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Pathogens
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Bacterial Pathogenomics: From Technology to Application
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Bacterial Pathogenomics: From Technology to Application

A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: closed (31 January 2014) | Viewed by 126331

Special Issue Editor

Dr. Anthony Underwood

E-Mail Website
Guest Editor
Bioinformatics Group | Applied Laboratory and Bio- Informatics Unit, Microbiology Services, Colindale, Public Health England 61 Colindale Avenue, London NW9 5EQ, UK
Interests: pathogen genomics; phylogenomics; virulence; microbiology; public health

Special Issue Information

Dear Colleagues,

The first bacterial genome required a large team and many person years to complete. With current high throughput massively-parallel sequencing technologies it is possible to generate a nearly complete bacterial genome in just a few days. This major revolution opens up huge opportunities, particularly in the ability to compare the whole genomes of many bacterial isolates. This might include trying to answer basic biological questions by looking at genome wide associations and attempting to link genetic features to phenotypic traits. However the questions being asked can also be much more applied, such as using whole genome phylogenies to look for evidence of transmission within a community or hospital or find the source of a disease outbreak.

In this special issue, we invite investigators to submit manuscripts that cover this broad topic. These can include everything from novel uses of current sequencing technology to investigate bacterial genomics, to cutting edge applications of whole genome sequencing to 'real world' scenarios.

We look forward to your contribution.

Dr. Anthony Underwood
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (15 papers)

