Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Pathogen genomics”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 451 records · Page 25Linked to original sources

The complete genome sequence of the murine respiratory pathogen Mycoplasma pulmonis.

Mycoplasma pulmonis is a wall-less eubacterium belonging to the Mollicutes (trivial name, mycoplasmas) and responsible for murine respiratory diseases. The genome of strain UAB CTIP is composed of a single circular 963 879 bp chromosome with a G + C content of 26.6 mol%, i.e. the lowest reported among bacteria, Ureaplasma urealyticum apart. This genome contains 782 putative coding sequences (CDSs) covering 91.4% of its length and a function could be assigned to 486 CDSs whilst 92 matched the gene sequences of hypothetical proteins, leaving 204 CDSs without significant database match. The genome contains a single set of rRNA genes and only 29 tRNAs genes. The replication origin oriC was localized by sequence analysis and by using the G + C skew method. Sequence polymorphisms within stretches of repeated nucleotides generate phase-variable protein antigens whilst a recombinase gene is likely to catalyse the site-specific DNA inversions in major M.pulmonis surface antigens. Furthermore, a hemolysin, secreted nucleases and a glyco-protease are predicted virulence factors. Surprisingly, several of the genes previously reported to be essential for a self-replicating minimal cell are missing in the M.pulmonis genome although this one is larger than the other mycoplasma genomes fully sequenced until now.

Animals↗

Bacterial genomes pave the way to novel vaccines.

The availability of complete genome sequences of pathogens has dramatically changed the scope for developing improved and novel vaccines by increasing the speed of target identification. Genomics-based technologies have many advantages, compared to conventional approaches, which are time-consuming and usually identify only abundant antigens that are expressible under in vitro culture conditions. This review focuses on recent reports of genomics-based strategies that can be applied to most pathogens and that exploit genome sequence information in alliance with adjunct technologies, including bioinformatics, expression analyses, random mutagenesis or protein/peptide-based selection methods. Despite the caveats that are associated with the individual approaches, these technologies have already made major contributions to the identification and selection of novel vaccine candidates to combat bacterial infections.

Bacterial Infections↗

Unique DNA sequences of avian pathogenic Escherichia coli isolates as determined by genomic suppression subtractive hybridization.

Genomic suppression subtractive hybridization was carried out between an avian pathogenic Escherichia coli (APEC) and an E. coli isolate from apparently healthy poultry (avian fecal E. coli or AFEC) to understand the genomic differences between APEC and AFEC and to identify potential virulence genes. In an effort to ensure that the genes identified were novel, tester and driver strains were chosen by their similarities in certain known virulence genes. In total, 24 subtractive hybridization fragments specific for APEC were obtained. Eight of the fragments were phage or plasmid related, 13 matched to chromosomal regions and three did not show homology to any known genes. We further determined the association of APEC-specific fragments with virulence by screening a collection of APEC, AFEC and human uropathogenic E. coli (UPEC) using the PCR. Chromosomally located fragments that matched to the ireA iron-responsive element gene, the tia invasion determinant gene, the ibeA invasion gene, genes encoding P pili and a gene encoding aldo/keto reductase were present at significantly higher frequencies in APEC and UPEC than in AFEC, suggesting their contribution to the virulence of extraintestinal pathogenic E. coli. No genes were found to be specific to APEC alone.

Animals↗

Analysis of pathogenicity by restriction-endonuclease digestion of amplified genomic DNA of Entamoeba histolytica isolated in Pernambuco, Brazil.

The pathogenicity of 47 strains of Entamoeba histolytica isolated in Pernambuco, Brazil, was examined using the polymerase chain reaction (PCR) followed by restriction-endonuclease digestion. Electrophoretic patterns of PCR products digested with HinfI revealed that all strains were nonpathogenic. The results were entirely in accord with phenotypic properties such as isoenzyme patterns and the failure to bind a pathogenic-isolate-specific monoclonal antibody. When the sensitivity of PCR was examined, amplified products could be detected from template DNA equivalent to five trophozoites. These observations indicate that PCR amplification of genomic DNA and subsequent restriction-enzyme digestion is a useful strategy for obtaining a sensitive and accurate diagnosis. The present study also demonstrates that nonpathogenic strains of E. histolytica predominate in northeastern Brazil.

Animals↗

Reference-Free Variant Calling with Local Graph Construction with ska lo (SKA).

