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PubMed2026

Whole-genome sequencing links a Salmonella Newport ST164 outbreak on Fernando de Noronha to prior circulation in the Brazilian poultry supply chain.

Foodborne outbreaks at geographically isolated tourist destinations pose distinctive One Health challenges, combining limited local surveillance capacity, complex intercontinental supply chains, and high visitor turnover. In May 2021, a diarrheal outbreak linked to a gastronomic festival in Fernando de Noronha, that is a remote UNESCO World Heritage island off northeastern Brazil, was attributed to Salmonella enterica serovar Newport ST164. We applied an integrated genomic approach and epidemiological investigation to propose a transmission chain contextualizing and refining case definition of the S. Newport epidemic clone within national and international diversity. Whole-genome sequencing (WGS), SNP-based phylogenomic, pangenome analysis, Salmonella pathogenicity island (SPI) profiling, and resistome characterization was performed on 17 epidemiologically attributed outbreak isolates and 68 contextual genomes from Brazil, France, the United Kingdom, and the United States. The SNP analysis identified a 13 genome clonal core with less than 20 different SNPs demonstrating the possible connection between 9 patient isolates, 2 food isolates, and 2 food handler isolates, consistent with the involvement of colonised kitchen staff in cross-contamination of the ready-to-eat mussel dish. Three poultry isolates in 2020 from a mainland producer, ∼2180 km from Fernando de Noronha, differed only 13 to 17 Core-SNPs from the outbreak core, suggesting prior lineage circulation in the supply chain. Pangenome analysis also supports this evidence revealing near-complete genomic overlap of 4544 shared genes within the 5745 gene clusters (99.9%) between outbreak and non-outbreak backgrounds that mostly differentiate by a defense/prophage-associated accessory module. The resistome comprised intrinsic efflux determinants without acquired resistance and showed 35.3% of intermediate ciprofloxacin susceptibility. This One Health based study provides a WGS genomic reconstruction of a S. Newport ST164 outbreak at a remote tourist island, supporting the possibility of circulation from poultry-associated mainland reservoirs and findings consistent with cross-contamination at a gastronomic seafood festival.

Brazil↗
PubMed2003

Two different thymidylate kinase gene homologues, including one that has catalytic activity, are encoded in the onion yellows phytoplasma genome.

Thymidylate kinase (TMK) catalyses the phosphorylation of dTMP to form dTDP in both the de novo and salvage pathways of dTTP synthesis in both prokaryotes and eukaryotes. Two homologues of bacterial thymidylate kinase genes were identified in a genomic library of the onion yellows (OY) phytoplasma, a plant pathogen that inhabits both plant phloem and the organs of insects. Southern blotting analysis suggested that the OY genome contained one copy of the tmk-b gene and multiple copies of the tmk-a gene. Sequencing of PCR products generated by amplification of tmk-a enabled identification of three other copies of tmk-a, although the ORF in each of these was interrupted by point mutations. The proteins, TMK-a and TMK-b, encoded by the two intact genes contained conserved motifs for catalytic activity. Both proteins were overexpressed as fusion proteins with a polyhistidine tag in Escherichia coli and purified, and TMK-b was shown to have thymidylate kinase activity. This is believed to be the first report of the catalytic activity of a phytoplasmal protein, and the OY phytoplasma is the first bacterial species to be found to have two intact homologues of tmk in its genome.

Acholeplasmataceae↗
PubMed2002

[Brucella at the dawn of the third milenium: genomic organization and pathogenesis].

Bacteria of the genus Brucella, responsible for brucellosis, are pathogenic for animals and occasionally for humans. The cost of this widespread zoonotic infection is still very high for the community. Over the last few years, there have been advances in two main domains. First, the Brucella genome has been shown to be complex, with two circular chromosomes. Second, recent data on the virulence of Brucella suggest common mechanisms shared with plant pathogens and endosymbionts of the alpha-proteobacteria. Understanding virulence will have practical repercussions in the realms of vaccine development and, perhaps, development of new antibiotics. Two complete Brucella genome sequences are now available and will be a gold mine of information to guide future research.

Animals↗
PubMed2005

Antigenome technology: a novel approach for the selection of bacterial vaccine candidate antigens.

