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Pathogens
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Streptococcus pneumoniae
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Streptococcus pneumoniae

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Bacterial Pathogens".

Deadline for manuscript submissions: closed (15 November 2021) | Viewed by 15070

Special Issue Editors

Dr. Bindu Nanduri

E-Mail Website
Guest Editor
College of Veterinary Medicine, Mississippi State University
Interests: polyamine metabolism; capsule; stress responses; bioinformatics; functional genomics
Dr. Ed Swiatlo

E-Mail Website
Co-Guest Editor
Medical Service, Section of Infectious, Diseases VA Medical Center
Interests: Streptococcus pneumoniae vaccines, pathogenesis of pneumococcal infections, polyamines in S. pneumoniae, opportunistic infections in HIV

Special Issue Information

Dear Colleagues,

Respiratory infections continue to be a significant cause of global mortality and consume a large portion of health-care resources in both developed and developing countries. Most reports identify Streptococcus pneumoniae (pneumococcus) as one of the most common and important bacterial etiologies of respiratory infections. For over one hundred years, intensive research efforts have been directed to prevention and treatment of pneumococcal disease. Pneumococci normally inhabit the upper respiratory tract as commensals, but when translocated to the lungs, blood, or central nervous system they can adapt and survive in these varying host environments. Adaption to these different environments and stressors requires agile control of gene expression at a global level, which affects not just classical virulence factors but also a variety of metabolic pathways. The role of central metabolism in pneumococcal pathogenesis continues to unfold. There are currently several widely utilized vaccines based on capsular polysaccharides, an immunodominant and protective antigen found on nearly all virulent pneumococci. However, the vast number of distinct capsule serotypes and the genetic plasticity of pneumococci strongly portends that this preventive strategy will not be adequate to ultimately control the global burden of disease. Immunization strategies based on antigens conserved across multiple capsular types promise to expand coverage for all populations and further reduce disease burden. A number of proteins have been identified which may potentially elicit protective immune responses and are effective in animal models of pneumococcal infection. This Special Issue will collect the latest information on pneumococcal immunology, virulence, and metabolism to demonstrate the underlying relationships among these aspects of pneumococcal pathogenesis. Investigators who are actively working in these fields are encouraged to share their findings and insights so that we may collectively identify a way forward to advance the treatment and prevention of pneumococcal disease.

Dr. Bindu Nanduri
Guest Editor
Dr. Ed Swiatlo
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. 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 2200 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.

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 2200 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.

Keywords

  • Streptococcus pneumoniae vaccines
  • pathogenesis of pneumococcal infections
  • polyamines in S. pneumoniae
  • opportunistic infections in HIV
  • metals
  • transporters
  • metabolomics
  • host-pathogen interactions
  • stress responses
  • genetics
  • genomics

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Published Papers (6 papers)