The study of genomic variants is increasingly important for public health surveillance of pathogens. Traditional variant-calling methods from whole-genome sequencing data rely on reference-based alignment, which can introduce biases and require significant computational resources. Alignment- and reference-free approaches offer an alternative by leveraging k-mer-based methods, but existing implementations often suffer from sensitivity limitations, particularly in high mutation density genomic regions. Here, we present ska lo, a graph-based algorithm that aims to identify within-strain variants in pathogen whole-genome sequencing data by traversing a colored De Bruijn graph and building variant groups (i.e. sets of variant combinations). Through in silico benchmarking and real-world dataset analyses, we demonstrate that ska lo achieves high sensitivity in single-nucleotide polymorphism (SNP) calls while also enabling the detection of insertions and deletions, as well as SNP positioning on a reference genome for recombination analyses. These findings highlight ska lo as a simple, fast, and effective tool for pathogen genomic epidemiology, extending the range of reference-free variant-calling approaches. ska lo is freely available as part of the SKA program (https://github.com/bacpop/ska.rust).

Polymorphism, Single Nucleotide↗

The Three-dimensional structure of a superantigen-like protein, SET3, from a pathogenicity island of the Staphylococcus aureus genome.

The staphylococcal enterotoxin-like toxins (SETs) are a family of proteins encoded within the Staphylococcus aureus genome that were identified by their similarity to the well described bacterial superantigens. The first crystal structure of a member of the SET family, SET3, has been determined to 1.9 A (R = 0.205, R(free) = 0.240) and reveals a fold characteristic of the superantigen family but with significant differences. The SET proteins are secreted at varying levels by staphylococcal isolates, and seroconversion studies of normal individuals indicate that they are strongly antigenic to humans. Recombinant SETs do not exhibit any of the properties expected of superantigens such as major histocompatibility complex class II binding or broad T-cell activation, suggesting they have an entirely different function. The fact that the whole gene family is clustered within the pathogenicity island SaIn2 of the S. aureus genome suggests that they are involved in host/pathogen interactions.

Amino Acid Sequence↗

The genome sequence of the entomopathogenic bacterium Photorhabdus luminescens.

Photorhabdus luminescens is a symbiont of nematodes and a broad-spectrum insect pathogen. The complete genome sequence of strain TT01 is 5,688,987 base pairs (bp) long and contains 4,839 predicted protein-coding genes. Strikingly, it encodes a large number of adhesins, toxins, hemolysins, proteases and lipases, and contains a wide array of antibiotic synthesizing genes. These proteins are likely to play a role in the elimination of competitors, host colonization, invasion and bioconversion of the insect cadaver, making P. luminescens a promising model for the study of symbiosis and host-pathogen interactions. Comparison with the genomes of related bacteria reveals the acquisition of virulence factors by extensive horizontal transfer and provides clues about the evolution of an insect pathogen. Moreover, newly identified insecticidal proteins may be effective alternatives for the control of insect pests.

Amino Acid Sequence↗

The molecular basis of infectious diseases: pathogenicity islands and other mobile genetic elements. A review.

Bacterial genomes generally consist of stable regions termed core genome, and variable regions that form the so-called flexible gene pool. The flexible part is composed of bacteriophages, plasmids, transposons as well as unstable large regions that have been termed genomic islands. Genomic islands encoding virulence factors of pathogenic bacteria have been designated "pathogenicity islands". Pathogenicity islands were first discovered in uropathogenic Escherichia coli and presently more than 30 bacterial species carrying pathogenicity islands have been described. This review summarises the current knowledge on bacterial genomic islands and their general features, and discusses their putative role in the evolution of microbes in the light of genomics of pathogenic bacteria.

Animals↗

Concerted evolution in the repeats of an immunomodulating cell surface protein, SOWgp, of the human pathogenic fungi Coccidioides immitis and C. posadasii.

