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Genomics: Infectious Disease and Host-Pathogen Interaction 2.0
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Genomics: Infectious Disease and Host-Pathogen Interaction 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (20 March 2023) | Viewed by 21399

Special Issue Editor

Dr. Franklin W.N. Chow

E-Mail Website
Guest Editor
Department of Health Technology and Informatics, Hong Kong Polytechnic University, Hong Kong, China
Interests: emerging infectious diseases; host-pathogen interactions; extracellular vesicles; pathogen genomics and evolution; RNA Biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Infectious diseases are disorders caused by pathogens, such as bacteria, viruses, fungi or parasites, and pose a serious threat to humans, animals, and plants. Pathogens can interact with the host to suppress or evade the host immune system in order to establish and disseminate infections.

Unique genome features contribute largely to the events of host–pathogen interactions, governing the virulence level of the pathogens and the infection severity of the host. With the advancement of NGS and nanopore sequencings, it is now highly cost-effective to pursue genomic and transcriptomic studies. Recent research has shown that host–pathogen interactions can be bi-directionally modulated by small RNAs that come from unique genome loci. Under the current COVID-19 pandemic, there has been a surge in development of SARS-CoV-2 detection methods based on studying the phylogenomics and mutations of viral genomes.

We invite researchers to contribute original research articles and reviews focused on different genomic aspects of i) infectious diseases, and ii) host–pathogen interactions.

Topics of interest include, but are not limited to, the following:

  • Genomics and transcriptomics;
  • Phylogenetics and evolution;
  • Small RNA regulations;
  • RNA biology (e.g., dual-RNA-seq);
  • Molecular pathogenesis;
  • Molecular detection.

Dr. Franklin W.N. Chow
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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.

Keywords

  • infectious diseases
  • NGS
  • small RNA
  • host–pathogen interaction
  • pathogen detection
  • viruses
  • fungi
  • parasites
  • bacteria
  • evolution

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Related Special Issue

Published Papers (7 papers)