A novel approach for the identification of protein antigens from bacterial pathogens was previously developed in our laboratory that combines the advantages of full genome coverage and serological antigen identification. We have applied this technology to several bacterial pathogens of the genera Staphylococcus and Streptococcus and have, as a result, defined the "antigenome" of these pathogens. This catalogue defines the most relevant antigenic proteins that are targeted by the human immune system, including their antibody binding sites. The antigenome technology offers an integrated approach for antigen validation in order to select the most promising candidates for the development of subunit vaccines against the targeted bacterial diseases. Using this technology, novel protective antigens were discovered from several important human pathogens.

Animals↗
PubMed2006

In vivo dissection of the Helicobacter pylori Fur regulatory circuit by genome-wide location analysis.

Iron homeostasis is particularly important in pathogenic bacteria, which need to compete with the host for this essential cofactor. In Helicobacter pylori, a causative agent of several gastric pathologies, iron uptake and storage genes are regulated at the transcriptional level by the ferric uptake regulator Fur. The regulatory circuit of Fur has recently come under focus because of an intimate interlink with a broader regulatory network governing metal homeostasis, acidic response, and virulence. To dissect the Fur regulatory circuit and identify in vivo targets of regulation, we developed a genome-wide location analysis protocol which allowed the identification of 200 genomic loci bound by Fur as well as the investigation of the binding efficiency of the protein to these loci in response to iron. Comparative analysis with transcriptomes of wild-type and fur deletion mutant strains allowed the distinction between targets associated with Fur regulation and genes indirectly influenced by the fur mutation. The Fur regulon includes 59 genes, 25 of which appear to be positively regulated. A case study conducted by primer extension analysis of two oppositely regulated genes, hpn2 and flaB, suggests that negative regulation as well as positive regulation occurs at the transcriptional level. Furthermore, the results revealed the existence of 13 Fur targeted loci within polycistronic operons, which were associated with transcript deregulation in the fur mutant strain. This study provides a systematic insight of Fur regulation at the genome-wide level in H. pylori and points to regulatory functions extending beyond the classical Fur repression paradigm.

Bacterial Proteins↗
PubMed2005

Comparative analyses of fundamental differences in membrane transport capabilities in prokaryotes and eukaryotes.

Whole-genome transporter analyses have been conducted on 141 organisms whose complete genome sequences are available. For each organism, the complete set of membrane transport systems was identified with predicted functions, and classified into protein families based on the transporter classification system. Organisms with larger genome sizes generally possessed a relatively greater number of transport systems. In prokaryotes and unicellular eukaryotes, the significant factor in the increase in transporter content with genome size was a greater diversity of transporter types. In contrast, in multicellular eukaryotes, greater number of paralogs in specific transporter families was the more important factor in the increase in transporter content with genome size. Both eukaryotic and prokaryotic intracellular pathogens and endosymbionts exhibited markedly limited transport capabilities. Hierarchical clustering of phylogenetic profiles of transporter families, derived from the presence or absence of a certain transporter family, showed that clustering patterns of organisms were correlated to both their evolutionary history and their overall physiology and lifestyles.

Biological Transport↗
PubMed2002

Novel antibacterials: a genomics approach to drug discovery.

The appearance of antibiotic resistant pathogens, including vancomycin resistant Staphylococcus aureus, in the clinic has necessitated the development of new antibiotics. The golden age of antibiotic discovery, in which potent selective compounds were readily extracted from natural product extracts is over and novel approaches need to be implemented to cover the therapeutic shortfall. The generation of huge quantities of bacterial sequence data has allowed the identification of all the possible targets for therapeutic intervention and allowed the development of screens to identify inhibitors. Here, we described a number of target classes in which genomics has contributed to its identification. As a result of analyzing sequence data, all of the tRNA synthetases and all of the two-component signal transduction systems were readily isolated; which would not have been easily identified if whole genome sequences were not available. Fatty acid biosynthesis is a known antibacterial target, but genomics showed which genes in that pathway had the appropriate spectrum to be considered as therapeutic targets. Genes of unknown function may seem untractable targets, but if those that are broad spectrum and essential are identified, it becomes valuable to invest time and effort to determine their cellular role. In addition, we discuss the role of genomics in developing technologies that assist in the discovery of new antibiotics including microarray gridding technology. Genomics can also increase the chemical diversity against which the novel targets can be screened.

