Biomolecules

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12 pages, 1454 KiB

Open AccessEditor’s ChoiceArticle

Role of the MDR Efflux Pump AcrAB in Epithelial Cell Invasion by Shigella flexneri

by Marco Coluccia, Aude Béranger, Rita Trirocco, Giulia Fanelli, Francesco Zanzi, Bianca Colonna, Milena Grossi, Gianni Prosseda and Martina Pasqua

Biomolecules 2023, 13(5), 823; https://doi.org/10.3390/biom13050823 - 11 May 2023

Cited by 5 | Viewed by 2295

Abstract

The tripartite complex AcrAB-TolC is the major RND pump in Escherichia coli and other Enterobacteriaceae, including Shigella, the etiological agent of bacillary dysentery. In addition to conferring resistance to many classes of antibiotics, AcrAB plays a role in the pathogenesis and virulence [...] Read more.

The tripartite complex AcrAB-TolC is the major RND pump in Escherichia coli and other Enterobacteriaceae, including Shigella, the etiological agent of bacillary dysentery. In addition to conferring resistance to many classes of antibiotics, AcrAB plays a role in the pathogenesis and virulence of several bacterial pathogens. Here, we report data demonstrating that AcrAB specifically contributes to Shigella flexneri invasion of epithelial cells. We found that deletion of both acrA and acrB genes causes reduced survival of S. flexneri M90T strain within Caco-2 epithelial cells and prevents cell-to-cell spread of the bacteria. Infections with single deletion mutant strains indicate that both AcrA and AcrB favor the viability of the intracellular bacteria. Finally, we were able to further confirm the requirement of the AcrB transporter activity for intraepithelial survival by using a specific EP inhibitor. Overall, the data from the present study expand the role of the AcrAB pump to an important human pathogen, such as Shigella, and add insights into the mechanism governing the Shigella infection process. Full article

(This article belongs to the Special Issue Theme Issue Honoring Scientist Louis Pasteur on His 200th Birthday)

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18 pages, 2756 KiB

Open AccessArticle

Defining Two Chemosensory Arrays in Shewanella oneidensis

by Emma M. Fortier, Sophie Bouillet, Pascale Infossi, Amine Ali Chaouche, Leon Espinosa, Marie-Thérèse Giudici-Orticoni, Emilia M. F. Mauriello and Chantal Iobbi-Nivol

Biomolecules 2023, 13(1), 21; https://doi.org/10.3390/biom13010021 - 22 Dec 2022

Cited by 1 | Viewed by 2008

Abstract

Shewanella oneidensis has 2 functional chemosensory systems named Che1 and Che3, and 27 chemoreceptors. Che3 is dedicated to chemotaxis while Che1 could be involved in RpoS post-translational regulation. In this study, we have shown that two chemoreceptors Aer2so and McpAso, genetically related to [...] Read more.

Shewanella oneidensis has 2 functional chemosensory systems named Che1 and Che3, and 27 chemoreceptors. Che3 is dedicated to chemotaxis while Che1 could be involved in RpoS post-translational regulation. In this study, we have shown that two chemoreceptors Aer2so and McpAso, genetically related to the Che1 system, form distinct core-signaling units and signal to Che1 and Che3, respectively. Moreover, we observed that Aer2so is a cytoplasmic dynamic chemoreceptor that, when in complex with CheA1 and CheW1, localizes at the two poles and the centre of the cells. Altogether, the results obtained indicate that Che1 and Che3 systems are interconnected by these two chemoreceptors allowing a global response for bacterial survival. Full article

(This article belongs to the Special Issue Theme Issue Honoring Scientist Louis Pasteur on His 200th Birthday)

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27 pages, 3242 KiB

Open AccessEditor’s ChoiceArticle

A Study on the Nature of SARS-CoV-2 Using the Shell Disorder Models: Reproducibility, Evolution, Spread, and Attenuation

by Gerard Kian-Meng Goh, A. Keith Dunker, James A. Foster and Vladimir N. Uversky

Biomolecules 2022, 12(10), 1353; https://doi.org/10.3390/biom12101353 - 23 Sep 2022

Cited by 3 | Viewed by 2336

Abstract

The basic tenets of the shell disorder model (SDM) as applied to COVID-19 are that the harder outer shell of the virus shell (lower PID—percentage of intrinsic disorder—of the membrane protein M, PID_M) and higher flexibility of the inner shell (higher [...] Read more.