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Research

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23 pages, 4361 KiB  
Article
The Succession of the Cellulolytic Microbial Community from the Soil during Oat Straw Decomposition
by Anastasiia K. Kimeklis, Grigory V. Gladkov, Olga V. Orlova, Alexey M. Afonin, Emma S. Gribchenko, Tatiana S. Aksenova, Arina A. Kichko, Alexander G. Pinaev and Evgeny E. Andronov
Int. J. Mol. Sci. 2023, 24(7), 6342; https://doi.org/10.3390/ijms24076342 - 28 Mar 2023
Cited by 10 | Viewed by 2539
Abstract
The process of straw decomposition is dynamic and is accompanied by the succession of the microbial decomposing community, which is driven by poorly understood interactions between microorganisms. Soil is a complex ecological niche, and the soil microbiome can serve as a source of [...] Read more.
The process of straw decomposition is dynamic and is accompanied by the succession of the microbial decomposing community, which is driven by poorly understood interactions between microorganisms. Soil is a complex ecological niche, and the soil microbiome can serve as a source of potentially active cellulolytic microorganisms. Here, we performed an experiment on the de novo colonization of oat straw by the soil microbial community by placing nylon bags with sterilized oat straw in the pots filled with chernozem soil and incubating them for 6 months. The aim was to investigate the changes in decomposer microbiota during this process using conventional sequencing techniques. The bacterial succession during straw decomposition occurred in three phases: the early phase (first month) was characterized by high microbial activity and low diversity, the middle phase (second to third month) was characterized by low activity and low diversity, and the late phase (fourth to sixth months) was characterized by low activity and high diversity. Analysis of amplicon sequencing data revealed three groups of co-changing phylotypes corresponding to these phases. The early active phase was abundant in the cellulolytic members from Pseudomonadota, Bacteroidota, Bacillota, and Actinobacteriota for bacteria and Ascomycota for fungi, and most of the primary phylotypes were gone by the end of the phase. The second intermediate phase was marked by the set of phylotypes from the same phyla persisting in the community. In the mature community of the late phase, apart from the core phylotypes, non-cellulolytic members from Bdellovibrionota, Myxococcota, Chloroflexota, and Thermoproteota appeared. Full metagenome sequencing of the microbial community from the end of the middle phase confirmed that major bacterial and fungal members of this consortium had genes of glycoside hydrolases (GH) connected to cellulose and chitin degradation. The real-time analysis of the selection of these genes showed that their representation varied between phases, and this occurred under the influence of the host, and not the GH family factor. Our findings demonstrate that soil microbial community may act as an efficient source of cellulolytic microorganisms and that colonization of the cellulolytic substrate occurs in several phases, each characterized by its own taxonomic and functional profile. Full article
(This article belongs to the Special Issue Genomics: Infectious Disease and Host-Pathogen Interaction 2.0)
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20 pages, 2592 KiB  
Article
Comparison of Phenotype and Genotype Virulence and Antimicrobial Factors of Salmonella Typhimurium Isolated from Human Milk
by Joanna Pławińska-Czarnak, Karolina Wódz, Magdalena Guzowska, Elżbieta Rosiak, Tomasz Nowak, Zuzanna Strzałkowska, Adam Kwieciński, Piotr Kwieciński and Krzysztof Anusz
Int. J. Mol. Sci. 2023, 24(6), 5135; https://doi.org/10.3390/ijms24065135 - 7 Mar 2023
Cited by 2 | Viewed by 2789
Abstract
Salmonella is a common foodborne infection. Many serovars belonging to Salmonella enterica subsp. enterica are present in the gut of various animal species. They can cause infection in human infants via breast milk or cross-contamination with powdered milk. In the present study, Salmonella [...] Read more.
Salmonella is a common foodborne infection. Many serovars belonging to Salmonella enterica subsp. enterica are present in the gut of various animal species. They can cause infection in human infants via breast milk or cross-contamination with powdered milk. In the present study, Salmonella BO was isolated from human milk in accordance with ISO 6579-1:2017 standards and sequenced using whole-genome sequencing (WGS), followed by serosequencing and genotyping. The results also allowed its pathogenicity to be predicted. The WGS results were compared with the bacterial phenotype. The isolated strain was found to be Salmonella enterica subsp. enterica serovar Typhimurium 4:i:1,2_69M (S. Typhimurium 69M); it showed a very close similarity to S. enterica subsp. enterica serovar Typhimurium LT2. Bioinformatics sequence analysis detected eleven SPIs (SPI-1, SPI-2, SPI-3, SPI-4, SPI-5, SPI-9, SPI-12, SPI-13, SPI-14, C63PI, CS54_island). Significant changes in gene sequences were noted, causing frameshift mutations in yeiG, rfbP, fumA, yeaL, ybeU (insertion) and lpfD, avrA, ratB, yacH (deletion). The sequences of several proteins were significantly different from those coded in the reference genome; their three-dimensional structure was predicted and compared with reference proteins. Our findings indicate the presence of a number of antimicrobial resistance genes that do not directly imply an antibiotic resistance phenotype. Full article
(This article belongs to the Special Issue Genomics: Infectious Disease and Host-Pathogen Interaction 2.0)
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24 pages, 3426 KiB  
Article
Genomic Distribution of Pro-Virulent cpdB-like Genes in Eubacteria and Comparison of the Enzyme Specificity of CpdB-like Proteins from Salmonella enterica, Escherichia coli and Streptococcus suis
by João Meireles Ribeiro, José Canales, María Jesús Costas, Alicia Cabezas, Rosa María Pinto, Miguel García-Díaz, Paloma Martín-Cordero and José Carlos Cameselle
Int. J. Mol. Sci. 2023, 24(4), 4150; https://doi.org/10.3390/ijms24044150 - 19 Feb 2023
Cited by 4 | Viewed by 1697
Abstract
The cpdB gene is pro-virulent in avian pathogenic Escherichia coli and in Salmonella enterica, where it encodes a periplasmic protein named CpdB. It is structurally related to cell wall-anchored proteins, CdnP and SntA, encoded by the also pro-virulent cdnP and sntA genes [...] Read more.
The cpdB gene is pro-virulent in avian pathogenic Escherichia coli and in Salmonella enterica, where it encodes a periplasmic protein named CpdB. It is structurally related to cell wall-anchored proteins, CdnP and SntA, encoded by the also pro-virulent cdnP and sntA genes of Streptococcus agalactiae and Streptococcus suis, respectively. CdnP and SntA effects are due to extrabacterial hydrolysis of cyclic-di-AMP, and to complement action interference. The mechanism of CpdB pro-virulence is unknown, although the protein from non-pathogenic E. coli hydrolyzes cyclic dinucleotides. Considering that the pro-virulence of streptococcal CpdB-like proteins is mediated by c-di-AMP hydrolysis, S. enterica CpdB activity was tested as a phosphohydrolase of 3′-nucleotides, 2′,3′-cyclic mononucleotides, linear and cyclic dinucleotides, and cyclic tetra- and hexanucleotides. The results help to understand cpdB pro-virulence in S. enterica and are compared with E. coli CpdB and S. suis SntA, including the activity of the latter on cyclic-tetra- and hexanucleotides reported here for the first time. On the other hand, since CpdB-like proteins are relevant to host-pathogen interactions, the presence of cpdB-like genes was probed in eubacterial taxa by TblastN analysis. The non-homogeneous genomic distribution revealed taxa with cpdB-like genes present or absent, identifying eubacteria and plasmids where they can be relevant. Full article
(This article belongs to the Special Issue Genomics: Infectious Disease and Host-Pathogen Interaction 2.0)
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25 pages, 2626 KiB  