Anti-Bacterial Agents↗
PubMed2005

Rapid differentiation of Mycobacterium bovis and Mycobacterium tuberculosis based on a 12.7-kb fragment by a single tube multiplex-PCR.

The aim of this work was the design and validation of a rapid and easy single tube multiplex-PCR (m-PCR) assay for the unequivocal differential detection of Mycobacterium bovis and Mycobacterium tuberculosis. Oligonucleotide primers were based on the uninterrupted 229-bp sequence in the M. bovis genome and a unique 12.7-kb insertion sequence from the M. tuberculosis genome, which is responsible for species-specific genomic polymorphism between these two closely related pathogens. The m-PCR assay was optimized and validated using 22 M. bovis and 36 M. tuberculosis clinical strains isolated from diverse host species and 9 other non-tuberculous mycobacterial (NTM) strains. The designed primers invariably amplified a unique 168-bp (M. bovis-specific) and 337-bp (M. tuberculosis-specific) amplicon from M. bovis and M. tuberculosis strains, respectively. The accuracy of the assay, in terms of specificity, was 100%, as none of the NTM strains tested revealed any amplification product. As little as 20 pg of genomic DNA could be detected, justifying the sensitivity of the method. The m-PCR assay is an extremely useful, simple, reliable and rapid method for routine differential identification of cultures of M. bovis and M. tuberculosis. This m-PCR may be a valuable diagnostic tool in areas of endemicity, where bovine and human tuberculosis coexist, and the distinction of M. bovis from M. tuberculosis is required for monitoring the spread of M. bovis to humans.

Animals↗
PubMed2025

Strain-level differences in Gardnerella urinary tract persistence and pathogenesis are consistent with comparative phylogenomic analyses.

BACKGROUND: Gardnerella is a genus of gram variable anaerobic bacteria that is commonly present in the female urogenital tract, especially during bacterial vaginosis (BV). BV is linked with increased risk of urinary tract infections (UTI) and Gardnerella has been frequently detected in urine collected directly from the bladder. Understanding the contribution of Gardnerella to urogenital pathogenesis has been complicated by its genetic heterogeneity and a shortage of data from in vivo models. Recently, a clinical isolate of Gardnerella displayed covert pathogenesis in a mouse urinary tract inoculation model, triggering urothelial exfoliation and promoting UTI by uropathogenic E. coli. Data from clinical studies suggests differential association of Gardnerella phylogenetic clades with BV or urogenital infections. In vitro data has demonstrated heterogeneity in the presence and expression of putative virulence determinants between Gardnerella strains. This study was designed to compare diverse Gardnerella strains in vivo to identify genomic variation associated with urinary tract persistence and pathogenesis. METHODS: Eighteen Gardnerella clinical isolates from each of the four main phylogenetic clades were individually inoculated transurethrally into female C57BL/6 mice. Bacteriuria was monitored by quantitative culturing of Gardnerella in urine. Pathologic features were assessed by immunofluorescent and histological staining of bladder tissues. Pan-genome phylogenetic analyses were performed on the 18 Gardnerella isolates used for mouse infections to identify accessory genes that were associated with observable in vivo phenotypes, including long and short-term persistence, urothelial exfoliation and bladder edema. Genes that were significantly associated to phenotype were then matched against a pangenome analysis of 291 publicly available Gardnerella genomes to determine the conservation of these putative colonization and virulence factors across the genus. RESULTS: Gardnerella strains displayed clear differences in persistence and pathogenesis in the mouse bladder that were congruent with phylogeny. Clade 2 strains were more persistent in the urinary tract whereas strains from the other three clades either caused transient bacteriuria or were undetectable. Strains from clade 2 and 4 induced urothelial exfoliation while edema was triggered by strains from clades 2, 3 and 4. Pangenome analyses revealed 45 genes that were associated with in vivo persistence and pathogenicity. Among the wider 291 publicly available genomes, clade 2 strains encoded more of the genes associated with bacteriuria phenotypes compared to strains in the other three clades. Exfoliation-associated genes were present in most clade 4 strains. Clade 3 strains lack most of the in vivo-associated genes, whereas clade 1 strains were more heterogenous. CONCLUSIONS: This study provides in vivo evidence for differential urinary tract colonization and pathogenesis by strains from different clades/species within the genus Gardnerella and identifies new putative persistence and virulence factors. Utilizing the in vivo data from tested strains, pangenome analyses predicts that clade 2 Gardnerella are the most likely to persist in the urinary tract and that clades 2 and 4 have the highest uropathogenic potential. These findings inform future targeted screening and treatment approaches aimed at limiting harmful Gardnerella urinary tract exposures.

