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Microorganisms
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The Pathogen Streptococcus pneumoniae
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The Pathogen Streptococcus pneumoniae

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

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 19312

Special Issue Editor

Prof. Dr. Regine Hakenbeck

E-Mail Website
Guest Editor
Department of Microbiology, University of Kaiserslautern, Kaiserslautern, Germany
Interests: Streptococcus pneumoniae; pathogenicity; virulence factor; penicillin resistance; genomics cell division; bacterial cell wall; cell surface proteins

Special Issue Information

Dear Colleagues,

Streptococcus pneumoniae is the only major human pathogen among the Mitis group of streptococci. The evolution of this species, its virulence potential, and its amazing ability to become resistant against beta-lactams and other antibiotics within a few decades worldwide have been challenging topics for many years. Due to its potential for genetic transformation, S. pneumoniae genomes bear multiple signs of inter- and intraspecies gene transfer, and thus, closely related streptococci such as S. pseudopneumoniae, S. mitis, and S. oralis are important for evolutionary studies. Meanwhile, it has become clear that pathogenicity is a complex feature controlled by cell surface components, regulatory networks, including those that govern genetic transformation, and genetic interaction with other species. Advances in high-throughput sequencing technologies facilitated the availability of thousands of genome sequences of S. pneumoniae and its relatives, and sophisticated cell biological tools were crucial in unraveling novel aspects on the evolution and the dynamics of cell surface components during the growth cycle of this organism. This volume focuses on recent advances on this fascinating scenario.

Prof. Dr. Regine Hakenbeck
Guest Editor

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Keywords

  • Streptococcus pneumoniae
  • pathogenicity
  • virulence factor
  • penicillin resistance
  • genomics
  • cell division
  • bacterial cell wall
  • cell surface proteins

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Published Papers (5 papers)