The basic tenets of the shell disorder model (SDM) as applied to COVID-19 are that the harder outer shell of the virus shell (lower PID—percentage of intrinsic disorder—of the membrane protein M, PID_M) and higher flexibility of the inner shell (higher PID of the nucleocapsid protein N, PID_N) are correlated with the contagiousness and virulence, respectively. M protects the virion from the anti-microbial enzymes in the saliva and mucus. N disorder is associated with the rapid replication of the virus. SDM predictions are supported by two experimental observations. The first observation demonstrated lesser and greater presence of the Omicron particles in the lungs and bronchial tissues, respectively, as there is a greater level of mucus in the bronchi. The other observation revealed that there are lower viral loads in 2017-pangolin-CoV, which is predicted to have similarly low PID_N as Omicron. The abnormally hard M, which is very rarely seen in coronaviruses, arose from the fecal–oral behaviors of pangolins via exposure to buried feces. Pangolins provide an environment for coronavirus (CoV) attenuation, which is seen in Omicron. Phylogenetic study using M shows that COVID-19-related bat-CoVs from Laos and Omicron are clustered in close proximity to pangolin-CoVs, which suggests the recurrence of interspecies transmissions. Hard M may have implications for long COVID-19, with immune systems having difficulty degrading viral proteins/particles. Full article

(This article belongs to the Special Issue Theme Issue Honoring Scientist Louis Pasteur on His 200th Birthday)

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17 pages, 283 KiB

Open AccessArticle

Ethanolic Fermentation of Rye Mashes: Factors Influencing the Formation of Aldehydes and Process Efficiency

by Katarzyna Pielech-Przybylska, Maria Balcerek, Maciej Klebeko, Urszula Dziekońska-Kubczak and Mariusz Hebdzyński

Biomolecules 2022, 12(8), 1085; https://doi.org/10.3390/biom12081085 - 6 Aug 2022

Cited by 1 | Viewed by 2158

Abstract

High concentrations of aldehydes may result in poor-quality agricultural distillate. We investigate the influence of the method of mash preparation, the initial pH of the mashes, and different yeast strains on the fermentation efficiency and concentration of aldehydes from C2 (acetaldehyde) to C7 [...] Read more.

High concentrations of aldehydes may result in poor-quality agricultural distillate. We investigate the influence of the method of mash preparation, the initial pH of the mashes, and different yeast strains on the fermentation efficiency and concentration of aldehydes from C2 (acetaldehyde) to C7 (enanthaldehyde) in rye mashes. The tested factors were revealed to have a differentiated influence on both the process efficiency and the concentrations of aldehydes, especially in the case of the dominant acetaldehyde. Mashes obtained from steamed rye grain showed significantly higher fermentation efficiencies than those prepared by the pressureless method. Increasing the pH of the sweet mashes from 4.5 to 6.0 resulted in significantly higher concentrations of acetaldehyde, especially in the case of steamed rye grain. Moreover, an increase in the concentrations of other aldehydes, i.e., from C3 (propionaldehyde) to C5 (valer- and isovaleraldehyde) was observed. A high fermentation efficiency and the lowest acetaldehyde concentrations were obtained from steamed rye mashes with an initial pH of 4.5, fermented using the yeast strains DistilaMax GW and DistilaMax HT. DistilaMax HT yeast also provided a relatively low concentration of acetaldehyde in mashes with an initial pH in the range of 4.5–5.5 prepared by the energy-saving pressureless method. Full article

(This article belongs to the Special Issue Theme Issue Honoring Scientist Louis Pasteur on His 200th Birthday)

26 pages, 5700 KiB

Open AccessArticle

Targeting the YXXΦ Motifs of the SARS Coronaviruses 1 and 2 ORF3a Peptides by In Silico Analysis to Predict Novel Virus—Host Interactions

by Athanassios Kakkanas, Eirini Karamichali, Efthymia Ioanna Koufogeorgou, Stathis D. Kotsakis, Urania Georgopoulou and Pelagia Foka

Biomolecules 2022, 12(8), 1052; https://doi.org/10.3390/biom12081052 - 29 Jul 2022

Cited by 4 | Viewed by 2393

Abstract

The emerging SARS-CoV and SARS-CoV-2 belong to the family of “common cold” RNA coronaviruses, and they are responsible for the 2003 epidemic and the current pandemic with over 6.3 M deaths worldwide. The ORF3a gene is conserved in both viruses and codes for [...] Read more.

