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Microorganisms
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Advances in RNA Biology in Pathogenic Microorganisms
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Advances in RNA Biology in Pathogenic Microorganisms

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Molecular Microbiology and Immunology".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 13144

Special Issue Editors

Prof. Rute G. Matos

E-Mail Website
Guest Editor
Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal
Interests: ribonucleases; RNA metabolism; pathogenesis; antimicrobials
Dr. Sandra C. Viegas

E-Mail Website
Co-Guest Editor
Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal
Interests: RNA metabolism; non-coding RNAs; ribonucleases; synthetic biology

Special Issue Information

Dear Colleagues,

In recent years, RNA metabolism has emerged to play crucial roles in the pathogenesis of several microorganisms. We have witnessed an RNA revolution that has forced us to look at this molecule in a different way. This has led to the development of new tools that allow the identification of novel players in RNA metabolism that can be exploited to develop new strategies to fight pathogenic microorganisms.

This Special Issue aims to bring together the latest research that has been developed regarding RNA metabolism in pathogenesis and discuss their potential for the development of new therapeutic applications. We live in an era where microorganisms evolve fast and new outbreaks are being reported, as is the case with the current SARS-CoV-2 pandemic. We need to boost our knowledge on the basic cellular processes involved in pathogenesis in order to develop strategies that can be widely used to tackle pathogenic organisms.

Prof. Rute G. Matos
Guest Editor
Prof. Sandra C. Viegas
Co-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. Microorganisms 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 (5 papers)

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Research

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21 pages, 5020 KiB  
Article
The nsp15 Nuclease as a Good Target to Combat SARS-CoV-2: Mechanism of Action and Its Inactivation with FDA-Approved Drugs
by Margarida Saramago, Vanessa G. Costa, Caio S. Souza, Cátia Bárria, Susana Domingues, Sandra C. Viegas, Diana Lousa, Cláudio M. Soares, Cecília M. Arraiano and Rute G. Matos
Microorganisms 2022, 10(2), 342; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10020342 - 01 Feb 2022
Cited by 11 | Viewed by 2892
Abstract
The pandemic caused by SARS-CoV-2 is not over yet, despite all the efforts from the scientific community. Vaccination is a crucial weapon to fight this virus; however, we still urge the development of antivirals to reduce the severity and progression of the COVID-19 [...] Read more.
The pandemic caused by SARS-CoV-2 is not over yet, despite all the efforts from the scientific community. Vaccination is a crucial weapon to fight this virus; however, we still urge the development of antivirals to reduce the severity and progression of the COVID-19 disease. For that, a deep understanding of the mechanisms involved in viral replication is necessary. nsp15 is an endoribonuclease critical for the degradation of viral polyuridine sequences that activate host immune sensors. This enzyme is known as one of the major interferon antagonists from SARS-CoV-2. In this work, a biochemical characterization of SARS-CoV-2 nsp15 was performed. We saw that nsp15 is active as a hexamer, and zinc can block its activity. The role of conserved residues from SARS-CoV-2 nsp15 was investigated, and N164 was found to be important for protein hexamerization and to contribute to the specificity to degrade uridines. Several chemical groups that impact the activity of this ribonuclease were also identified. Additionally, FDA-approved drugs with the capacity to inhibit the in vitro activity of nsp15 are reported in this work. This study is of utmost importance by adding highly valuable information that can be used for the development and rational design of therapeutic strategies. Full article
(This article belongs to the Special Issue Advances in RNA Biology in Pathogenic Microorganisms)
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15 pages, 1891 KiB  
Article
RNase R, a New Virulence Determinant of Streptococcus pneumoniae
by Cátia Bárria, Dalila Mil-Homens, Sandra N. Pinto, Arsénio M. Fialho, Cecília M. Arraiano and Susana Domingues
Microorganisms 2022, 10(2), 317; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10020317 - 29 Jan 2022
Cited by 3 | Viewed by 2343
Abstract
Pneumococcal infections have increasingly high mortality rates despite the availability of vaccines and antibiotics. Therefore, the identification of new virulence determinants and the understanding of the molecular mechanisms behind pathogenesis have become of paramount importance in the search of new targets for drug [...] Read more.
Pneumococcal infections have increasingly high mortality rates despite the availability of vaccines and antibiotics. Therefore, the identification of new virulence determinants and the understanding of the molecular mechanisms behind pathogenesis have become of paramount importance in the search of new targets for drug development. The exoribonuclease RNase R has been involved in virulence in a growing number of pathogens. In this work, we used Galleria mellonella as an infection model to demonstrate that the presence of RNase R increases the pneumococcus virulence. Larvae infected with the RNase R mutant show an increased expression level of antimicrobial peptides. Furthermore, they have a lower bacterial load in the hemolymph in the later stages of infection, leading to a higher survival rate of the larvae. Interestingly, pneumococci expressing RNase R show a sudden drop in bacterial numbers immediately after infection, resembling the eclipse phase observed after intravenous inoculation in mice. Concomitantly, we observed a lower number of mutant bacteria inside larval hemocytes and a higher susceptibility to oxidative stress when compared to the wild type. Together, our results indicate that RNase R is involved in the ability of pneumococci to evade the host immune response, probably by interfering with internalization and/or replication inside the larval hemocytes. Full article
(This article belongs to the Special Issue Advances in RNA Biology in Pathogenic Microorganisms)
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8 pages, 1277 KiB  
Communication
Novel RNA Extraction Method for Dual RNA-seq Analysis of Pathogen and Host in the Early Stages of Yersinia pestis Pulmonary Infection
by Ofir Israeli, Inbar Cohen-Gihon, Moshe Aftalion, David Gur, Yaron Vagima, Ayelet Zauberman, Yinon Levy, Anat Zvi, Theodor Chitlaru, Emanuelle Mamroud and Avital Tidhar
Microorganisms 2021, 9(10), 2166; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9102166 - 18 Oct 2021
Cited by 1 | Viewed by 2005
Abstract
Pneumonic plague, caused by Yersinia pestis, is a rapidly progressing lethal infection. The various phases of pneumonic plague are yet to be fully understood. A well-established way to address the pathology of infectious diseases in general, and pneumonic plague in particular, is to [...] Read more.
Pneumonic plague, caused by Yersinia pestis, is a rapidly progressing lethal infection. The various phases of pneumonic plague are yet to be fully understood. A well-established way to address the pathology of infectious diseases in general, and pneumonic plague in particular, is to conduct concomitant transcriptomic analysis of the bacteria and the host. The analysis of dual RNA by RNA sequencing technology is challenging, due the difficulties of extracting bacterial RNA, which is overwhelmingly outnumbered by the host RNA, especially at the critical early time points post-infection (prior to 48 h). Here, we describe a novel technique that employed the infusion of an RNA preserving reagent (RNAlater) into the lungs of the animals, through the trachea, under deep anesthesia. This method enabled the isolation of stable dual mRNA from the lungs of mice infected with Y. pestis, as early as 24 h post-infection. The RNA was used for transcriptomic analysis, which provided a comprehensive gene expression profile of both the host and the pathogen. Full article
(This article belongs to the Special Issue Advances in RNA Biology in Pathogenic Microorganisms)
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21 pages, 3053 KiB  
Article
A Small Non-Coding RNA Modulates Expression of Pilus-1 Type in Streptococcus pneumoniae
by Paloma Acebo, Cristina Herranz, Lucas Bernal Espenberger, Alicia Gómez-Sanz, María Carmen Terrón, Daniel Luque and Mónica Amblar
Microorganisms 2021, 9(9), 1883; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9091883 - 05 Sep 2021
Cited by 3 | Viewed by 2197
Abstract
Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide, and about 30% of the pneumococcal clinical isolates show type I pili-like structures. These long proteinaceous polymers extending from the bacterial surface are encoded by pilus islet 1 and play major roles [...] Read more.
Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide, and about 30% of the pneumococcal clinical isolates show type I pili-like structures. These long proteinaceous polymers extending from the bacterial surface are encoded by pilus islet 1 and play major roles in adhesion and host colonization. Pili expression is bistable and is controlled by the transcriptional activator RlrA. In this work, we demonstrate that the previously identified small noncoding RNA srn135 also participates in pilus regulation. Our findings show that srn135 is generated upon processing of the 5′-UTR region of rrgA messenger and its deletion prevents the synthesis of RrgA, the main pili adhesin. Moreover, overexpression of srn135 increases the expression of all pili genes and rises the percentage of piliated bacteria within a clonal population. This regulation is mediated by the stabilization of rlrA mRNA since higher levels of srn135 increase its half-life to 165%. Our findings suggest that srn135 has a dual role in pilus expression acting both in cis- (on the RrgA levels) and in trans- (modulating the levels of RlrA) and contributes to the delicate balance between pili expressing and non-expressing bacteria. Full article
(This article belongs to the Special Issue Advances in RNA Biology in Pathogenic Microorganisms)
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Review