Genome dynamics that allow pathogens to escape host immune responses are fundamental to our understanding of host-pathogen interactions. Here we present the first population-based study of the process of concerted evolution in the repetitive domain of a protein-coding gene. This gene, SOWgp, encodes the immunodominant protein in the parasitic phase of the human pathogenic fungi Coccidioides immitis and C. posadasii. We sequenced the entire gene from strains representing the geographic ranges of the two Coccidioides species. By using phylogenetic and genetic distance analyses we discovered that the repetitive part of SOWgp evolves by concerted evolution, predominantly by the mechanism of unequal crossing over. We implemented a mathematical model originally developed for multigene families to estimate the rate of homogenization and recombination of the repetitive array, and the results indicate that the pattern of concerted evolution is a result of homogenization of repeat units proceeding at a rate close to the nucleotide point mutation rate. The release of the SOWgp molecules by the pathogen during proliferation may mislead the host: we speculate that the pathogen benefits from concerted evolution of repeated domains in SOWgp by an enhanced ability to misdirect the host's immune system.

Antigens, Fungal↗

Whole-genome analyses of speciation events in pathogenic Brucellae.

Despite their high DNA identity and a proposal to group classical Brucella species as biovars of Brucella melitensis, the commonly recognized Brucella species can be distinguished by distinct biochemical and fatty acid characters, as well as by a marked host range (e.g., Brucella suis for swine, B. melitensis for sheep and goats, and Brucella abortus for cattle). Here we present the genome of B. abortus 2308, the virulent prototype biovar 1 strain, and its comparison to the two other human pathogenic Brucella species and to B. abortus field isolate 9-941. The global distribution of pseudogenes, deletions, and insertions supports previous indications that B. abortus and B. melitensis share a common ancestor that diverged from B. suis. With the exception of a dozen genes, the genetic complements of both B. abortus strains are identical, whereas the three species differ in gene content and pseudogenes. The pattern of species-specific gene inactivations affecting transcriptional regulators and outer membrane proteins suggests that these inactivations may play an important role in the establishment of host specificity and may have been a primary driver of speciation in the genus Brucella. Despite being nonmotile, the brucellae contain flagellum gene clusters and display species-specific flagellar gene inactivations, which lead to the putative generation of different versions of flagellum-derived structures and may contribute to differences in host specificity and virulence. Metabolic changes such as the lack of complete metabolic pathways for the synthesis of numerous compounds (e.g., glycogen, biotin, NAD, and choline) are consistent with adaptation of brucellae to an intracellular life-style.

Bacterial Proteins↗

Complementing genomics with proteomics: the membrane subproteome of Pseudomonas aeruginosa PAO1.

With the completion of many genome projects, a shift is now occurring from the acquisition of gene sequence to understanding the role and context of gene products within the genome. The opportunistic pathogen Pseudomonas aeruginosa is one organism for which a genome sequence is now available, including the annotation of open reading frames (ORFs). However, approximately one third of the ORFs are as yet undefined in function. Proteomics can complement genomics, by characterising gene products and their response to a variety of biological and environmental influences. In this study we have established the first two-dimensional gel electrophoresis reference map of proteins from the membrane fraction of P. aeruginosa strain PA01. A total of 189 proteins have been identified and correlated with 104 genes from the P. aeruginosa genome. Annotated membrane proteins could be grouped into three distinct categories: (i) those with functions previously characterised in P. aeruginosa (38%); (ii) those with significant sequence similarity to proteins with assigned function or hypothetical proteins in other organisms (46%); and (iii) those with unknown function (16%). Transmembrane prediction algorithms showed that each identified protein sequence contained at least one membrane-spanning region. Furthermore, the current methodology used to isolate the membrane fraction was shown to be highly specific since no contaminating cytosolic proteins were characterised. Preliminary analysis showed that at least 15 gel spots may be glycosylated in vivo, including three proteins that have not previously been functionally characterised. The reference map of membrane proteins from this organism is now the basis for determining surface molecules associated with antibiotic resistance and efflux, cell-cell signalling and pathogen-host interactions in a variety of P. aeruginosa strains.

Bacterial Proteins↗

MgtC as a horizontally-acquired virulence factor of intracellular bacterial pathogens: evidence from molecular phylogeny and comparative genomics.

MgtC is a virulence factor required for intramacrophage survival and growth in low Mg2+ medium in two pathogens that are not phylogenetically related, Salmonella typhimurium and Mycobacterium tuberculosis. In S. typhimurium, mgtC is carried by the SPI-3 pathogenicity island and hybridization studies have suggested that the distribution of mgtC among enterobacteria is limited. In the present study, we searched for the presence of mgtC-like sequences in eubacterial genomes. Analyses of MgtC-like proteins phylogeny and mgtC-like chromosomal context support the hypothesis that mgtC has been acquired by horizontal gene transfer repeatedly throughout bacterial evolution. In addition, the phylogenetic analysis revealed the existence of a subgroup of proteins, that includes the S. typhimurium and M. tuberculosis MgtC proteins, as well as MgtC-related proteins from other pathogens that are able to survive in macrophages, B. melitensis and Y. pestis. We propose that MgtC has a similar function in all these distantly related pathogens, most likely providing the ability to grow in a low Mg2+ environment.