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Research

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706 KiB  
Article
Transcriptional Profiling of a Cross-Protective Salmonella enterica serovar Typhimurium UK-1 dam Mutant Identifies a Set of Genes More Transcriptionally Active Compared to Wild-Type, and Stably Transcribed across Biologically Relevant Microenvironments
by Claire B. Miller, Sebastian Aguilar Pierlé, Kelly A. Brayton, Jennine N. Ochoa, Devendra H. Shah and Kevin K. Lahmers
Pathogens 2014, 3(2), 417-436; https://doi.org/10.3390/pathogens3020417 - 09 May 2014
Cited by 3 | Viewed by 6188
Abstract
Vaccination with Salmonella enterica serovar Typhimurium lacking DNA adenine methyltransferase confers cross-protective immunity against multiple Salmonella serotypes. The mechanistic basis is thought to be associated with the de-repression of genes that are tightly regulated when transiting from one microenvironment to another. This de-repression [...] Read more.
Vaccination with Salmonella enterica serovar Typhimurium lacking DNA adenine methyltransferase confers cross-protective immunity against multiple Salmonella serotypes. The mechanistic basis is thought to be associated with the de-repression of genes that are tightly regulated when transiting from one microenvironment to another. This de-repression provides a potential means for the production of a more highly expressed and stable antigenic repertoire capable of inducing cross-protective immune responses. To identify genes encoding proteins that may contribute to cross-protective immunity, we used a Salmonella Typhimurium DNA adenine methyltransferase mutant strain (UK-1 dam mutant) derived from the parental UK-1 strain, and assessed the transcriptional profile of the UK-1 dam mutant and UK-1 strain grown under conditions that simulate the intestinal or endosomal microenvironments encountered during the infective process. As expected, the transcriptional profile of the UK-1 dam mutant identified a set of genes more transcriptionally active when compared directly to UK-1, and stably transcribed in biologically relevant culture conditions. Further, 22% of these genes were more highly transcribed in comparison to two other clinically-relevant Salmonella serovars. The strategy employed here helps to identify potentially conserved proteins produced by the UK-1 dam mutant that stimulate and/or modulate the development of cross-protective immune responses toward multiple Salmonella serotypes. Full article
(This article belongs to the Special Issue Bacterial Pathogenomics: From Technology to Application)
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2958 KiB  
Article
Characterization of Antimicrobial Resistance Dissemination across Plasmid Communities Classified by Network Analysis
by Akifumi Yamashita, Tsuyoshi Sekizuka and Makoto Kuroda
Pathogens 2014, 3(2), 356-376; https://doi.org/10.3390/pathogens3020356 - 15 Apr 2014
Cited by 18 | Viewed by 8373
Abstract
The global clustering of gene families through network analysis has been demonstrated in whole genome, plasmid, and microbiome analyses. In this study, we carried out a plasmidome network analysis of all available complete bacterial plasmids to determine plasmid associations. A blastp clustering search [...] Read more.
The global clustering of gene families through network analysis has been demonstrated in whole genome, plasmid, and microbiome analyses. In this study, we carried out a plasmidome network analysis of all available complete bacterial plasmids to determine plasmid associations. A blastp clustering search at 100% aa identity cut-off and sharing at least one gene between plasmids, followed by a multilevel community network analysis revealed that a surprisingly large number of the plasmids were connected by one largest connected component (LCC), with dozens of community sub-groupings. The LCC consisted mainly of Bacilli and Gammaproteobacteria plasmids. Intriguingly, horizontal gene transfer (HGT) was noted between different phyla (i.e., Staphylococcus and Pasteurellaceae), suggesting that Pasteurellaceae can acquire antimicrobial resistance (AMR) genes from closely contacting Staphylococcus spp., which produce the external supplement of V-factor (NAD). Such community network analysis facilitate displaying possible recent HGTs like a class 1 integron, str and tet resistance markers between communities. Furthermore, the distribution of the Inc replicon type and AMR genes, such as the extended-spectrum ß-lactamase (ESBL) CTX-M or the carbapenemases KPC NDM-1, implies that such genes generally circulate within limited communities belonging to typical bacterial genera. Thus, plasmidome network analysis provides a remarkable discriminatory power for plasmid-related HGT and evolution. Full article
(This article belongs to the Special Issue Bacterial Pathogenomics: From Technology to Application)
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1283 KiB  
Article
Pseudomonas aeruginosa Genome Evolution in Patients and under the Hospital Environment
by Céline Lucchetti-Miganeh, David Redelberger, Gaël Chambonnier, François Rechenmann, Sylvie Elsen, Christophe Bordi, Katy Jeannot, Ina Attrée, Patrick Plésiat and Sophie De Bentzmann
Pathogens 2014, 3(2), 309-340; https://doi.org/10.3390/pathogens3020309 - 10 Apr 2014
Cited by 16 | Viewed by 8893
Abstract
Pseudomonas aeruginosa is a Gram-negative environmental species and an opportunistic microorganism, establishing itself in vulnerable patients, such as those with cystic fibrosis (CF) or those hospitalized in intensive care units (ICU). It has become a major cause of nosocomial infections worldwide and a [...] Read more.