The emerging SARS-CoV and SARS-CoV-2 belong to the family of “common cold” RNA coronaviruses, and they are responsible for the 2003 epidemic and the current pandemic with over 6.3 M deaths worldwide. The ORF3a gene is conserved in both viruses and codes for the accessory protein ORF3a, with unclear functions, possibly related to viral virulence and pathogenesis. The tyrosine-based YXXΦ motif (Φ: bulky hydrophobic residue—L/I/M/V/F) was originally discovered to mediate clathrin-dependent endocytosis of membrane-spanning proteins. Many viruses employ the YXXΦ motif to achieve efficient receptor-guided internalisation in host cells, maintain the structural integrity of their capsids and enhance viral replication. Importantly, this motif has been recently identified on the ORF3a proteins of SARS-CoV and SARS-CoV-2. Given that the ORF3a aa sequence is not fully conserved between the two SARS viruses, we aimed to map in silico structural differences and putative sequence-driven alterations of regulatory elements within and adjacently to the YXXΦ motifs that could predict variations in ORF3a functions. Using robust bioinformatics tools, we investigated the presence of relevant post-translational modifications and the YXXΦ motif involvement in protein-protein interactions. Our study suggests that the predicted YXXΦ-related features may confer specific—yet to be discovered—functions to ORF3a proteins, significant to the new virus and related to enhanced propagation, host immune regulation and virulence. Full article

(This article belongs to the Special Issue Theme Issue Honoring Scientist Louis Pasteur on His 200th Birthday)

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Review

Jump to: Research

20 pages, 2313 KiB

Open AccessReview

Bacterial Spore-Based Delivery System: 20 Years of a Versatile Approach for Innovative Vaccines

by Rachele Isticato

Biomolecules 2023, 13(6), 947; https://doi.org/10.3390/biom13060947 - 6 Jun 2023

Cited by 4 | Viewed by 2815

Abstract

Mucosal vaccines offer several advantages over injectable conventional vaccines, such as the induction of adaptive immunity, with secretory IgA production at the entry site of most pathogens, and needle-less vaccinations. Despite their potential, only a few mucosal vaccines are currently used. Developing new [...] Read more.

Mucosal vaccines offer several advantages over injectable conventional vaccines, such as the induction of adaptive immunity, with secretory IgA production at the entry site of most pathogens, and needle-less vaccinations. Despite their potential, only a few mucosal vaccines are currently used. Developing new effective mucosal vaccines strongly relies on identifying innovative antigens, efficient adjuvants, and delivery systems. Several approaches based on phages, bacteria, or nanoparticles have been proposed to deliver antigens to mucosal surfaces. Bacterial spores have also been considered antigen vehicles, and various antigens have been successfully exposed on their surface. Due to their peculiar structure, spores conjugate the advantages of live microorganisms with synthetic nanoparticles. When mucosally administered, spores expressing antigens have been shown to induce antigen-specific, protective immune responses. This review accounts for recent progress in the formulation of spore-based mucosal vaccines, describing a spore’s structure, specifically the spore surface, and the diverse approaches developed to improve its efficiency as a vehicle for heterologous antigen presentation. Full article

(This article belongs to the Special Issue Theme Issue Honoring Scientist Louis Pasteur on His 200th Birthday)

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16 pages, 3638 KiB

Open AccessEditor’s ChoiceReview

Recent Advances in Peptidoglycan Synthesis and Regulation in Bacteria

by Anne Galinier, Clémentine Delan-Forino, Elodie Foulquier, Hakima Lakhal and Frédérique Pompeo

Biomolecules 2023, 13(5), 720; https://doi.org/10.3390/biom13050720 - 22 Apr 2023

Cited by 17 | Viewed by 5741

Abstract

Bacteria must synthesize their cell wall and membrane during their cell cycle, with peptidoglycan being the primary component of the cell wall in most bacteria. Peptidoglycan is a three-dimensional polymer that enables bacteria to resist cytoplasmic osmotic pressure, maintain their cell shape and [...] Read more.

