The virulence of Streptococcus pneumoniae partially depends on dprA

Yu, Yi; Chang, Dan; Xu, Huiwen; Zhang, Xuelin; Pan, Lei; Xu, Chou; Huang, Bing; Zhou, Hong; Li, Jia; Guo, Jun; Liu, Changting

doi:10.1016/j.bjm.2016.10.019

Cited by 10 publications

(9 citation statements)

References 26 publications

(31 reference statements)

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“…As previously shown by us and others, the ΔdprA mutant is attenuated in mouse models of infection (25,28). When competed against the WT, the ΔdprA mutant was less competitive in bacteremia, acute-pneumonia infections, and nasopharyngeal colonization (Fig.…”

Section: Resultssupporting

confidence: 64%

DprA-Dependent Exit from the Competent State Regulates Multifaceted Streptococcus pneumoniae Virulence

Lin

Lau

2019

Infect Immun

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Streptococcus pneumoniae (pneumococcus) causes multiple infectious diseases. The pneumococcal competence system facilitates genetic transformation, spreads antibiotic resistance, and contributes to virulence. DNA-processing protein A (DprA) regulates the exit of pneumococcus from the competent state. Previously, we have shown that DprA is important in both bacteremia and pneumonia infections. Here, we examined the mechanisms of virulence attenuation in a ΔdprA mutant. Compared to the parental wild-type D39, the ΔdprA mutant enters the competent state when exposed to lower concentrations of the competence-stimulating peptide CSP1. The ΔdprA mutant overexpresses ComM, which delays cell separation after division. Additionally, the ΔdprA mutant overexpresses allolytic factors LytA, CbpD, and CibAB and is more susceptible to detergent-triggered lysis. Disabling of the competent-state-specific induction of ComM and allolytic factors compensated for the virulence loss in the ΔdprA mutant, suggesting that overexpression of these factors contributes to virulence attenuation. Finally, the ΔdprA mutant fails to downregulate the expression of multiple competence-regulated genes, leading to the excessive energy consumption. Collectively, these results indicate that an inability to properly exit the competent state disrupts multiple cellular processes that cause virulence attenuation in the ΔdprA mutant.

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Section: Resultssupporting

confidence: 64%

DprA-Dependent Exit from the Competent State Regulates Multifaceted Streptococcus pneumoniae Virulence

Lin

Lau

2019

Infect Immun

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“…Adhesion and intracellular invasion capabilities were measured according to methods in a previous report ( Yu et al, 2017 ). A549 cells were cultured in DMEM (Thermo Fisher Scientific, United States) with 10% fetal bovine serum (FBS; Thermo Fisher Scientific, United States) at 37°C in 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

A Novel Iron Transporter SPD_1590 in Streptococcus pneumoniae Contributing to Bacterial Virulence Properties

Miao

Zhang

et al. 2018

Front. Microbiol.

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Streptococcus pneumoniae, a Gram-positive human pathogen, has evolved three main transporters for iron acquisition from the host: PiaABC, PiuABC, and PitABC. Our previous study had shown that the mRNA and protein levels of SPD_1590 are significantly upregulated in the ΔpiuA/ΔpiaA/ΔpitA triple mutant, suggesting that SPD_1590 might be a novel iron transporter in S. pneumoniae. In the present study, using spd1590-knockout, -complemented, and -overexpressing strains and the purified SPD_1590 protein, we show that SPD_1590 can bind hemin, probably supplementing the function of PiuABC, to provide the iron necessary for the bacterium. Furthermore, the results of iTRAQ quantitative proteomics and cell-infection studies demonstrate that, similarly to other metal-ion uptake proteins, SPD_1590 is important for bacterial virulence properties. Overall, these results provide a better understanding of the biology of this clinically important bacterium.

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“…) was a composite parameter of the literature derived growth rate of D39 (38) and our experimental growth rate ratio between mutant and WT. The systems growth capacity limitation parameter (B max ) and the bacterial concentration at the start of the infection were obtained from an in vivo model of bacteraemia (39).…”

Section: ீ mentioning

confidence: 99%

Allele-specific collateral and fitness effects determine the dynamics of fluoroquinolone-resistance evolution

Liakopoulos

Aulin

Buffoni

et al. 2020

Preprint

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Collateral sensitivity (CS), which arises when resistance to one antibiotic increases sensitivity towards other antibiotics, offers novel treatment opportunities to constrain or reverse the evolution of antibiotic resistance. The applicability of CS-informed treatments remains uncertain, in part because we lack an understanding of the generality of CS effects for different resistance mutations, singly or in combination. Here we address this issue in the Gram-positive pathogen S. pneumoniae by quantifying collateral and fitness effects of a series of clinically relevant first-step (gyrA or parC) mutations, and their combinations, that confer resistance to fluoroquinolones. We integrated these results in a mathematical model which allowed us to evaluate how different in silico combination treatments impact the dynamics of resistance evolution. We identified common and conserved CS effects of different gyrA and parC mutations; however, the spectrum of collateral effects was unique for each mutation or mutation pair. This indicated that mutation identity, even different mutations to the same amino acid, can impact the evolutionary dynamics of resistance evolution during monotreatment and combination treatment. In addition, we observed that epistatic effects between gyrA and parC mutations strongly alter the strength of collateral effects against different antibiotics. Our model simulations, which included the experimentally derived antibiotic susceptibilities and fitness effects, and antibiotic specific pharmacodynamics, revealed that both collateral and fitness effects impact the population dynamics of resistance evolution. Overall, we provide evidence that the gene, mutational identity, and interactions between resistance mutations can have a pronounced impact on collateral effects to different antibiotics and suggest that these need to be considered in models examining CS-based therapies.

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The virulence of Streptococcus pneumoniae partially depends on dprA

Cited by 10 publications

References 26 publications

DprA-Dependent Exit from the Competent State Regulates Multifaceted Streptococcus pneumoniae Virulence

DprA-Dependent Exit from the Competent State Regulates Multifaceted Streptococcus pneumoniae Virulence

A Novel Iron Transporter SPD_1590 in Streptococcus pneumoniae Contributing to Bacterial Virulence Properties

Allele-specific collateral and fitness effects determine the dynamics of fluoroquinolone-resistance evolution

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