The genome of Yersinia enterocolitica is the most stable of the three pathogenic species.
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DNA, Bacterial↗
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A human-curated annotation of the Candida albicans genome.
Recent sequencing and assembly of the genome for the fungal pathogen Candida albicans used simple automated procedures for the identification of putative genes. We have reviewed the entire assembly, both by hand and with additional bioinformatic resources, to accurately map and describe 6,354 genes and to identify 246 genes whose original database entries contained sequencing errors (or possibly mutations) that affect their reading frame. Comparison with other fungal genomes permitted the identification of numerous fungus-specific genes that might be targeted for antifungal therapy. We also observed that, compared to other fungi, the protein-coding sequences in the C. albicans genome are especially rich in short sequence repeats. Finally, our improved annotation permitted a detailed analysis of several multigene families, and comparative genomic studies showed that C. albicans has a far greater catabolic range, encoding respiratory Complex 1, several novel oxidoreductases and ketone body degrading enzymes, malonyl-CoA and enoyl-CoA carriers, several novel amino acid degrading enzymes, a variety of secreted catabolic lipases and proteases, and numerous transporters to assimilate the resulting nutrients. The results of these efforts will ensure that the Candida research community has uniform and comprehensive genomic information for medical research as well as for future diagnostic and therapeutic applications.
Journal Article↗
Whole genome sequencing and phylogenetic classification accelerate the implementation of respiratory syncytial virus genomic surveillance in Canada: a pilot study.
UNLABELLED: Whole genome sequencing (WGS) has emerged as a powerful tool to facilitate the study of existing and emerging infectious diseases. WGS-based genomic surveillance provides information on the genetic diversity and tracks the evolution of important viral pathogens, including respiratory syncytial virus (RSV). Multiplex tiling polymerase chain reaction (PCR) assays have been used to facilitate sequencing of a variety of pathogens in support of genomics-based surveillance initiatives. We developed, optimized, and implemented multiplex tiling PCR assays for RSVA and RSVB capable of generating near-complete genomes in the majority of contemporaneous specimens tested. A pilot data set comprising 52 RSVA and 37 RSVB genomes derived from Canadian clinical specimens during the 2022-2023 respiratory virus season was used to perform phylogenetic analyses using both near-complete genome and glycoprotein (G) sequences. Overall, the RSV phylogenetic tree built with whole genomes showed identical lineage clusters as compared to the G gene but was more discriminatory. Moreover, the availability of complete genomes enables the identification of a broader range of mutations. For instance, mutations identified in the fusion protein among Canadian isolates tested here, including S377N, K272M, S276N, S211N, S206I, and S209Q, could affect the efficacy of current vaccines or antiviral-based therapeutics. In conclusion, our work reinforces other recent studies demonstrating the utility of multiplex tiling PCR assays to facilitate high-throughput WGS of RSV, which is capable of supporting enhanced genomic surveillance initiatives, as well as the more comprehensive genomic analyses required to inform public health strategies for the development and usage of vaccines and antiviral drugs. IMPORTANCE: We present assays to efficiently sequence genomes of RSVA and RSVB. This enables researchers and public health agencies to acquire high-quality genomic data using rapid and cost-effective approaches. Genomic data-based comparative analysis can be used to conduct surveillance and monitor circulating isolates for efficacy of vaccines and antiviral therapeutics.
Humans↗
Integrated approaches for detection of plant pathogenic bacteria and diagnosis of bacterial diseases.
Disease diagnosis is based on a number of factors, including laboratory tests for pathogen identification. Rapid development of genomic techniques for characterization of bacteria over the past decade has greatly simplified and improved pathogen detection and identification, but DNA-based methods have not yet entirely replaced traditional culture and phenotypic tests in the plant industry. The first section of this review focuses on rapid immunodiagnostic and DNA-based detection methods for known bacterial pathogens in plants or plant products, which often manifest no symptoms of disease. The second section covers the broader topic of disease diagnosis and new methods for identifying and characterizing bacteria.
Animals↗
Putative homeodomain proteins identified in prokaryotes based on pattern and sequence similarity.