Journal Article↗
PubMed2026

Molecular DNA enrichment methods for parasite genomic sequencing in clinical samples: a systematic review.

Parasitic diseases such as malaria, Chagas disease, leishmaniases, and helminthiases are major causes of sickness and death in low- and middle-income countries. The high genetic diversity of these pathogens affects virulence, immune evasion, and diagnostic accuracy. Although Whole Genome Sequencing (WGS) is a powerful tool for tracking genetic variants and drug resistance, low parasitemia and the predominance of host DNA limit its application to clinical samples. This study systematically reviewed molecular strategies to improve the recovery of parasite DNA from clinical samples, following PRISMA 2020 guidelines and registered in PROSPERO. Searches of PubMed, Scopus, Web of Science, and LILACS up to December 2025 identified 20 eligible studies, most of which focused on protozoa, particularly Plasmodium spp. The main approaches included hybridization capture, selective whole-genome amplification, host DNA depletion, and in silico enrichment via adaptive sampling. Overall, no single method is suitable for all parasites analyzed; the optimal approach depends on the pathogen, sample type, and research objective. The review emphasizes that parasite DNA enrichment is essential for enabling WGS in clinical settings, underscoring the need for protocol standardization and cost-effectiveness analyses to support public health genomic surveillance.

Adaptive sampling↗
PubMed2003

The yersiniae--a model genus to study the rapid evolution of bacterial pathogens.

Yersinia pestis, the causative agent of plague, seems to have evolved from a gastrointestinal pathogen, Yersinia pseudotuberculosis, in just 1,500-20,000 years--an 'eye blink' in evolutionary time. The third pathogenic Yersinia, Yersinia enterocolitica, also causes gastroenteritis but is distantly related to Y. pestis and Y. pseudotuberculosis. Why do the two closely related species cause remarkably different diseases, whereas the distantly related enteropathogens cause similar symptoms? The recent availability of whole-genome sequences and information on the biology of the pathogenic yersiniae have shed light on this paradox, and revealed ways in which new, highly virulent pathogens can evolve.

Animals↗
PubMed2005

Extensive DNA inversions in the B. fragilis genome control variable gene expression.

The obligately anaerobic bacterium Bacteroides fragilis, an opportunistic pathogen and inhabitant of the normal human colonic microbiota, exhibits considerable within-strain phase and antigenic variation of surface components. The complete genome sequence has revealed an unusual breadth (in number and in effect) of DNA inversion events that potentially control expression of many different components, including surface and secreted components, regulatory molecules, and restriction-modification proteins. Invertible promoters of two different types (12 group 1 and 11 group 2) were identified. One group has inversion crossover (fix) sites similar to the hix sites of Salmonella typhimurium. There are also four independent intergenic shufflons that potentially alter the expression and function of varied genes. The composition of the 10 different polysaccharide biosynthesis gene clusters identified (7 with associated invertible promoters) suggests a mechanism of synthesis similar to the O-antigen capsules of Escherichia coli.

Bacterial Outer Membrane Proteins↗
PubMed2026

Complete genome sequence of an antibiotic-resistant and virulent Escherichia marmotae isolate recovered from a urinary tract infection.