Pseudomonas aeruginosa is a Gram-negative environmental species and an opportunistic microorganism, establishing itself in vulnerable patients, such as those with cystic fibrosis (CF) or those hospitalized in intensive care units (ICU). It has become a major cause of nosocomial infections worldwide and a serious threat to Public Health because of overuse and misuse of antibiotics that have selected highly resistant strains against which very few therapeutic options exist. Herein is illustrated the intraclonal evolution of the genome of sequential isolates collected in a single CF patient from the early phase of pulmonary colonization to the fatal outcome. We also examined at the whole genome scale a pair of genotypically-related strains made of a drug susceptible, environmental isolate recovered from an ICU sink and of its multidrug resistant counterpart found to infect an ICU patient. Multiple genetic changes accumulated in the CF isolates over the disease time course including SNPs, deletion events and reduction of whole genome size. The strain isolated from the ICU patient displayed an increase in the genome size of 4.8% with major genetic rearrangements as compared to the initial environmental strain. The annotated genomes are given in free access in an interactive web application WallGene designed to facilitate large-scale comparative analysis and thus allowing investigators to explore homologies and syntenies between P. aeruginosa strains, here PAO1 and the five clinical strains described. Full article
(This article belongs to the Special Issue Bacterial Pathogenomics: From Technology to Application)
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2436 KiB  
Article
Genome Sequencing of Xanthomonas vasicola Pathovar vasculorum Reveals Variation in Plasmids and Genes Encoding Lipopolysaccharide Synthesis, Type-IV Pilus and Type-III Secretion Effectors
by Arthur Wasukira, Max Coulter, Noorah Al-Sowayeh, Richard Thwaites, Konrad Paszkiewicz, Jerome Kubiriba, Julian Smith, Murray Grant and David J. Studholme
Pathogens 2014, 3(1), 211-237; https://doi.org/10.3390/pathogens3010211 - 18 Mar 2014
Cited by 20 | Viewed by 9010
Abstract
Xanthomonas vasicola pathovar vasculorum (Xvv) is the bacterial agent causing gumming disease in sugarcane. Here, we compare complete genome sequences for five isolates of Xvv originating from sugarcane and one from maize. This identified two distinct types of lipopolysaccharide synthesis gene [...] Read more.
Xanthomonas vasicola pathovar vasculorum (Xvv) is the bacterial agent causing gumming disease in sugarcane. Here, we compare complete genome sequences for five isolates of Xvv originating from sugarcane and one from maize. This identified two distinct types of lipopolysaccharide synthesis gene clusters among Xvv isolates: one is similar to that of Xanthomonas axonopodis pathovar citri (Xac) and is probably the ancestral type, while the other is similar to those of the sugarcane-inhabiting species, Xanthomonas sacchari. Four of six Xvv isolates harboured sequences similar to the Xac plasmid, pXAC47, and showed a distinct Type-IV pilus (T4P) sequence type, whereas the T4P locus of the other two isolates resembled that of the closely related banana pathogen, Xanthomonas campestris pathovar musacearum (Xcm). The Xvv isolate from maize has lost a gene encoding a homologue of the virulence effector, xopAF, which was present in all five of the sugarcane isolates, while xopL contained a premature stop codon in four out of six isolates. These findings shed new light on evolutionary events since the divergence of Xvv and Xcm, as well as further elucidating the relationships between the two closely related pathogens. Full article
(This article belongs to the Special Issue Bacterial Pathogenomics: From Technology to Application)
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532 KiB  
Article
Genomics-Based Exploration of Virulence Determinants and Host-Specific Adaptations of Pseudomonas syringae Strains Isolated from Grasses
by Alexey Dudnik and Robert Dudler
Pathogens 2014, 3(1), 121-148; https://doi.org/10.3390/pathogens3010121 - 28 Jan 2014
Cited by 12 | Viewed by 7957
Abstract
The Pseudomonas syringae species complex has recently been named the number one plant pathogen, due to its economic and environmental impacts, as well as for its role in scientific research. The bacterium has been repeatedly reported to cause outbreaks on bean, cucumber, stone [...] Read more.
The Pseudomonas syringae species complex has recently been named the number one plant pathogen, due to its economic and environmental impacts, as well as for its role in scientific research. The bacterium has been repeatedly reported to cause outbreaks on bean, cucumber, stone fruit, kiwi and olive tree, as well as on other crop and non-crop plants. It also serves as a model organism for research on the Type III secretion system (T3SS) and plant-pathogen interactions. While most of the current work on this pathogen is either carried out on one of three model strains found on dicot plants with completely sequenced genomes or on isolates obtained from recent outbreaks, not much is known about strains isolated from grasses (Poaceae). Here, we use comparative genomics in order to identify putative virulence-associated genes and other Poaceae-specific adaptations in several newly available genome sequences of strains isolated from grass species. All strains possess only a small number of known Type III effectors, therefore pointing to the importance of non-Type III secreted virulence factors. The implications of this finding are discussed. Full article
(This article belongs to the Special Issue Bacterial Pathogenomics: From Technology to Application)
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580 KiB  
Article
Live Genomics for Pathogen Monitoring in Public Health
by Giuseppe D'Auria, Maria Victoria Schneider and Andrés Moya
Pathogens 2014, 3(1), 93-108; https://doi.org/10.3390/pathogens3010093 - 21 Jan 2014
Cited by 4 | Viewed by 8839
Abstract
Whole genome analysis based on next generation sequencing (NGS) now represents an affordable framework in public health systems. Robust analytical pipelines of genomic data provides in short laps of time (hours) information about taxonomy, comparative genomics (pan-genome) and single polymorphisms profiles. Pathogenic organisms [...] Read more.