A putative homeodomain has been identified in eubacterial genomes, which include several pathogens. The domain is related in sequence to homeodomain, a component specific to transcription factors and playing a very important role in eukaryotes such as controlling the developmental processes of the organism. The putative homeodomain has been characterized utilizing the eukaryotic homeodomain protein sequence signature present in PROSITE as well as the sequence similarity search using BLAST suite for different eubacterial genomes. These findings provide evidence for the occurrence of DNA-binding motif in prokarya similar to that in eukarya.
Amino Acid Sequence↗
A comprehensive view on proteasomal sequences: implications for the evolution of the proteasome.
Proteasomes are large multimeric self-compartmentizing proteases, which play a crucial role in the clearance of misfolded proteins, breakdown of regulatory proteins, processing of proteins by specific partial proteolysis, cell cycle control as well as preparation of peptides for immune presentation. Two main types can be distinguished by their different tertiary structure: the 20S proteasome and the proteasome-like heat shock protein encoded by heat shock locus V, hslV. Usually, each biological kingdom is characterized by its specific type of proteasome. The 20S proteasomes occur in eukarya and archaea whereas hslV protease is prevalent in bacteria. To verify this rule we applied a genome-wide sequence search to identify proteasomal sequences in data of finished and yet unfinished genome projects. We found several exceptions to this paradigm: (1) Protista: in addition to the 20S proteasome, Leishmania, Trypanosoma and Plasmodium contained hslV, which may have been acquired from an alpha-proteobacterial progenitor of mitochondria. (2) Bacteria: for Magnetospirillum magnetotacticum and Enterococcus faecium we found that each contained two distinct hslVs due to gene duplication or horizontal transfer. Including unassembled data into the analyses we confirmed that a number of bacterial genomes do not contain any proteasomal sequence due to gene loss. (3) High G+C Gram-positives: we confirmed that high G+C Gram-positives possess 20S proteasomes rather than hslV proteases. The core of the 20S proteasome consists of two distinct main types of homologous monomers, alpha and beta, which differentiated into seven subtypes by further gene duplications. By looking at the genome of the intracellular pathogen Encephalitozoon cuniculi we were able to show that differentiation of beta-type subunits into different subtypes occurred earlier than that of alpha-subunits. Additionally, our search strategy had an important methodological consequence: a comprehensive sequence search for a particular protein should also include the raw sequence data when possible because proteins might be missed in the completed assembled genome. The structure-based multiple proteasomal alignment of 433 sequences from 143 organisms can be downloaded from the URL dagger and will be updated regularly.
Amino Acid Sequence↗
Comparative genome analysis of the alpha -proteobacteria: relationships between plant and animal pathogens and host specificity.
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Agrobacterium tumefaciens↗
Identification of a 35-kilodalton serovar-cross-reactive flagellar protein, FlaB, from Leptospira interrogans by N-terminal sequencing, gene cloning, and sequence analysis.
During the screening of antibodies to pathogenic leptospires, a murine monoclonal antibody (designated M138) was found to react with various serovars. An antigen of approximately 35 kDa from Leptospira interrogans serovar pomona, which reacted strongly with M138, was characterized by N-terminal amino acid sequencing and identified as a flagellin, a class B polypeptide subunit (FlaB) of the periplasmic flagella. The gene encoding the FlaB protein, flaB, was amplified from the genomic DNA of several pathogenic serovars by PCR with a single pair of oligonucleotide primers, suggesting that FlaB is highly conserved among these serovars. Cloning and sequence analysis of flaB from serovar pomona revealed that it contains an 849-bp open reading frame with a G + C content of 46.88% which encodes a 283-amino-acid protein with a calculated molecular mass of 31.297 kDa and a predicted pI of 9.065. A sequence comparison of flagellin proteins revealed that the amino acid sequence is most variable in the central portion of the serovar pomona FlaB, which is believed to contain specific sequence information and which may thus be useful in the design of DNA or synthetic peptide probes suitable for the detection of infection with pathogenic leptospires.
Amino Acid Sequence↗
Serial analysis of gene expression in eukaryotic pathogens.