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Research

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22 pages, 3101 KiB  
Article
New Insights into Beta-Lactam Resistance of Streptococcus pneumoniae: Serine Protease HtrA Degrades Altered Penicillin-Binding Protein 2x
by Katharina Peters, Inga Schweizer, Regine Hakenbeck and Dalia Denapaite
Microorganisms 2021, 9(8), 1685; https://doi.org/10.3390/microorganisms9081685 - 8 Aug 2021
Cited by 6 | Viewed by 3595
Abstract
Reduced amounts of the essential penicillin-binding protein 2x (PBP2x) were detected in two cefotaxime-resistant Streptococcus pneumoniae laboratory mutants C405 and C606. These mutants contain two or four mutations in the penicillin-binding domain of PBP2x, respectively. The transcription of the pbp2x gene was not [...] Read more.
Reduced amounts of the essential penicillin-binding protein 2x (PBP2x) were detected in two cefotaxime-resistant Streptococcus pneumoniae laboratory mutants C405 and C606. These mutants contain two or four mutations in the penicillin-binding domain of PBP2x, respectively. The transcription of the pbp2x gene was not affected in both mutants; thus, the reduced PBP2x amounts were likely due to post-transcriptional regulation. The mutants carry a mutation in the histidine protein kinase gene ciaH, resulting in enhanced gene expression mediated by the cognate response regulator CiaR. Deletion of htrA, encoding a serine protease regulated by CiaR, or inactivation of HtrA proteolytic activity showed that HtrA is indeed responsible for PBP2x degradation in both mutants, and that this affects β-lactam resistance. Depletion of the PBP2xC405 in different genetic backgrounds confirmed that HtrA degrades PBP2xC405. A GFP-PBP2xC405 fusion protein still localized at the septum in the absence of HtrA. The complementation studies in HtrA deletion strains showed that HtrA can be overexpressed in pneumococcal cells to specific levels, depending on the genetic background. Quantitative Western blotting revealed that the PBP2x amount in C405 strain was less than 20% compared to parental strain, suggesting that PBP2x is an abundant protein in S. pneumoniae R6 strain. Full article
(This article belongs to the Special Issue The Pathogen Streptococcus pneumoniae)
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26 pages, 5741 KiB  
Article
The Two-Component System 09 Regulates Pneumococcal Carbohydrate Metabolism and Capsule Expression
by Stephanie Hirschmann, Alejandro Gómez-Mejia, Ulrike Mäder, Julia Karsunke, Dominik Driesch, Manfred Rohde, Susanne Häussler, Gerhard Burchhardt and Sven Hammerschmidt
Microorganisms 2021, 9(3), 468; https://doi.org/10.3390/microorganisms9030468 - 24 Feb 2021
Cited by 10 | Viewed by 3142
Abstract
Streptococcus pneumoniae two-component regulatory systems (TCSs) are important systems that perceive and respond to various host environmental stimuli. In this study, we have explored the role of TCS09 on gene expression and phenotypic alterations in S. pneumoniae D39. Our comparative transcriptomic analyses identified [...] Read more.
Streptococcus pneumoniae two-component regulatory systems (TCSs) are important systems that perceive and respond to various host environmental stimuli. In this study, we have explored the role of TCS09 on gene expression and phenotypic alterations in S. pneumoniae D39. Our comparative transcriptomic analyses identified 67 differently expressed genes in total. Among those, agaR and the aga operon involved in galactose metabolism showed the highest changes. Intriguingly, the encapsulated and nonencapsulated hk09-mutants showed significant growth defects under nutrient-defined conditions, in particular with galactose as a carbon source. Phenotypic analyses revealed alterations in the morphology of the nonencapsulated hk09- and tcs09-mutants, whereas the encapsulated hk09- and tcs09-mutants produced higher amounts of capsule. Interestingly, the encapsulated D39∆hk09 showed only the opaque colony morphology, while the D39∆rr09- and D39∆tcs09-mutants had a higher proportion of transparent variants. The phenotypic variations of D39ΔcpsΔhk09 and D39ΔcpsΔtcs09 are in accordance with their higher numbers of outer membrane vesicles, higher sensitivity against Triton X-100 induced autolysis, and lower resistance against oxidative stress. In conclusion, these results indicate the importance of TCS09 for pneumococcal metabolic fitness and resistance against oxidative stress by regulating the carbohydrate metabolism and thereby, most likely indirectly, the cell wall integrity and amount of capsular polysaccharide. Full article
(This article belongs to the Special Issue The Pathogen Streptococcus pneumoniae)
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18 pages, 1357 KiB  
Article
Post-Vaccination Streptococcus pneumoniae Carriage and Virulence Gene Distribution among Children Less Than Five Years of Age, Cape Coast, Ghana
by Richael O. Mills, Mohammed R. Abdullah, Samuel A. Akwetey, Dorcas C. Sappor, Isaac Cole, Michael Baffuor-Asare, Johan A. Bolivar, Gustavo Gámez, Mark P. G. van der Linden and Sven Hammerschmidt
Microorganisms 2020, 8(12), 1987; https://doi.org/10.3390/microorganisms8121987 - 13 Dec 2020
Cited by 8 | Viewed by 3767
Abstract
In 2012, Ghana introduced PCV13 into its childhood immunization program. To monitor the pneumococcus after PCV13 vaccination, we analyzed serotypes, antibiotic resistance, and virulence genes of pneumococcal carriage isolates among children under five years of age. We obtained nasopharyngeal swabs from 513 children [...] Read more.
In 2012, Ghana introduced PCV13 into its childhood immunization program. To monitor the pneumococcus after PCV13 vaccination, we analyzed serotypes, antibiotic resistance, and virulence genes of pneumococcal carriage isolates among children under five years of age. We obtained nasopharyngeal swabs from 513 children from kindergartens and immunization centers in Cape Coast, Ghana. Pneumococcal serotypes were determined by multiplex-PCR and Quellung reaction. Antibiotic resistance and virulence genes prevalence were determined by disc diffusion and PCR respectively. Overall, carriage prevalence was 29.4% and PCV13 coverage was 38.4%. Over 60% of the isolates were non-PCV13 serotypes and serotype 23B was the most prevalent. One isolate showed full resistance to penicillin, while 35% showed intermediate resistance. Resistance to erythromycin and clindamycin remained low, while susceptibility to ceftriaxone, levofloxacin and vancomycin remained high. Penicillin resistance was associated with PCV13 serotypes. Forty-three (28.5%) strains were multidrug-resistant. Virulence genes pavB, pcpA, psrP, pilus-1, and pilus-2 were detected in 100%, 87%, 62.9%, 11.9%, and 6.6% of the strains, respectively. The pilus islets were associated with PCV13 and multidrug-resistant serotypes. PCV13 vaccination had impacted on pneumococcal carriage with a significant increase in non-PCV13 serotypes and lower penicillin resistance. Including PcpA and PsrP in pneumococcal protein-based vaccines could be beneficial to Ghanaian children. Full article
(This article belongs to the Special Issue The Pathogen Streptococcus pneumoniae)
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9 pages, 1158 KiB  
Article
Proteomic Adaptation of Streptococcus pneumoniae to the Antimicrobial Peptide Human Beta Defensin 3 (hBD3) in Comparison to Other Cell Surface Stresses
by Pierre-Alexander Mücke, Anne Ostrzinski, Sven Hammerschmidt, Sandra Maaß and Dörte Becher
Microorganisms 2020, 8(11), 1697; https://doi.org/10.3390/microorganisms8111697 - 30 Oct 2020
Cited by 3 | Viewed by 2865
Abstract
The antimicrobial peptide human Beta defensin 3 (hBD3) is an essential part of the innate immune system and is involved in protection against respiratory pathogens by specifically permeabilizing bacterial membranes. The Gram-positive bacterium Streptococcus pneumoniae causes serious diseases including pneumonia, meningitis, and septicemia, [...] Read more.
The antimicrobial peptide human Beta defensin 3 (hBD3) is an essential part of the innate immune system and is involved in protection against respiratory pathogens by specifically permeabilizing bacterial membranes. The Gram-positive bacterium Streptococcus pneumoniae causes serious diseases including pneumonia, meningitis, and septicemia, despite being frequently exposed to human defense molecules, including hBD3 during colonization and infection. Thus, the question arises how pneumococci adapt to stress caused by antimicrobial peptides. We addressed this subject by analyzing the proteome of S. pneumoniae after treatment with hBD3 and compared our data with the proteomic changes induced by LL-37, another crucial antimicrobial peptide present in the human respiratory tract. As antimicrobial peptides usually cause membrane perturbations, the response to the membrane active cationic detergent cetyltrimethylammonium bromide (CTAB) was examined to assess the specificity of the pneumococcal response to antimicrobial peptides. In brief, hBD3 and LL-37 induce a similar response in pneumococci and especially, changes in proteins with annotated transporter and virulence function have been identified. However, LL-37 causes changes in the abundance of cell surface modification proteins that cannot be observed after treatment with hBD3. Interestingly, CTAB induces unique proteomic changes in S. pneumoniae. Though, the detergent seems to activate a two-component system that is also activated in response to antimicrobial peptide stress (TCS 05). Overall, our data represent a novel resource on pneumococcal adaptation to specific cell surface stresses on a functional level. This knowledge can potentially be used to develop strategies to circumvent pneumococcal resistance to antimicrobial peptides. Full article
(This article belongs to the Special Issue The Pathogen Streptococcus pneumoniae)
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Review