OBJECTIVES: We aimed at analyzing the whole genome of the antibiotic-resistant Escherichia marmotae isolate 23-MO01035-0, which was obtained from a urinary tract infection of a male patient in Germany. The study focused on the characterization of mobile genetic elements and genetic factors that contribute to antibiotic resistance and pathogenicity. METHODS: Phenotypic antimicrobial susceptibility testing was performed and genomic DNA was sequenced using Illumina NextSeq (2 × 151 bp) and a MinION Mk1C device followed by de novo hybrid assembly using Unicycler v0.4.8. Resistance genes, virulence factors, plasmids, and mobile elements were identified with the bakcharak pipeline and PathogenFinder. RESULTS: The isolate belonged to sequence type ST133 and the 5,041,084 bp whole genome, consisting of one chromosome and five plasmids with an average GC content of 50.4%, revealed resistance genes for various antibiotic classes on an IncFII plasmid that had not yet been described. The isolate was predicted to be a potential human pathogen due to the presence of multiple virulence genes. CONCLUSION: Here, we report one of the first detailed genomic characterization of an antibiotic-resistant and virulent E. marmotae isolate from Germany. Considering that this bacterium was isolated from the urinary tract and possibly belonged to the faecal microbiota of the patient at that time, E. marmotae might contribute to the spread of antibiotic resistance in humans. This underscores the importance of genomic surveillance of E. marmotae, which causes human infections, but may be misidentified as E. coli.

Escherichia marmotae↗
PubMed2003

Position-based scanning for comparative genomics and identification of genetic islands in Haemophilus influenzae type b.

Bacteria exhibit extensive genetic heterogeneity within species. In many cases, these differences account for virulence properties unique to specific strains. Several such loci have been discovered in the genome of the type b serotype of Haemophilus influenzae, a human pathogen able to cause meningitis, pneumonia, and septicemia. Here we report application of a PCR-based scanning procedure to compare the genome of a virulent type b (Hib) strain with that of the laboratory-passaged Rd KW20 strain for which a complete genome sequence is available. We have identified seven DNA segments or H. influenzae genetic islands (HiGIs) present in the type b genome and absent from the Rd genome. These segments vary in size and content and show signs of horizontal gene transfer in that their percent G+C content differs from that of the rest of the H. influenzae genome, they contain genes similar to those found on phages or other mobile elements, or they are flanked by DNA repeats. Several of these loci represent potential pathogenicity islands, because they contain genes likely to mediate interactions with the host. These newly identified genetic islands provide areas of investigation into both the evolution and pathogenesis of H. influenzae. In addition, the genome scanning approach developed to identify these islands provides a rapid means to compare the genomes of phenotypically diverse bacterial strains once the genome sequence of one representative strain has been determined.

Amino Acid Sequence↗
PubMed2004

Comparative genomics identified two conserved DNA modules in a corynebacterial plasmid family present in clinical isolates of the opportunistic human pathogen Corynebacterium jeikeium.

Investigation of 62 clinical isolates of the opportunistic human pathogen Corynebacterium jeikeium revealed that 17 possessed plasmids ranging in size from 7.6 to 14.9 kb. The plasmids formed four groups on DNA restriction analysis. The complete nucleotide sequence of a representative from each group (pK43, pK64, pCJ84, and pB85766) was subsequently determined. Additionally, two plasmids (pCo455 and pCo420) were shown to be derivatives of pK43 and pK64 carrying insertion sequences of the IS3 family. Comparative genomics identified a conserved plasmid backbone consisting of two distinct DNA modules. Conserved motifs in the parAB-repA module indicated that the sequenced plasmids from C. jeikeium are new members of the pNG2 family. Recombinant derivatives of pK43 were shown to replicate in the soil bacterium Corynebacterium glutamicum and in the human pathogen Corynebacterium diphtheriae. The second plasmid module most likely encodes a novel type of DNA invertase. The respective gene is flanked by highly conserved 112-bp inverted repeats. All plasmids are 'loaded' with a characteristic set of genes encoding products of unknown function. Plasmids indistinguishable from pK43 by DNA restriction analysis were identified in different C. jeikeium strains, which revealed 16S-23S rDNA spacer length polymorphisms and specific antibiotic susceptibility profiles, implying a wide dissemination of the plasmid in clinical isolates of C. jeikeium.