The tag-based method of serial analysis of gene expression (SAGE) has been used to measure mRNA abundance and differential expression in a variety of organisms including several parasites and fungal pathogens. SAGE is based on the collection of short sequence tags as a measure of transcript abundance and the method provides an alternative, and in some instances, complementary approach to array-based methods of measuring differential gene expression. These methods are being used to improve our molecular understanding of the pathogenesis of eukaryotic microbes and SAGE in particular presents valuable opportunities for gene discovery and genome annotation. For eukaryotic pathogens, the SAGE method has been employed for the parasites Plasmodium falciparum, Toxoplasma gondii and Giardia lamblia, as well as fungal pathogens of plants (Magnaporthe grisea, Blumeria graminis, Ustilago maydis) and humans (Cryptococcus neoformans, Coccidiodes posadasii, Trichophyton rubrum). The accumulating information promises to speed the identification of key pathogen functions for virulence and proliferation in the host with the hope that some of these will represent important targets for drug and vaccine development.
Animals↗
A bacteriophage encoding a pathogenicity island, a type-IV pilus and a phage receptor in cholera bacteria.
The virulence properties of many pathogenic bacteria are due to proteins encoded by large gene clusters called pathogenicity islands, which are found in a variety of human pathogens including Escherichia coli, Salmonella, Shigella, Yersinia, Helicobacter pylori, Vibrio cholerae, and animal and plant pathogens such as Dichelobacter nodosus and Pseudomonas syringae. Although the presence of pathogenicity islands is a prerequisite for many bacterial diseases, little is known about their origins or mechanism of transfer into the bacterium. The bacterial agent of epidemic cholera, Vibrio cholerae, contains a bacteriophage known as cholera-toxin phage (CTXphi), which encodes the cholera toxin, and a large pathogenicity island called the VPI (for V. cholerae pathogenicity island) which itself encodes a toxin-coregulated pilus that functions as a colonization factor and as a CTXphi receptor. We have now identified the VPI pathogenicity island as the genome of another filamentous bacteriophage, VPIphi. We show that VPIphi is transferred between V. cholerae strains and provide evidence that the TcpA subunit of the toxin-coregulated type IV pilus is in fact a coat protein of VPIphi. Our results are the first description of a phage that encodes a receptor for another phage and of a virus-virus interaction that is necessary for bacterial pathogenicity.
Bacterial Outer Membrane Proteins↗
The protein secretion systems in Listeria: inside out bacterial virulence.
Listeria monocytogenes, the etiologic agent of listeriosis, remains a serious public health concern with its frequent occurrence in food coupled with a high mortality rate. The capacity of a bacterium to secrete proteins to or beyond the bacterial cell surface is of crucial importance in the understanding of biofilm formation and bacterial pathogenesis to further develop defensive strategies. Recent findings in protein secretion in Listeria together with the availability of complete genome sequences of several pathogenic L. monocytogenes strains, as well as nonpathogenic Listeria innocua Clip11262, prompted us to summarize the listerial protein secretion systems. Protein secretion would rely essentially on the Sec (Secretion) pathway. The twin-arginine translocation pathway seems encoded in all but one sequenced Listeria. In addition, a functional flagella export apparatus, a fimbrilin-protein exporter, some holins and a WXG100 secretion system are encoded in listerial genomes. This critical review brings new insights into the physiology and virulence of Listeria species.
Bacterial Proteins↗
Microarray-based resequencing of multiple Bacillus anthracis isolates.
We used custom-designed resequencing arrays to generate 3.1 Mb of genomic sequence from a panel of 56 Bacillus anthracis strains. Sequence quality was shown to be very high by replication (discrepancy rate of 7.4 x 10(-7)) and by comparison to independently generated shotgun sequence (discrepancy rate < 2.5 x 10(-6)). Population genomics studies of microbial pathogens using rapid resequencing technologies such as resequencing arrays are critical for recognizing newly emerging or genetically engineered strains.
Bacillus anthracis↗
A new family of highly variable proteins in the Chlamydophila pneumoniae genome.