Bacteria must synthesize their cell wall and membrane during their cell cycle, with peptidoglycan being the primary component of the cell wall in most bacteria. Peptidoglycan is a three-dimensional polymer that enables bacteria to resist cytoplasmic osmotic pressure, maintain their cell shape and protect themselves from environmental threats. Numerous antibiotics that are currently used target enzymes involved in the synthesis of the cell wall, particularly peptidoglycan synthases. In this review, we highlight recent progress in our understanding of peptidoglycan synthesis, remodeling, repair, and regulation in two model bacteria: the Gram-negative Escherichia coli and the Gram-positive Bacillus subtilis. By summarizing the latest findings in this field, we hope to provide a comprehensive overview of peptidoglycan biology, which is critical for our understanding of bacterial adaptation and antibiotic resistance. Full article

(This article belongs to the Special Issue Theme Issue Honoring Scientist Louis Pasteur on His 200th Birthday)

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27 pages, 3169 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Archaea as a Model System for Molecular Biology and Biotechnology

by Federica De Lise, Roberta Iacono, Marco Moracci, Andrea Strazzulli and Beatrice Cobucci-Ponzano

Biomolecules 2023, 13(1), 114; https://doi.org/10.3390/biom13010114 - 6 Jan 2023

Cited by 10 | Viewed by 4743

Abstract

Archaea represents the third domain of life, displaying a closer relationship with eukaryotes than bacteria. These microorganisms are valuable model systems for molecular biology and biotechnology. In fact, nowadays, methanogens, halophiles, thermophilic euryarchaeota, and crenarchaeota are the four groups of archaea for which [...] Read more.

Archaea represents the third domain of life, displaying a closer relationship with eukaryotes than bacteria. These microorganisms are valuable model systems for molecular biology and biotechnology. In fact, nowadays, methanogens, halophiles, thermophilic euryarchaeota, and crenarchaeota are the four groups of archaea for which genetic systems have been well established, making them suitable as model systems and allowing for the increasing study of archaeal genes’ functions. Furthermore, thermophiles are used to explore several aspects of archaeal biology, such as stress responses, DNA replication and repair, transcription, translation and its regulation mechanisms, CRISPR systems, and carbon and energy metabolism. Extremophilic archaea also represent a valuable source of new biomolecules for biological and biotechnological applications, and there is growing interest in the development of engineered strains. In this review, we report on some of the most important aspects of the use of archaea as a model system for genetic evolution, the development of genetic tools, and their application for the elucidation of the basal molecular mechanisms in this domain of life. Furthermore, an overview on the discovery of new enzymes of biotechnological interest from archaea thriving in extreme environments is reported. Full article

(This article belongs to the Special Issue Theme Issue Honoring Scientist Louis Pasteur on His 200th Birthday)

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20 pages, 1127 KiB

Open AccessEditor’s ChoiceReview

Roles of Two-Component Signal Transduction Systems in Shigella Virulence

by Martina Pasqua, Marco Coluccia, Yoko Eguchi, Toshihide Okajima, Milena Grossi, Gianni Prosseda, Ryutaro Utsumi and Bianca Colonna

Biomolecules 2022, 12(9), 1321; https://doi.org/10.3390/biom12091321 - 18 Sep 2022

Cited by 14 | Viewed by 4667

Abstract

Two-component signal transduction systems (TCSs) are widespread types of protein machinery, typically consisting of a histidine kinase membrane sensor and a cytoplasmic transcriptional regulator that can sense and respond to environmental signals. TCSs are responsible for modulating genes involved in a multitude of [...] Read more.

Two-component signal transduction systems (TCSs) are widespread types of protein machinery, typically consisting of a histidine kinase membrane sensor and a cytoplasmic transcriptional regulator that can sense and respond to environmental signals. TCSs are responsible for modulating genes involved in a multitude of bacterial functions, including cell division, motility, differentiation, biofilm formation, antibiotic resistance, and virulence. Pathogenic bacteria exploit the capabilities of TCSs to reprogram gene expression according to the different niches they encounter during host infection. This review focuses on the role of TCSs in regulating the virulence phenotype of Shigella, an intracellular pathogen responsible for severe human enteric syndrome. The pathogenicity of Shigella is the result of the complex action of a wide number of virulence determinants located on the chromosome and on a large virulence plasmid. In particular, we will discuss how five TCSs, EnvZ/OmpR, CpxA/CpxR, ArcB/ArcA, PhoQ/PhoP, and EvgS/EvgA, contribute to linking environmental stimuli to the expression of genes related to virulence and fitness within the host. Considering the relevance of TCSs in the expression of virulence in pathogenic bacteria, the identification of drugs that inhibit TCS function may represent a promising approach to combat bacterial infections. Full article

(This article belongs to the Special Issue Theme Issue Honoring Scientist Louis Pasteur on His 200th Birthday)

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25 pages, 8303 KiB

Open AccessEditor’s ChoiceReview

Degradation of Exogenous Fatty Acids in Escherichia coli

by Viola Pavoncello, Frédéric Barras and Emmanuelle Bouveret

Biomolecules 2022, 12(8), 1019; https://doi.org/10.3390/biom12081019 - 22 Jul 2022

Cited by 22 | Viewed by 4901

Abstract

Many bacteria possess all the machineries required to grow on fatty acids (FA) as a unique source of carbon and energy. FA degradation proceeds through the β-oxidation cycle that produces acetyl-CoA and reduced NADH and FADH cofactors. In addition to all the enzymes [...] Read more.