Whole genome analysis based on next generation sequencing (NGS) now represents an affordable framework in public health systems. Robust analytical pipelines of genomic data provides in short laps of time (hours) information about taxonomy, comparative genomics (pan-genome) and single polymorphisms profiles. Pathogenic organisms of interest can be tracked at the genomic level, allowing monitoring at one-time several variables including: epidemiology, pathogenicity, resistance to antibiotics, virulence, persistence factors, mobile elements and adaptation features. Such information can be obtained not only at large spectra, but also at the “local” level, such as in the event of a recurrent or emergency outbreak. This paper reviews the state of the art in infection diagnostics in the context of modern NGS methodologies. We describe how actuation protocols in a public health environment will benefit from a “streaming approach” (pipeline). Such pipeline would NGS data quality assessment, data mining for comparative analysis, searching differential genetic features, such as virulence, resistance persistence factors and mutation profiles (SNPs and InDels) and formatted “comprehensible” results. Such analytical protocols will enable a quick response to the needs of locally circumscribed outbreaks, providing information on the causes of resistance and genetic tracking elements for rapid detection, and monitoring actuations for present and future occurrences. Full article
(This article belongs to the Special Issue Bacterial Pathogenomics: From Technology to Application)
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1273 KiB  
Article
Genetic Diversity of Tick-Borne Rickettsial Pathogens; Insights Gained from Distant Strains
by Sebastián Aguilar Pierlé, Ivan Imaz-Rosshandler, Ammielle Akim Kerudin, Jacqueline Sambono, Ala Lew-Tabor, Peter Rolls, Claudia Rangel-Escareño and Kelly A. Brayton
Pathogens 2014, 3(1), 57-72; https://doi.org/10.3390/pathogens3010057 - 14 Jan 2014
Cited by 13 | Viewed by 7570
Abstract
The ability to capture genetic variation with unprecedented resolution improves our understanding of bacterial populations and their ability to cause disease. The goal of the pathogenomics era is to define genetic diversity that results in disease. Despite the economic losses caused by vector-borne [...] Read more.
The ability to capture genetic variation with unprecedented resolution improves our understanding of bacterial populations and their ability to cause disease. The goal of the pathogenomics era is to define genetic diversity that results in disease. Despite the economic losses caused by vector-borne bacteria in the Order Rickettsiales, little is known about the genetic variants responsible for observed phenotypes. The tick-transmitted rickettsial pathogen Anaplasma marginale infects cattle in tropical and subtropical regions worldwide, including Australia. Genomic analysis of North American A. marginale strains reveals a closed core genome defined by high levels of Single Nucleotide Polymorphisms (SNPs). Here we report the first genome sequences and comparative analysis for Australian strains that differ in virulence and transmissibility. A list of genetic differences that segregate with phenotype was evaluated for the ability to distinguish the attenuated strain from virulent field strains. Phylogenetic analyses of the Australian strains revealed a marked evolutionary distance from all previously sequenced strains. SNP analysis showed a strikingly reduced genetic diversity between these strains, with the smallest number of SNPs detected between any two A. marginale strains. The low diversity between these phenotypically distinct bacteria presents a unique opportunity to identify the genetic determinants of virulence and transmission. Full article
(This article belongs to the Special Issue Bacterial Pathogenomics: From Technology to Application)
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2973 KiB  
Article
Comparative Genomics Identifies a Potential Marker of Human-Virulent Anaplasma phagocytophilum
by Basima Al-Khedery and Anthony F. Barbet
Pathogens 2014, 3(1), 25-35; https://doi.org/10.3390/pathogens3010025 - 09 Jan 2014
Cited by 12 | Viewed by 7963
Abstract
We have previously described a comparative genome analysis of nine strains of Anaplasma phagocytophilum that showed similarity between strains infecting humans and U.S. dogs and a more distant relationship with horse and ruminant strains. This suggested that it may be possible to distinguish [...] Read more.
We have previously described a comparative genome analysis of nine strains of Anaplasma phagocytophilum that showed similarity between strains infecting humans and U.S. dogs and a more distant relationship with horse and ruminant strains. This suggested that it may be possible to distinguish human-infective strains using simple DNA sequence-based diagnostic tests. This would be of epidemiologic significance in identifying and tracking the presence of virulent strains in tick vector populations. Further analysis identified a gene that was present in several strains, including U.S. Ap-variant 1 (ruminant), MRK (horse), and European sheep, but was deleted in strains infecting U.S. humans and dogs, suggesting that it could be a useful marker of human virulence. A simple PCR test was developed to identify the presence/absence of this gene. The PCR test discriminated A. phagocytophilum strains from clinically affected humans and U.S. dogs from the strains more distantly related in genome sequence. This warrants further testing of globally diverse A. phagocytophilum strains to examine world-wide conservation of this gene. Full article
(This article belongs to the Special Issue Bacterial Pathogenomics: From Technology to Application)