Chlamydiaceae are obligate intracellular bacterial pathogens characterized by a wide range of vertebrate host, tissue tropism and spectrum of diseases. To get insights into the biological mechanisms involved in these differences, we have put forward a computational and experimental procedure to identify the genome recombination hotspots, as frequent sequence variation allows rapid adaptation to environmental changes. We find a larger potential for recombination in Chlamydophila pneumoniae genomes as compared with Chlamydia trachomatis or Chlamydia muridarum. Such potential is mostly concentrated in a family of seven previously uncharacterized species-specific elements that we named ppp for C.pneumoniae polymorphic protein genes, which have the potential to vary by homologous recombination and slipped-mispair. Experimentally, we show that these sequences are indeed highly polymorphic among a collection of nine C.pneumoniae strains of very diverse geographical and pathological origins, mainly by slippage of a poly(C) tract. We also show that most elements are transcribed during infection. In silico analyses suggest that Ppps correspond to outer membrane proteins. Given their species specificity, their putative location in the outer membrane and their extreme polymorphism, Ppps are most likely to be important in the pathogenesis of C.pneumoniae and could represent targets for future vaccine development.
Bacterial Outer Membrane Proteins↗
A phenotypic paradigm for cerebral palsy genetics.
Cerebral palsy (CP) represents a clinically and etiologically heterogeneous group of permanent but not unchanging disorders of movement, posture, and motor function resulting from non-progressive disturbances of the developing fetal or infant brain. Pathogenic variants in Mendelian disease-associated genes can be found in a subset of individuals with CP, with variants deemed causal of CP having been published for at least 515 genes. Currently, controversy exists as to whether to interpret such pathogenic variants as causing CP, whether the diagnosis instead should be "CP mimic," or whether a clinical diagnosis of CP should coexist with the molecular diagnosis of a Mendelian disease. Accordingly, there is no universally accepted model of the genetic architecture of CP. Here, we present a statistical approach that treats CP as a phenotypic feature for which some genetic disorders confer an increased risk. Based on comprehensive literature curation, we show that the null hypothesis of no CP association can be rejected for only 89 of the 515 genes. We applied these findings to the analysis of a cohort of 460 children diagnosed with CP in the Shriner Children's network who underwent genome sequencing. We identified pathogenic or likely pathogenic (P/LP) variants in 60 genes in 15.8% of the children. Only 16 of the 60 genes had significant evidence for CP association in our literature analysis. Our results suggest that a stratified approach to attributing causality to genetic variants in CP could support precision genomic medicine for affected individuals.
Humans↗
What can bacterial genome research teach us about bacteria-plant interactions?
Biological research is changing dramatically. Genomic and post-genomic research is responsible for the accumulation of enormous datasets, which allow the formation of holistic views of the organisms under investigation. In the field of microbiology, bacteria represent ideal candidates for this new development. It is relatively easy to sequence the genomes of bacteria, to analyse their transcriptomes and to collect information at the proteomic level. Genome research on symbiotic, pathogenic and associative bacteria is providing important information on bacteria-plant interactions, especially on type-III secretion systems (TTSS) and their role in the interaction of bacteria with plants.
Bacteria↗
Novel G-protein-coupled receptor-like proteins in the plant pathogenic fungus Magnaporthe grisea.
BACKGROUND: The G-protein-coupled receptors (GPCRs) are one of the largest protein families in human and other animal genomes, but no more than 10 GPCRs have been characterized in fungi. Do fungi contain only this handful or are there more receptors to be discovered? We asked this question using the recently sequenced genome of the fungal plant pathogen Magnaporthe grisea. RESULTS: Proteins with significant similarity to fungus-specific and other eukaryotic GPCRs were identified in M. grisea. These included homologs of known fungal GPCRs, the cAMP receptors from Dictyostelium, and a steroid receptor mPR. We also identified a novel class of receptors typified by PTH11, a cell-surface integral membrane protein required for pathogenicity. PTH11 has seven transmembrane regions and an amino-terminal extracellular cysteine-rich EGF-like domain (CFEM domain), a characteristic also seen in human GPCRs. Sixty-one PTH11-related proteins were identified in M. grisea that shared a common domain with homologs in Neurospora crassa and other fungi belonging to this subphylum of the Ascomycota (the Pezizomycotina). None was detected in other fungal groups (Basidiomycota or other Ascomycota subphyla, including yeasts) or any other eukaryote. The subclass of PTH11 containing the CFEM domain is highly represented in M. grisea. CONCLUSION: In M. grisea we identified homologs of known GPCRs and a novel class of GPCR-like receptors specific to filamentous ascomycetes. A member of this new class, PTH11, is required for pathogenesis, thus suggesting roles in pathogenicity for other members. The identified classes constitute the largest number of GPCR-like proteins reported in fungi to date.