Article
The Pseudomonas aeruginosa RpoH (σ32) Regulon and Its Role in Essential Cellular Functions, Starvation Survival, and Antibiotic Tolerance
by Kerry S. Williamson, Mensur Dlakić, Tatsuya Akiyama and Michael J. Franklin
Int. J. Mol. Sci. 2023, 24(2), 1513; https://doi.org/10.3390/ijms24021513 - 12 Jan 2023
Cited by 4 | Viewed by 2850
Abstract
The bacterial heat-shock response is regulated by the alternative sigma factor, σ32 (RpoH), which responds to misfolded protein stress and directs the RNA polymerase to the promoters for genes required for protein refolding or degradation. In P. aeruginosa, RpoH is essential [...] Read more.
The bacterial heat-shock response is regulated by the alternative sigma factor, σ32 (RpoH), which responds to misfolded protein stress and directs the RNA polymerase to the promoters for genes required for protein refolding or degradation. In P. aeruginosa, RpoH is essential for viability under laboratory growth conditions. Here, we used a transcriptomics approach to identify the genes of the RpoH regulon, including RpoH-regulated genes that are essential for P. aeruginosa. We placed the rpoH gene under control of the arabinose-inducible PBAD promoter, then deleted the chromosomal rpoH allele. This allowed transcriptomic analysis of the RpoH (σ32) regulon following a short up-shift in the cellular concentration of RpoH by arabinose addition, in the absence of a sudden change in temperature. The P. aeruginosa ∆rpoH (PBAD-rpoH) strain grew in the absence of arabinose, indicating that some rpoH expression occurred without arabinose induction. When arabinose was added, the rpoH mRNA abundance of P. aeruginosa ∆rpoH (PBAD-rpoH) measured by RT-qPCR increased five-fold within 15 min of arabinose addition. Transcriptome results showed that P. aeruginosa genes required for protein repair or degradation are induced by increased RpoH levels, and that many genes essential for P. aeruginosa growth are induced by RpoH. Other stress response genes induced by RpoH are involved in damaged nucleic acid repair and in amino acid metabolism. Annotation of the hypothetical proteins under RpoH control included proteins that may play a role in antibiotic resistances and in non-ribosomal peptide synthesis. Phenotypic analysis of P. aeruginosa ∆rpoH (PBAD-rpoH) showed that it is impaired in its ability to survive during starvation compared to the wild-type strain. P. aeruginosa ∆rpoH (PBAD-rpoH) also had increased sensitivity to aminoglycoside antibiotics, but not to other classes of antibiotics, whether cultured planktonically or in biofilms. The enhanced aminoglycoside sensitivity of the mutant strain may be due to indirect effects, such as the build-up of toxic misfolded proteins, or to the direct effect of genes, such as aminoglycoside acetyl transferases, that are regulated by RpoH. Overall, the results demonstrate that RpoH regulates genes that are essential for viability of P. aeruginosa, that it protects P. aeruginosa from damage from aminoglycoside antibiotics, and that it is required for survival during nutrient-limiting conditions. Full article
(This article belongs to the Special Issue Genomics: Infectious Disease and Host-Pathogen Interaction 2.0)
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12 pages, 1854 KiB  
Article
Comparison of Bioluminescent Substrates in Natural Infection Models of Neglected Parasitic Diseases
by Sarah Hendrickx, Dimitri Bulté, Dorien Mabille, Roxanne Mols, Mathieu Claes, Kayhan Ilbeigi, Rokaya Ahmad, Laura Dirkx, Sara I. Van Acker and Guy Caljon
Int. J. Mol. Sci. 2022, 23(24), 16074; https://doi.org/10.3390/ijms232416074 - 16 Dec 2022
Cited by 1 | Viewed by 1737
Abstract
The application of in vivo bioluminescent imaging in infectious disease research has significantly increased over the past years. The detection of transgenic parasites expressing wildtype firefly luciferase is however hampered by a relatively low and heterogeneous tissue penetrating capacity of emitted light. Solutions [...] Read more.
The application of in vivo bioluminescent imaging in infectious disease research has significantly increased over the past years. The detection of transgenic parasites expressing wildtype firefly luciferase is however hampered by a relatively low and heterogeneous tissue penetrating capacity of emitted light. Solutions are sought by using codon-optimized red-shifted luciferases that yield higher expression levels and produce relatively more red or near-infrared light, or by using modified bioluminescent substrates with enhanced cell permeability and improved luminogenic or pharmacokinetic properties. In this study, the in vitro and in vivo efficacy of two modified bioluminescent substrates, CycLuc1 and AkaLumine-HCl, were compared with that of D-luciferin as a gold standard. Comparisons were made in experimental and insect-transmitted animal models of leishmaniasis (caused by intracellular Leishmania species) and African trypanosomiasis (caused by extracellular Trypanosoma species), using parasite strains expressing the red-shifted firefly luciferase PpyRE9. Although the luminogenic properties of AkaLumine-HCl and D-luciferin for in vitro parasite detection were comparable at equal substrate concentrations, AkaLumine-HCl proved to be unsuitable for in vivo infection follow-up due to high background signals in the liver. CycLuc1 presented a higher in vitro luminescence compared to the other substrates and proved to be highly efficacious in vivo, even at a 20-fold lower dose than D-luciferin. This efficacy was consistent across infections with the herein included intracellular and extracellular parasitic organisms. It can be concluded that CycLuc1 is an excellent and broadly applicable alternative for D-luciferin, requiring significantly lower doses for in vivo bioluminescent imaging in rodent models of leishmaniasis and African trypanosomiasis. Full article
(This article belongs to the Special Issue Genomics: Infectious Disease and Host-Pathogen Interaction 2.0)
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12 pages, 638 KiB  
Article
An Improved Real-Time Viability PCR Assay to Detect Salmonella in a Culture-Independent Era
by Surangi H. Thilakarathna, Taryn Stokowski and Linda Chui
Int. J. Mol. Sci. 2022, 23(23), 14708; https://doi.org/10.3390/ijms232314708 - 25 Nov 2022
Cited by 4 | Viewed by 5601
Abstract
Viability PCR (vPCR) uses a DNA intercalating dye to irreversibly bind double-stranded DNA from organisms with compromised cell membranes. This allows the selective amplification of DNA from intact cells. An optimized vPCR protocol should minimize false positives (DNA from compromised cells not fully [...] Read more.
Viability PCR (vPCR) uses a DNA intercalating dye to irreversibly bind double-stranded DNA from organisms with compromised cell membranes. This allows the selective amplification of DNA from intact cells. An optimized vPCR protocol should minimize false positives (DNA from compromised cells not fully removed) and false negatives (live cell DNA bound by the dye). We aimed to optimize a vPCR protocol using PMAxx™ as the intercalating agent and Salmonella Enteritidis as the target organism. To do this, we studied (1) single vs. sequential PMAxx™ addition; (2) a wash step post-PMAxx™ treatment; (3) a change of tube post-treatment before DNA extraction. The single vs. sequential PMAxx™ addition showed no difference. Results signified that PMAxx™ potentially attached to polypropylene tube walls and bound the released DNA from PMA-treated live cells when lysed in the same tube. A wash step was ineffective but transfer of the treated live cells to a new tube minimized these false-negative results. Our optimized protocol eliminated 108 CFU/mL heat-killed cell DNA in the presence of different live cell dilutions without compromising the amplification of the live cells, minimizing false positives. With further improvements, vPCR has great potential as a culture-independent diagnostic tool. Full article
(This article belongs to the Special Issue Genomics: Infectious Disease and Host-Pathogen Interaction 2.0)
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Review