Many bacteria possess all the machineries required to grow on fatty acids (FA) as a unique source of carbon and energy. FA degradation proceeds through the β-oxidation cycle that produces acetyl-CoA and reduced NADH and FADH cofactors. In addition to all the enzymes required for β-oxidation, FA degradation also depends on sophisticated systems for its genetic regulation and for FA transport. The fact that these machineries are conserved in bacteria suggests a crucial role in environmental conditions, especially for enterobacteria. Bacteria also possess specific enzymes required for the degradation of FAs from their environment, again showing the importance of this metabolism for bacterial adaptation. In this review, we mainly describe FA degradation in the Escherichia coli model, and along the way, we highlight and discuss important aspects of this metabolism that are still unclear. We do not detail exhaustively the diversity of the machineries found in other bacteria, but we mention them if they bring additional information or enlightenment on specific aspects. Full article

(This article belongs to the Special Issue Theme Issue Honoring Scientist Louis Pasteur on His 200th Birthday)

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10 pages, 1747 KiB

Open AccessReview

Genomic Variation-Mediating Fluconazole Resistance in Yeast

by Wen-Yao Wang, Hong-Qing Cai, Si-Yuan Qu, Wei-Hao Lin, Cheng-Cheng Liang, Hao Liu, Ze-Xiong Xie and Ying-Jin Yuan

Biomolecules 2022, 12(6), 845; https://doi.org/10.3390/biom12060845 - 17 Jun 2022

Cited by 6 | Viewed by 3070

Abstract

Fungal infections pose a serious and growing threat to public health. These infections can be treated with antifungal drugs by killing hazardous fungi in the body. However, the resistance can develop over time when fungi are exposed to antifungal drugs by generating genomic [...] Read more.

Fungal infections pose a serious and growing threat to public health. These infections can be treated with antifungal drugs by killing hazardous fungi in the body. However, the resistance can develop over time when fungi are exposed to antifungal drugs by generating genomic variations, including mutation, aneuploidy, and loss of heterozygosity. The variations could reduce the binding affinity of a drug to its target or block the pathway through which drugs exert their activity. Here, we review genomic variation-mediating fluconazole resistance in the yeast Candida, with the hope of highlighting the functional consequences of genomic variations for the antifungal resistance. Full article

(This article belongs to the Special Issue Theme Issue Honoring Scientist Louis Pasteur on His 200th Birthday)

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22 pages, 3343 KiB

Open AccessReview

Louis Pasteur: Between Myth and Reality

by Jean-Marc Cavaillon and Sandra Legout

Biomolecules 2022, 12(4), 596; https://doi.org/10.3390/biom12040596 - 18 Apr 2022

Cited by 27 | Viewed by 20925

Abstract

Louis Pasteur is the most internationally known French scientist. He discovered molecular chirality, and he contributed to the understanding of the process of fermentation, helping brewers and winemakers to improve their beverages. He proposed a process, known as pasteurization, for the sterilization of [...] Read more.

Louis Pasteur is the most internationally known French scientist. He discovered molecular chirality, and he contributed to the understanding of the process of fermentation, helping brewers and winemakers to improve their beverages. He proposed a process, known as pasteurization, for the sterilization of wines. He established the germ theory of infectious diseases that allowed Joseph Lister to develop his antiseptic practice in surgery. He solved the problem of silkworm disease, although he had refuted the idea of Antoine Béchamp, who first considered it was a microbial infection. He created four vaccines (fowl cholera, anthrax, pig erysipelas, and rabies) in the paths of his precursors, Henri Toussaint (anthrax vaccine) and Pierre Victor Galtier (rabies vaccine). He generalized the word “vaccination” coined by Richard Dunning, Edward Jenner’s friend. Robert Koch, his most famous opponent, pointed out the great ambiguity of Pasteur’s approach to preparing his vaccines. Analysis of his laboratory notebooks has allowed historians to discern the differences between the legend built by his hagiographers and reality. In this review, we revisit his career, his undeniable achievements, and tell the truth about a hero who made every effort to build his own fame. Full article

(This article belongs to the Special Issue Theme Issue Honoring Scientist Louis Pasteur on His 200th Birthday)

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