, bacteria constantly evolve. Toward that, they not only insert point mutations and promote illegitimate recombinations within their genomes but also insert pieces of 'foreign' deoxyribonucleic acid, which are commonly referred to as 'genomic islands' (GEIs). The GEIs come in several forms, structures and types, often providing a fitness advantage to the harboring bacterium. In pathogenic bacteria, some GEIs may enhance virulence, thus altering disease burden, morbidity and mortality. Hence, delineating (i) the GEIs framework, (ii) their encoded functions, (iii) the triggers that help them move, (iv) the mechanisms they exploit to move among bacteria and (v) identification of their natural reservoirs will aid in superior tackling of several bacterial diseases, including sepsis. Given the vast array of comparative genomics data, in this short review, we provide an overview of the GEIs, their types and the compositions therein, especially highlighting GEIs harbored by two important pathogens, viz. Acinetobacter baumannii and Klebsiella pneumoniae, which prominently trigger sepsis in low- and middle-income countries. Our efforts help shed some light on the challenges these pathogens pose when equipped with GEIs. We hope that this review will provoke intense research into understanding GEIs, the cues that drive their mobility across bacteria and the ways and means to prevent their transfer, especially across pathogenic bacteria.