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266 KiB  
Article
Whole-Proteome Analysis of Twelve Species of Alphaproteobacteria Links Four Pathogens
by Yunyun Zhou, Douglas R. Call and Shira L. Broschat
Pathogens 2013, 2(4), 627-635; https://doi.org/10.3390/pathogens2040627 - 26 Nov 2013
Cited by 1 | Viewed by 5671
Abstract
Thousands of whole-genome and whole-proteome sequences have been made available through advances in sequencing technology, and sequences of millions more organisms will become available in the coming years. This wealth of genetic information will provide numerous opportunities to enhance our understanding of these [...] Read more.
Thousands of whole-genome and whole-proteome sequences have been made available through advances in sequencing technology, and sequences of millions more organisms will become available in the coming years. This wealth of genetic information will provide numerous opportunities to enhance our understanding of these organisms including a greater understanding of relationships among species. Researchers have used 16S rRNA and other gene sequences to study the evolutionary origins of bacteria, but these strategies do not provide insight into the sharing of genes among bacteria via horizontal transfer. In this work we use an open source software program called pClust to cluster proteins from the complete proteomes of twelve species of Alphaproteobacteria and generate a dendrogram from the resulting orthologous protein clusters. We compare the results with dendrograms constructed using the 16S rRNA gene and multiple sequence alignment of seven housekeeping genes. Analysis of the whole proteomes of these pathogens grouped Rickettsia typhi with three other animal pathogens whereas conventional sequence analysis failed to group these pathogens together. We conclude that whole-proteome analysis can give insight into relationships among species beyond their phylogeny, perhaps reflecting the effects of horizontal gene transfer and potentially providing insight into the functions of shared genes by means of shared phenotypes. Full article
(This article belongs to the Special Issue Bacterial Pathogenomics: From Technology to Application)
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1464 KiB  
Article
Comprehensive Analysis of Prokaryotes in Environmental Water Using DNA Microarray Analysis and Whole Genome Amplification
by Takeshi Akama, Akira Kawashima, Kazunari Tanigawa, Moyuru Hayashi, Yuko Ishido, Yuqian Luo, Akihisa Hata, Noboru Fujitani, Norihisa Ishii and Koichi Suzuki
Pathogens 2013, 2(4), 591-605; https://doi.org/10.3390/pathogens2040591 - 30 Oct 2013
Cited by 2 | Viewed by 5625
Abstract
The microflora in environmental water consists of a high density and diversity of bacterial species that form the foundation of the water ecosystem. Because the majority of these species cannot be cultured in vitro, a different approach is needed to identify prokaryotes [...] Read more.
The microflora in environmental water consists of a high density and diversity of bacterial species that form the foundation of the water ecosystem. Because the majority of these species cannot be cultured in vitro, a different approach is needed to identify prokaryotes in environmental water. A novel DNA microarray was developed as a simplified detection protocol. Multiple DNA probes were designed against each of the 97,927 sequences in the DNA Data Bank of Japan and mounted on a glass chip in duplicate. Evaluation of the microarray was performed using the DNA extracted from one liter of environmental water samples collected from seven sites in Japan. The extracted DNA was uniformly amplified using whole genome amplification (WGA), labeled with Cy3-conjugated 16S rRNA specific primers and hybridized to the microarray. The microarray successfully identified soil bacteria and environment-specific bacteria clusters. The DNA microarray described herein can be a useful tool in evaluating the diversity of prokaryotes and assessing environmental changes such as global warming. Full article
(This article belongs to the Special Issue Bacterial Pathogenomics: From Technology to Application)
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896 KiB  
Article
An Emerging Tick-Borne Disease of Humans Is Caused by a Subset of Strains with Conserved Genome Structure
by Anthony F. Barbet, Basima Al-Khedery, Snorre Stuen, Erik G. Granquist, Roderick F. Felsheim and Ulrike G. Munderloh
Pathogens 2013, 2(3), 544-555; https://doi.org/10.3390/pathogens2030544 - 10 Sep 2013
Cited by 34 | Viewed by 8457
Abstract
The prevalence of tick-borne diseases is increasing worldwide. One such emerging disease is human anaplasmosis. The causative organism, Anaplasma phagocytophilum, is known to infect multiple animal species and cause human fatalities in the U.S., Europe and Asia. Although long known to infect [...] Read more.
The prevalence of tick-borne diseases is increasing worldwide. One such emerging disease is human anaplasmosis. The causative organism, Anaplasma phagocytophilum, is known to infect multiple animal species and cause human fatalities in the U.S., Europe and Asia. Although long known to infect ruminants, it is unclear why there are increasing numbers of human infections. We analyzed the genome sequences of strains infecting humans, animals and ticks from diverse geographic locations. Despite extensive variability amongst these strains, those infecting humans had conserved genome structure including the pfam01617 superfamily that encodes the major, neutralization-sensitive, surface antigen. These data provide potential targets to identify human-infective strains and have significance for understanding the selective pressures that lead to emergence of disease in new species. Full article
(This article belongs to the Special Issue Bacterial Pathogenomics: From Technology to Application)
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Review