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16 pages, 857 KiB  
Review
Pathogenicity of Type I Interferons in Mycobacterium tuberculosis
by Akaash Mundra, Aram Yegiazaryan, Haig Karsian, Dijla Alsaigh, Victor Bonavida, Mitchell Frame, Nicole May, Areg Gargaloyan, Arbi Abnousian and Vishwanath Venketaraman
Int. J. Mol. Sci. 2023, 24(4), 3919; https://doi.org/10.3390/ijms24043919 - 15 Feb 2023
Cited by 8 | Viewed by 3408
Abstract
Tuberculosis (TB) is a leading cause of mortality due to infectious disease and rates have increased during the emergence of COVID-19, but many of the factors determining disease severity and progression remain unclear. Type I Interferons (IFNs) have diverse effector functions that regulate [...] Read more.
Tuberculosis (TB) is a leading cause of mortality due to infectious disease and rates have increased during the emergence of COVID-19, but many of the factors determining disease severity and progression remain unclear. Type I Interferons (IFNs) have diverse effector functions that regulate innate and adaptive immunity during infection with microorganisms. There is well-documented literature on type I IFNs providing host defense against viruses; however, in this review, we explore the growing body of work that indicates high levels of type I IFNs can have detrimental effects to a host fighting TB infection. We report findings that increased type I IFNs can affect alveolar macrophage and myeloid function, promote pathological neutrophil extracellular trap responses, inhibit production of protective prostaglandin 2, and promote cytosolic cyclic GMP synthase inflammation pathways, and discuss many other relevant findings. Full article
(This article belongs to the Special Issue Genomics: Infectious Disease and Host-Pathogen Interaction 2.0)
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