Amino Acid Sequence↗
Patterns of antimicrobial resistance genes in pathogens across One Health sectors in Ireland: an in silico approach.
As part of a rapid risk assessment, an in silico approach was used to detect antimicrobial resistance (AMR) in pathogenic isolates from humans, animals, and the environment. A total of 11,670 genomic data sets were retrieved from the NCBI Pathogen Detection system for Ireland, which represented 47 pathogenic species, including Salmonella enterica, Escherichia coli/Shigella spp., Staphylococcus aureus, Klebsiella pneumoniae, and Enterococcus faecium. Identifying the most critical pathogenic strains over time is essential, as these organisms significantly contribute to mortality, morbidity, and hospitalization. The analysis identified 799 antimicrobial resistance genes (ARGs), including their allelic diversity, 117 plasmid replicons, and 274 virulence factors. Several critical ARGs, particularly those conferring resistance to beta-lactams, aminoglycosides, quinolones, and colistin, were common across isolates originating from human, animal, and environmental sources, suggesting shared resistance profiles across One Health sectors. Klebsiella pneumoniae, E. coli/Shigella spp., S. enterica, and S. aureus were the dominant hosts of these ARGs and associated mobile genetic elements. Increasing resistance across major antibiotic classes aligned with trends reported across other European countries. This study provides a national-scale in silico comparison of AMR across pathogens and One Health sectors using publicly available genomic data. The findings help reinforce Ireland's AMR surveillance by showing which resistance genes are present and how they spread across critical pathogens in humans, animals, and the environment. These findings highlight the urgent need for improved antibiotic stewardship and integrated One Health surveillance to limit the emergence and spread of AMR.IMPORTANCEAntimicrobial resistance (AMR) is a growing threat to human, animal, and environmental health. This study used publicly available genomic data to identify antimicrobial resistance genes (ARGs) in key bacterial pathogens circulating in Ireland. By analyzing over 11,000 genomes from humans, animals, and the environment, we found that several dangerous resistance genes, including those against last-resort antibiotics, were widespread across different sources. The study highlights which bacteria and resistance genes are most critical and how they may spread between humans, animals, and the environment. These insights provide a national snapshot of AMR, supporting more effective monitoring and prevention strategies. By revealing patterns of resistance and modes of transmission, our findings underscore the importance of coordinated antibiotic stewardship and One Health approaches to slow the emergence and spread of resistant infections, protecting public health and ensuring antibiotics remain effective.
Humans↗
Identification of insertion hot spots for non-LTR retrotransposons: computational and biochemical application to Entamoeba histolytica.
The genome of the human pathogen Entamoeba histolytica contains non-long terminal repeat (LTR) retrotransposons, the EhLINEs and EhSINEs, which lack targeted insertion. We investigated the importance of local DNA structure, and sequence preference of the element-encoded endonuclease (EN) in selecting target sites for retrotransposon insertion. Pre-insertion loci were tested computationally to detect unique features based on DNA structure, thermodynamic considerations and protein interaction measures. Target sites could readily be distinguished from other genomic sites based on these criteria. The contribution of the EhLINE1-encoded EN in target site selection was investigated biochemically. The sequence-specificity of the EN was tested in vitro with a variety of mutated substrates. It was possible to assign a consensus sequence, 5'-GCATT-3', which was efficiently nicked between A-T and T-T. The upstream G residue enhanced EN activity, possibly serving to limit retrotransposition in the A+T-rich E.histolytica genome. Mutated substrates with poor EN activity showed structural differences compared with normal substrates. Analysis of retrotransposon insertion sites from a variety of organisms showed that, in general, regions of favorable DNA structure were recognized for retrotransposition. A combination of favorable DNA structure and preferred EN nicking sequence in the vicinity of this structure may determine the genomic hotspots for retrotransposition.
Animals↗