Pneumococcal Metabolic Adaptation and Colonization Are Regulated by the Two-Component Regulatory System 08

Gómez-Mejía, Alejandro; Gámez, Gustavo; Hirschmann, Stephanie; Kluger, Viktor; Rath, Hermann; Böhm, Sebastian; Voß, Franziska; Kakar, Niamatullah; Petruschka, Lothar; Völker, Uwe; Brückner, Reinhold; Mäder, Ulrike; Hammerschmidt, Sven

doi:10.1128/msphere.00165-18

Cited by 16 publications

(20 citation statements)

References 60 publications

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“…We have shown previously that TCS08 is involved in pneumococcal colonization by regulating the virulence factors PavB, the rlrA islet (Pilus-1), and the cellobiose metabolism. Moreover, the TCS08 effect on regulatory processes including colonization is strain-dependent, as shown in a murine model when comparing S. pneumoniae strains TIGR4 and D39 [7]. Recently, TCS01 (SirRH) was shown to increase pneumococcal survival in pneumocytes after influenza An infection by transcription of genes involved stress response [6].…”

Section: Introductionmentioning

confidence: 95%

“…Pneumococcal ∆rr09 (spd_0574; SPD_RS03105), ∆hk09 (spd_0575; SPD_RS03110), and ∆tcs09, lacking the rr09 and hk09 mutants, were constructed by insertion-deletion mutagenesis ( Figure S1). Transformation of S. pneumoniae D39 using the constructed plasmids was performed in the presence of competence-stimulating peptide CSP1, as described [7]. Transformants were selected on blood agar plates containing 5 µg/mL erythromycin, and all mutants were confirmed on the molecular level by colony PCR and RNA-sequencing.…”

Section: Generation Of Pneumococcal Mutantsmentioning

confidence: 99%

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The Two-Component System 09 Regulates Pneumococcal Carbohydrate Metabolism and Capsule Expression

et al. 2021

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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.

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Section: Introductionmentioning

confidence: 95%

Section: Generation Of Pneumococcal Mutantsmentioning

confidence: 99%

The Two-Component System 09 Regulates Pneumococcal Carbohydrate Metabolism and Capsule Expression

et al. 2021

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“…In addition to specific control mechanisms focused on proper P1 biosynthesis, signals from general regulatory networks of the complex interplay between S. pneumoniae and the human host are supposed to influence P1 expression ( Kreikemeyer et al, 2011 ; Gómez-Mejia et al, 2018 ). Transcriptional P1 regulation seems to be of major importance: besides a suggested negative regulation by RrgA ( Basset et al, 2011 ), PI-1 was described to be positively controlled by a RlrA feedback loop ( Basset et al, 2012 ).…”

Section: Subunits and Sortase-mediated Assembly Of Pneumococcal Pilusmentioning

confidence: 99%

Streptococcus pneumoniae Type 1 Pilus – A Multifunctional Tool for Optimized Host Interaction

Ness

Hilleringmann

2021

Front. Microbiol.

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Streptococcus pneumoniae represents a major Gram-positive human pathogen causing bacterial pneumonia, otitis media, meningitis, and other invasive diseases. Several pneumococcal isolates show increasing resistance rates against antibacterial agents. A variety of virulence factors promote pneumococcal pathogenicity with varying importance in different stages of host infection. Virulence related hair-like structures (“pili”) are complex, surface located protein arrays supporting proper host interaction. In the last two decades different types of pneumococcal pili have been identified: pilus-1 (P1) and pilus-2 (P2) are formed by the catalytic activity of sortases that covalently assemble secreted polypeptide pilin subunits in a defined order and finally anchor the resulting pilus in the peptidoglycan. Within the long pilus fiber the presence of intramolecular isopeptide bonds confer high stability to the sequentially arranged individual pilins. This mini review will focus on S. pneumoniae TIGR4 P1 molecular architecture, the subunits it builds and provides insights into P1 sortase-mediated assembly. The complex P1 architecture (anchor-/backbone-/tip-subunits) allows the specific interaction with various target structures facilitating different steps of colonization, invasion and spreading within the host. Optimized pilin subunit confirmation supports P1 function under physiological conditions. Finally, aspects of P1- host interplay are summarized, including recent insights into P1 mechanobiology, which have important implications for P1 mediated pathogenesis.