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16 pages, 1098 KiB  
Review
Lysogeny in Streptococcus pneumoniae
by Geneviève Garriss and Birgitta Henriques-Normark
Microorganisms 2020, 8(10), 1546; https://doi.org/10.3390/microorganisms8101546 - 7 Oct 2020
Cited by 11 | Viewed by 4945
Abstract
Bacterial viruses, or bacteriophages, are major contributors to the evolution, pathogenesis and overall biology of their host bacteria. During their life cycle, temperate bacteriophages form stable associations with their host by integrating into the chromosome, a process called lysogeny. Isolates of the human [...] Read more.
Bacterial viruses, or bacteriophages, are major contributors to the evolution, pathogenesis and overall biology of their host bacteria. During their life cycle, temperate bacteriophages form stable associations with their host by integrating into the chromosome, a process called lysogeny. Isolates of the human pathogen Streptococcus pneumoniae are frequently lysogenic, and genomic studies have allowed the classification of these phages into distinct phylogenetic groups. Here, we review the recent advances in the characterization of temperate pneumococcal phages, with a focus on their genetic features and chromosomal integration loci. We also discuss the contribution of phages, and specific phage-encoded features, to colonization and virulence. Finally, we discuss interesting research perspectives in this field. Full article
(This article belongs to the Special Issue The Pathogen Streptococcus pneumoniae)
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