Amino Acid Sequence↗

Systematic review on genomic insights into antimicrobial resistance in ESKAPE pathogens.

BACKGROUND: Antimicrobial resistance (AMR) is a major global public health threat. ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pose a major threat owing to resistance to last-line antibiotics. Genomic surveillance is crucial to understanding global and regional antimicrobial resistance genes (ARGs) in AMR transmission. AIM: This systematic review synthesised global genomic evidence to identify global and region-specific ARGs distribution among ESKAPE pathogens. METHODS: Following PRISMA guidelines, studies published January 2019 to December 2024 were identified from PubMed, Google Scholar, and Web of Science. Eligible studies reported genomic characteristics and resistance patterns of one or more ESKAPE pathogens from any source. RESULTS: Seventy-seven studies were included, with most originating from Asia, followed by Europe and Africa. Clinical isolates predominated K. pneumoniae was the most frequently investigated pathogen, followed by S. aureus, P. aeruginosa, and A. baumannii. The most reported resistance genes were blaCTX-M, blaNDM, and blaSHV. Distinct regional patterns of antimicrobial resistance gene (ARG) distribution were observed, with tetracycline and quinolone resistance genes prevailing in Africa and South America, and blaOXA variants dominating in Asia and Europe. Region-specific ARG patterns were identified through descriptive synthesis and comparative analysis of study-reported frequencies. CONCLUSION: This review provides a synthesised global map of ARG distribution in ESKAPE pathogens, highlighting surveillance gaps in underrepresented regions and non-clinical settings. Addressing these gaps will support targeted genomic surveillance and stewardship programmes. WHAT THIS STUDY ADDS: This study contributes to the body of knowledge by mapping global and regional antimicrobial resistance gene patterns in ESKAPE pathogens, identifying key surveillance gaps and informing targeted AMR monitoring and stewardship strategies.

ESKAPE pathogens↗

Identification of genomic differences between Escherichia coli strains pathogenic for poultry and E. coli K-12 MG1655 using suppression subtractive hybridization analysis.

Diseases of poultry caused by Escherichia coli result in significant economic loss every year. Specific virulence factors associated with E. coli strains pathogenic for poultry have been identified, but it is likely that others remain to be identified. To identify unique DNA fragments associated with avian strains we used suppression subtractive hybridization. The genome of E. coli K-12 strain MG1655 was subtracted from the genomes of two avian E. coli strains resulting in the identification of 62 fragments specific to the two avian strains. Sequence homology analysis was done and four types of fragments were identified: plasmid sequences, phage sequences, sequences with known function and sequences without any currently known function. Two E. coli collections, a reference collection of diverse strains (ECOR) and a collection of 41 avian isolates, were screened for the presence of 25 of the 62 fragments. We identified nine fragments present in significantly more of the avian strains than of the ECOR strains. Five fragments were in significantly more of the ECOR strains than the avian strains. These results suggested that the nine fragments could play a role in the pathogenesis of E. coli as it relates to diseases of poultry.

Animals↗

Genome structure of spirochetes.

The genome structures of several pathogenic spirochetes have recently been determined. The genomes of Borrelia species consist of a linear chromosome of approximately one million base pairs (Mb) and various linear and circular plasmids. Analysis of restriction fragment length polymorphisms and 16S ribosomal RNA sequence data indicate the division of Borrelia burgdorferi into at least three distinct genetic groups. Leptospira interrogans has a circular chromosome 5 Mb in size and a 0.35 Mb extrachromosomal element. Repetitive sequence elements similar to insertion sequences have been identified in the Leptospira interrogans genome. The chromosome of Treponema pallidum subsp. pallidum is circular and has a size of approximately one Mb. Genetic studies conducted to date indicate that B. burgdorferi and L. interrogans have a high degree of genetic diversity, whereas remarkably few genetic differences have been observed among the pathogenic Treponema. Knowledge of the genomic structure of these organisms will serve as a basis for future genetic studies.

Borrelia burgdorferi Group↗