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2226 KiB  
Review
Leptospiral Pathogenomics
by Jason S. Lehmann, Michael A. Matthias, Joseph M. Vinetz and Derrick E. Fouts
Pathogens 2014, 3(2), 280-308; https://doi.org/10.3390/pathogens3020280 - 10 Apr 2014
Cited by 78 | Viewed by 14309
Abstract
Leptospirosis, caused by pathogenic spirochetes belonging to the genus Leptospira, is a zoonosis with important impacts on human and animal health worldwide. Research on the mechanisms of Leptospira pathogenesis has been hindered due to slow growth of infectious strains, poor transformability, and [...] Read more.
Leptospirosis, caused by pathogenic spirochetes belonging to the genus Leptospira, is a zoonosis with important impacts on human and animal health worldwide. Research on the mechanisms of Leptospira pathogenesis has been hindered due to slow growth of infectious strains, poor transformability, and a paucity of genetic tools. As a result of second generation sequencing technologies, there has been an acceleration of leptospiral genome sequencing efforts in the past decade, which has enabled a concomitant increase in functional genomics analyses of Leptospira pathogenesis. A pathogenomics approach, by coupling of pan-genomic analysis of multiple isolates with sequencing of experimentally attenuated highly pathogenic Leptospira, has resulted in the functional inference of virulence factors. The global Leptospira Genome Project supported by the U.S. National Institute of Allergy and Infectious Diseases to which key scientific contributions have been made from the international leptospirosis research community has provided a new roadmap for comprehensive studies of Leptospira and leptospirosis well into the future. This review describes functional genomics approaches to apply the data generated by the Leptospira Genome Project towards deepening our knowledge of virulence factors of Leptospira using the emerging discipline of pathogenomics. Full article
(This article belongs to the Special Issue Bacterial Pathogenomics: From Technology to Application)
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889 KiB  
Review
Genomic and Global Approaches to Unravelling How Hypermutable Sequences Influence Bacterial Pathogenesis
by Fadil A. Bidmos and Christopher D. Bayliss
Pathogens 2014, 3(1), 164-184; https://doi.org/10.3390/pathogens3010164 - 25 Feb 2014
Cited by 14 | Viewed by 7252
Abstract
Rapid adaptation to fluctuations in the host milieu contributes to the host persistence and virulence of bacterial pathogens. Adaptation is frequently mediated by hypermutable sequences in bacterial pathogens. Early bacterial genomic studies identified the multiplicity and virulence-associated functions of these hypermutable sequences. Thus, [...] Read more.
Rapid adaptation to fluctuations in the host milieu contributes to the host persistence and virulence of bacterial pathogens. Adaptation is frequently mediated by hypermutable sequences in bacterial pathogens. Early bacterial genomic studies identified the multiplicity and virulence-associated functions of these hypermutable sequences. Thus, simple sequence repeat tracts (SSRs) and site-specific recombination were found to control capsular type, lipopolysaccharide structure, pilin diversity and the expression of outer membrane proteins. We review how the population diversity inherent in the SSR-mediated mechanism of localised hypermutation is being unlocked by the investigation of whole genome sequences of disease isolates, analysis of clinical samples and use of model systems. A contrast is presented between the problematical nature of analysing simple sequence repeats in next generation sequencing data and in simpler, pragmatic PCR-based approaches. Specific examples are presented of the potential relevance of this localized hypermutation to meningococcal pathogenesis. This leads us to speculate on the future prospects for unravelling how hypermutable mechanisms may contribute to the transmission, spread and persistence of bacterial pathogens. Full article
(This article belongs to the Special Issue Bacterial Pathogenomics: From Technology to Application)
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353 KiB  
Review
Identifying Pathogenicity Islands in Bacterial Pathogenomics Using Computational Approaches
by Dongsheng Che, Mohammad Shabbir Hasan and Bernard Chen
Pathogens 2014, 3(1), 36-56; https://doi.org/10.3390/pathogens3010036 - 13 Jan 2014
Cited by 51 | Viewed by 12806
Abstract
High-throughput sequencing technologies have made it possible to study bacteria through analyzing their genome sequences. For instance, comparative genome sequence analyses can reveal the phenomenon such as gene loss, gene gain, or gene exchange in a genome. By analyzing pathogenic bacterial genomes, we [...] Read more.
High-throughput sequencing technologies have made it possible to study bacteria through analyzing their genome sequences. For instance, comparative genome sequence analyses can reveal the phenomenon such as gene loss, gene gain, or gene exchange in a genome. By analyzing pathogenic bacterial genomes, we can discover that pathogenic genomic regions in many pathogenic bacteria are horizontally transferred from other bacteria, and these regions are also known as pathogenicity islands (PAIs). PAIs have some detectable properties, such as having different genomic signatures than the rest of the host genomes, and containing mobility genes so that they can be integrated into the host genome. In this review, we will discuss various pathogenicity island-associated features and current computational approaches for the identification of PAIs. Existing pathogenicity island databases and related computational resources will also be discussed, so that researchers may find it to be useful for the studies of bacterial evolution and pathogenicity mechanisms. Full article
(This article belongs to the Special Issue Bacterial Pathogenomics: From Technology to Application)
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Other