Amino Acid Sequence↗
PubMed2025

Estimating Re and overdispersion in secondary cases from the size of identical sequence clusters of SARS-CoV-2.

The wealth of genomic data that was generated during the COVID-19 pandemic provides an exceptional opportunity to obtain information on the transmission of SARS-CoV-2. Specifically, there is great interest to better understand how the effective reproduction number [Formula: see text] and the overdispersion of secondary cases, which can be quantified by the negative binomial dispersion parameter k, changed over time and across regions and viral variants. The aim of our study was to develop a Bayesian framework to infer [Formula: see text] and k from viral sequence data. First, we developed a mathematical model for the distribution of the size of identical sequence clusters, in which we integrated viral transmission, the mutation rate of the virus, and incomplete case-detection. Second, we implemented this model within a Bayesian inference framework, allowing the estimation of [Formula: see text] and k from genomic data only. We validated this model in a simulation study. Third, we identified clusters of identical sequences in all SARS-CoV-2 sequences in 2021 from Switzerland, Denmark, and Germany that were available on GISAID. We obtained monthly estimates of the posterior distribution of [Formula: see text] and k, with the resulting [Formula: see text] estimates slightly lower than estimates obtained by other methods, and k comparable with previous results. We found comparatively higher estimates of k in Denmark which suggests less opportunities for superspreading and more controlled transmission compared to the other countries in 2021. Our model included an estimation of the case detection and sampling probability, but the estimates obtained had large uncertainty, reflecting the difficulty of estimating these parameters simultaneously. Our study presents a novel method to infer information on the transmission of infectious diseases and its heterogeneity using genomic data. With increasing availability of sequences of pathogens in the future, we expect that our method has the potential to provide new insights into the transmission and the overdispersion in secondary cases of other pathogens.

COVID-19↗
PubMed2003

Effects of GC content and mutational pressure on the lengths of exons and coding sequences.

It has been hypothesized that the length of an exon tends to increase with the GC content because stop codons are AT-rich and should occur less frequently in GC-rich exons. This prediction assumes that mutation pressure plays a significant role in the occurrence and distribution of stop codons. However, the prediction is applicable not to all exons, but only to the last coding exon of a gene and to single-exon CDS sequences. We classified exons in multiexon genes in eight eukaryotic species into three groups-the first exon, the internal, and the last exon-and computed the Spearman correlation between the exon length and the percentage GC (%GC) for each of the three groups. In only five of the species studied is the correlation for the last coding exon greater than that for the first or internal exons. For the single-exon CDS sequences, the correlation between CDS length and %GC is mostly negative. Thus, eukaryotic genomes do not support the predicted relationship between exon length and %GC. In prokaryotic genomes, CDS length and %GC are positively correlated in each of the 68 completely sequenced prokaryotic genomes in GenBank with genomic GC contents varying from 25 to 68%, except for the wall-less Mycoplasma genitalium and the syphilis pathogen Treponema pallidum. Moreover, the average CDS length and the genomic GC content are also positively correlated. After correcting for genome size, the partial correlation between the average CDS length and the genomic GC content is 0.3217 ( p < 0.025).

Animals↗
PubMed2006

Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients.

In many human infections, hosts and pathogens coexist for years or decades. Important examples include HIV, herpes viruses, tuberculosis, leprosy, and malaria. With the exception of intensively studied viral infections such as HIV/AIDs, little is known about the extent to which the clonal expansion that occurs during long-term infection by pathogens involves important genetic adaptations. We report here a detailed, whole-genome analysis of one such infection, that of a cystic fibrosis (CF) patient by the opportunistic bacterial pathogen Pseudomonas aeruginosa. The bacteria underwent numerous genetic adaptations during 8 years of infection, as evidenced by a positive-selection signal across the genome and an overwhelming signal in specific genes, several of which are mutated during the course of most CF infections. Of particular interest is our finding that virulence factors that are required for the initiation of acute infections are often selected against during chronic infections. It is apparent that the genotypes of the P. aeruginosa strains present in advanced CF infections differ systematically from those of "wild-type" P. aeruginosa and that these differences may offer new opportunities for treatment of this chronic disease.

Adaptation, Physiological↗