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Research

12 pages, 1757 KiB  
Article
The Role of luxS in the Middle Ear Streptococcus pneumoniae Isolate 947
by Alexandra Tikhomirova, Erin B. Brazel, Kimberley T. McLean, Hannah N. Agnew, James C. Paton and Claudia Trappetti
Pathogens 2022, 11(2), 216; https://doi.org/10.3390/pathogens11020216 - 7 Feb 2022
Cited by 2 | Viewed by 1624
Abstract
The LuxS protein, encoded by luxS, is required for the production of autoinducer 2 (AI-2) in Streptococcus pneumoniae. The AI-2 molecule serves as a quorum sensing signal, and thus regulates cellular processes such as carbohydrate utilisation and biofilm formation, as well [...] Read more.
The LuxS protein, encoded by luxS, is required for the production of autoinducer 2 (AI-2) in Streptococcus pneumoniae. The AI-2 molecule serves as a quorum sensing signal, and thus regulates cellular processes such as carbohydrate utilisation and biofilm formation, as well as impacting virulence. The role of luxS in S. pneumoniae biology and lifestyle has been predominantly assessed in the laboratory strain D39. However, as biofilm formation, which is regulated by luxS, is critical for the ability of S. pneumoniae to cause otitis media, we investigated the role of luxS in a middle ear isolate, strain 947. Our results identified luxS to have a role in prevention of S. pneumoniae transition from colonisation of the nasopharynx to the ear, and in facilitating adherence to host epithelial cells. Full article
(This article belongs to the Special Issue Streptococcus pneumoniae)
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10 pages, 3431 KiB  
Communication
Extracellular Vesicles from Different Pneumococcal Serotypes Are Internalized by Macrophages and Induce Host Immune Responses
by Alfonso Olaya-Abril, Rafael Prados-Rosales, José A. González-Reyes, Arturo Casadevall, Liise-anne Pirofski and Manuel J. Rodríguez-Ortega
Pathogens 2021, 10(12), 1530; https://doi.org/10.3390/pathogens10121530 - 23 Nov 2021
Cited by 7 | Viewed by 2180
Abstract
Bacterial extracellular vesicles are membranous ultrastructures released from the cell surface. They play important roles in the interaction between the host and the bacteria. In this work, we show how extracellular vesicles produced by four different serotypes of the important human pathogen, Streptococcus [...] Read more.
Bacterial extracellular vesicles are membranous ultrastructures released from the cell surface. They play important roles in the interaction between the host and the bacteria. In this work, we show how extracellular vesicles produced by four different serotypes of the important human pathogen, Streptococcus pneumoniae, are internalized by murine J774A.1 macrophages via fusion with the membrane of the host cells. We also evaluated the capacity of pneumococcal extracellular vesicles to elicit an immune response by macrophages. Macrophages treated with the vesicles underwent a serotype-dependent transient loss of viability, which was further reverted. The vesicles induced the production of proinflammatory cytokines, which was higher for serotype 1 and serotype 8-derived vesicles. These results demonstrate the biological activity of extracellular vesicles of clinically important pneumococcal serotypes. Full article
(This article belongs to the Special Issue Streptococcus pneumoniae)
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18 pages, 1776 KiB  
Article
The Effect of Impaired Polyamine Transport on Pneumococcal Transcriptome
by Mary F. Nakamya, Moses B. Ayoola, Leslie A. Shack, Edwin Swiatlo and Bindu Nanduri
Pathogens 2021, 10(10), 1322; https://doi.org/10.3390/pathogens10101322 - 14 Oct 2021
Cited by 5 | Viewed by 2041
Abstract
Infections due to Streptococcus pneumoniae, a commensal in the nasopharynx, still claim a significant number of lives worldwide. Genome plasticity, antibiotic resistance, and limited serotype coverage of the available polysaccharide-based conjugate vaccines confounds therapeutic interventions to limit the spread of this pathogen. [...] Read more.
Infections due to Streptococcus pneumoniae, a commensal in the nasopharynx, still claim a significant number of lives worldwide. Genome plasticity, antibiotic resistance, and limited serotype coverage of the available polysaccharide-based conjugate vaccines confounds therapeutic interventions to limit the spread of this pathogen. Pathogenic mechanisms that allow successful adaption and persistence in the host could be potential innovative therapeutic targets. Polyamines are ubiquitous polycationic molecules that regulate many cellular processes. We previously reported that deletion of polyamine transport operon potABCD, which encodes a putrescine/spermidine transporter (ΔpotABCD), resulted in an unencapsulated attenuated phenotype. Here, we characterize the transcriptome, metabolome, and stress responses of polyamine transport-deficient S. pneumoniae. Compared with the wild-type strain, the expression of genes involved in oxidative stress responses and the nucleotide sugar metabolism was reduced, while expression of genes involved in the Leloir, tagatose, and pentose phosphate pathways was higher in ΔpotABCD. A metabolic shift towards the pentose phosphate pathway will limit the synthesis of precursors of capsule polysaccharides. Metabolomics results show reduced levels of glutathione and pyruvate in the mutant. Our results also show that the potABCD operon protects pneumococci against hydrogen peroxide and nitrosative stress. Our findings demonstrate the importance of polyamine transport in pneumococcal physiology that could impact in vivo fitness. Thus, polyamine transport in pneumococci represents a novel target for therapeutic interventions. Full article
(This article belongs to the Special Issue Streptococcus pneumoniae)
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13 pages, 1498 KiB  
Article
Approaching In Vivo Models of Pneumococcus–Host Interaction: Insights into Surface Proteins, Capsule Production, and Extracellular Vesicles
by Alfonso Olaya-Abril, José A. González-Reyes and Manuel J. Rodríguez-Ortega
Pathogens 2021, 10(9), 1098; https://doi.org/10.3390/pathogens10091098 - 28 Aug 2021
Cited by 5 | Viewed by 2958
Abstract