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31 pages, 4058 KiB  
Review
Developing New Tools to Fight Human Pathogens: A Journey through the Advances in RNA Technologies
by Vanessa G. Costa, Susana M. Costa, Margarida Saramago, Marta V. Cunha, Cecília M. Arraiano, Sandra C. Viegas and Rute G. Matos
Microorganisms 2022, 10(11), 2303; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10112303 - 21 Nov 2022
Cited by 1 | Viewed by 2619
Abstract
A long scientific journey has led to prominent technological advances in the RNA field, and several new types of molecules have been discovered, from non-coding RNAs (ncRNAs) to riboswitches, small interfering RNAs (siRNAs) and CRISPR systems. Such findings, together with the recognition of [...] Read more.
A long scientific journey has led to prominent technological advances in the RNA field, and several new types of molecules have been discovered, from non-coding RNAs (ncRNAs) to riboswitches, small interfering RNAs (siRNAs) and CRISPR systems. Such findings, together with the recognition of the advantages of RNA in terms of its functional performance, have attracted the attention of synthetic biologists to create potent RNA-based tools for biotechnological and medical applications. In this review, we have gathered the knowledge on the connection between RNA metabolism and pathogenesis in Gram-positive and Gram-negative bacteria. We further discuss how RNA techniques have contributed to the building of this knowledge and the development of new tools in synthetic biology for the diagnosis and treatment of diseases caused by pathogenic microorganisms. Infectious diseases are still a world-leading cause of death and morbidity, and RNA-based therapeutics have arisen as an alternative way to achieve success. There are still obstacles to overcome in its application, but much progress has been made in a fast and effective manner, paving the way for the solid establishment of RNA-based therapies in the future. Full article
(This article belongs to the Special Issue Advances in RNA Biology in Pathogenic Microorganisms)
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