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301 KiB  
Opinion
Culture-Independence for Surveillance and Epidemiology
by Benjamin C. Kirkup, Jr.
Pathogens 2013, 2(3), 556-570; https://doi.org/10.3390/pathogens2030556 - 24 Sep 2013
Cited by 4 | Viewed by 6376
Abstract
Culture-independent methods in microbiology (quantitative PCR (qPCR), sequencing, microarrays, direct from sample matrix assisted laser desorption/ionization time of flight mass spectroscopy (MALDI-TOF MS), etc.) are disruptive technology. Rather than providing the same results as culture-based methods more quickly, more cheaply or with [...] Read more.
Culture-independent methods in microbiology (quantitative PCR (qPCR), sequencing, microarrays, direct from sample matrix assisted laser desorption/ionization time of flight mass spectroscopy (MALDI-TOF MS), etc.) are disruptive technology. Rather than providing the same results as culture-based methods more quickly, more cheaply or with improved accuracy, they reveal an unexpected diversity of microbes and illuminate dark corners of undiagnosed disease. At times, they overturn existing definitions of presumably well-understood infections, generating new requirements for clinical diagnosis, surveillance and epidemiology. However, current diagnostic microbiology, infection control and epidemiology rest principally on culture methods elegantly optimized by clinical laboratorians. The clinical significance is interwoven; the new methods are out of context, difficult to interpret and impossible to act upon. Culture-independent diagnostics and surveillance methods will not be deployed unless the reported results can be used to select specific therapeutics or infection control measures. To cut the knots surrounding the adoption of culture-independent methods in medical microbiology, culture-dependent methods should be supported by consistent culture-independent methods providing the microbial context. This will temper existing biases and motivate appropriate scrutiny of the older methods and results. Full article
(This article belongs to the Special Issue Bacterial Pathogenomics: From Technology to Application)
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