Infections caused by the Gram-positive bacterium Streptococcus pneumoniae have become a major health problem worldwide because of their high morbidity and mortality rates, especially in developing countries. This microorganism colonizes the human upper respiratory tract and becomes pathogenic under certain circumstances, which are [...] Read more.
Infections caused by the Gram-positive bacterium Streptococcus pneumoniae have become a major health problem worldwide because of their high morbidity and mortality rates, especially in developing countries. This microorganism colonizes the human upper respiratory tract and becomes pathogenic under certain circumstances, which are not well known. In the interaction with the host, bacterial surface structures and proteins play major roles. To gain knowledge into gradual changes and adaptive mechanisms that this pathogen undergoes from when it enters the host, we mimicked several in vivo situations representing interaction with epithelial and macrophage cells, as well as a condition of presence in blood. Then, we analyzed, in four pneumococcal strains, two major surface structures, the capsule and extracellular vesicles produced by the pneumococci, as well as surface proteins by proteomics, using the “shaving” approach, followed by LC-MS/MS. We found important differences in both surface ultrastructures and proteins among the culture conditions and strains used. Thus, this work provides insights into physiological adaptations of the pneumococcus when it interacts with the host, which may be useful for the design of strategies to combat infections caused by this pathogen. Full article
(This article belongs to the Special Issue Streptococcus pneumoniae)
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13 pages, 1756 KiB  
Article
Arginine Decarboxylase Is Essential for Pneumococcal Stress Responses
by Mary Frances Nakamya, Moses B. Ayoola, Leslie A. Shack, Mirghani Mohamed, Edwin Swiatlo and Bindu Nanduri
Pathogens 2021, 10(3), 286; https://doi.org/10.3390/pathogens10030286 - 2 Mar 2021
Cited by 6 | Viewed by 2129
Abstract
Polyamines such as putrescine, cadaverine, and spermidine are small cationic molecules that play significant roles in cellular processes, including bacterial stress responses and host–pathogen interactions. Streptococcus pneumoniae is an opportunistic human pathogen, which causes several diseases that account for significant morbidity and mortality [...] Read more.
Polyamines such as putrescine, cadaverine, and spermidine are small cationic molecules that play significant roles in cellular processes, including bacterial stress responses and host–pathogen interactions. Streptococcus pneumoniae is an opportunistic human pathogen, which causes several diseases that account for significant morbidity and mortality worldwide. As it transits through different host niches, S. pneumoniae is exposed to and must adapt to different types of stress in the host microenvironment. We earlier reported that S. pneumoniae TIGR4, which harbors an isogenic deletion of an arginine decarboxylase (ΔspeA), an enzyme that catalyzes the synthesis of agmatine in the polyamine synthesis pathway, has a reduced capsule. Here, we report the impact of arginine decarboxylase deletion on pneumococcal stress responses. Our results show that ΔspeA is more susceptible to oxidative, nitrosative, and acid stress compared to the wild-type strain. Gene expression analysis by qRT-PCR indicates that thiol peroxidase, a scavenger of reactive oxygen species and aguA from the arginine deiminase system, could be important for peroxide stress responses in a polyamine-dependent manner. Our results also show that speA is essential for endogenous hydrogen peroxide and glutathione production in S. pneumoniae. Taken together, our findings demonstrate the critical role of arginine decarboxylase in pneumococcal stress responses that could impact adaptation and survival in the host. Full article
(This article belongs to the Special Issue Streptococcus pneumoniae)
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14 pages, 2257 KiB  
Article
Comparative Analysis of Streptococcus pneumoniae Type I Restriction-Modification Loci: Variation in hsdS Gene Target Recognition Domains
by Melissa B. Oliver and W. Edward Swords
Pathogens 2020, 9(9), 712; https://doi.org/10.3390/pathogens9090712 - 29 Aug 2020
Cited by 5 | Viewed by 3054
Abstract
Streptococcus pneumoniae (pneumococcus) is a respiratory commensal pathogen that causes a range of infections, particularly in young children and the elderly. Pneumococci undergo spontaneous phase variation in colony opacity phenotype, in which DNA rearrangements within the Type I restriction-modification (R-M) system specificity gene [...] Read more.
Streptococcus pneumoniae (pneumococcus) is a respiratory commensal pathogen that causes a range of infections, particularly in young children and the elderly. Pneumococci undergo spontaneous phase variation in colony opacity phenotype, in which DNA rearrangements within the Type I restriction-modification (R-M) system specificity gene hsdS can potentially generate up to six different hsdS alleles with differential DNA methylation activity, resulting in changes in gene expression. To gain a broader perspective of this system, we performed bioinformatic analyses of Type I R-M loci from 18 published pneumococcal genomes, and one R-M locus sequenced for this study, to compare genetic content, organization, and homology. All 19 loci encoded the genes hsdR, hsdM, hsdS, and at least one hsdS pseudogene, but differed in gene order, gene orientation, and hsdS target recognition domain (TRD) content. We determined the coding sequences of 87 hsdS TRDs and excluded seven from further analysis due to the presence of premature stop codons. Comparative analyses revealed that the TRD 1.1, 1.2, and 2.1 protein sequences had single amino acid substitutions, and TRD 2.2 and 2.3 each had seven differences. The results of this study indicate that variability exists among the gene content and arrangements within Type I R-M loci may provide an additional level of divergence between pneumococcal strains, such that phase variation-mediated control of virulence factors may vary significantly between individual strains. These findings are consistent with presently available transcript profile data. Full article
(This article belongs to the Special Issue Streptococcus pneumoniae)
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