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“…Differential expression of pneumococcal genes between serotypes 1 ST217 and 2 D39. The gene expression profile of bacterial pathogens during in vitro growth can reflect their pathogenic lifestyle; invasive variants of S. pneumoniae have been reported to express higher levels of invasion-associated genes than noninvasive variants (23)(24)(25)(26). Therefore, we compared the in vitro expression pattern of genes known to be involved in (i) the metabolism of carbohydrates, (ii) intraspecies competition, and (iii) virulence in serotype 1 ST217 strain and the serotype 2 (D39) strain.…”

Section: Resultsmentioning

confidence: 99%

Lower Density and Shorter Duration of Nasopharyngeal Carriage by Pneumococcal Serotype 1 (ST217) May Explain Its Increased Invasiveness over Other Serotypes

Bricio-Moreno

Chaguza

Yahya

et al. 2020

mBio

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Streptococcus pneumoniae is a frequent colonizer of the human nasopharynx and a major cause of life-threating invasive infections such as pneumonia, meningitis and sepsis. Over 1 million people die every year due to invasive pneumococcal disease (IPD), mainly in developing countries. Serotype 1 is a common cause of IPD; however, unlike other serotypes, it is rarely found in the carrier state in the nasopharynx, which is often considered a prerequisite for disease. The aim of this study was to understand this dichotomy. We used murine models of carriage and IPD to characterize the pathogenesis of African serotype 1 (sequence type 217) pneumococcal strains obtained from the Queen Elizabeth Central Hospital in Blantyre, Malawi. We found that ST217 pneumococcal strains were highly virulent in a mouse model of invasive pneumonia, but in contrast to the generally accepted assumption, can also successfully establish nasopharyngeal carriage. Interestingly, we found that cocolonizing serotypes may proliferate in the presence of serotype 1, suggesting that acquisition of serotype 1 carriage could increase the risk of developing IPD by other serotypes. RNA sequencing analysis confirmed that key virulence genes associated with inflammation and tissue invasiveness were upregulated in serotype 1. These data reveal important new insights into serotype 1 pathogenesis, with implications for carriage potential and risk of invasive disease through interactions with other cocolonizing serotypes, an often-overlooked factor in transmission and disease progression. IMPORTANCE The pneumococcus causes serious diseases such as pneumonia, sepsis, and meningitis and is a major cause of morbidity and mortality worldwide. Serotype 1 accounts for the majority of invasive pneumococcal disease cases in sub-Saharan Africa but is rarely found during nasopharyngeal carriage. Understanding the mechanisms leading to nasopharyngeal carriage and invasive disease by this serotype can help reduce its burden on health care systems worldwide. In this study, we also uncovered the potential impact of serotype 1 on disease progression of other coinfecting serotypes, which can have important implications for vaccine efficacy. Understanding the interactions between different serotypes during nasopharyngeal carriage may lead to improved intervention methods and therapies to reduce pneumococcal invasive disease levels.

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Pneumococcal Metabolic Adaptation and Colonization Are Regulated by the Two-Component Regulatory System 08

Cited by 16 publications

References 60 publications

The Two-Component System 09 Regulates Pneumococcal Carbohydrate Metabolism and Capsule Expression

The Two-Component System 09 Regulates Pneumococcal Carbohydrate Metabolism and Capsule Expression

Streptococcus pneumoniae Type 1 Pilus – A Multifunctional Tool for Optimized Host Interaction

Lower Density and Shorter Duration of Nasopharyngeal Carriage by Pneumococcal Serotype 1 (ST217) May Explain Its Increased Invasiveness over Other Serotypes

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