Transcriptional regulation of TacL-mediated lipoteichoic acids biosynthesis by ComE during competence impacts pneumococcal transformation.

Competence development is essential for bacterial transformation since it enables bacteria to take up free DNA from the surrounding environment. The regulation of teichoic acid biosynthesis is tightly controlled during pneumococcal competence; however, the mechanism governing this regulation and its impact on transformation remains poorly understood. We demonstrated that a defect in lipoteichoic acid ligase (TacL)-mediated lipoteichoic acids (LTAs) biosynthesis was associated with impaired pneumococcal transformation. Using a fragment of tacL regulatory probe as bait in a DNA pulldown assay, we successfully identified several regulatory proteins, including ComE. Electrophoretic mobility shift assays revealed that phosphomimetic ComE, but not wild-type ComE, exhibited specific binding to the probe. DNase I footprinting assays revealed the specific binding sequences encompassing around 30 base pairs located 31 base pairs upstream from the start codon of tacL. Expression of tacL was found to be upregulated in the ΔcomE strain, and the addition of exogenous competence-stimulating peptide repressed the tacL transcription in the wild-type strain but not the ΔcomE mutant, indicating that ComE exerted a negative regulatory effect on the transcription of tacL. Mutation in the JH2 region of tacL upstream regulatory sequence led to increased LTAs abundance and displayed higher transformation efficiency. Collectively, our work identified the regulatory mechanisms that control LTAs biosynthesis during competence and thereby unveiled a repression mechanism underlying pneumococcal transformation.

comCDE (Competence) Operon Is Regulated by CcpA in Streptococcus pneumoniae D39.

Natural transformation plays an important role in the formation of drug-resistant bacteria. Exploring the regulatory mechanism of natural transformation can aid the discovery of new antibacterial targets and reduce the emergence of drug-resistant bacteria. Competence is a prerequisite of natural transformation in Streptococcus pneumoniae, in which comCDE operon is the core regulator of competence. To date, only ComE has been shown to directly regulate comCDE transcription. In this study, a transcriptional regulator, the catabolite control protein A (CcpA), was identified that directly regulated comCDE transcription. We confirmed that CcpA binds to the cis-acting catabolite response elements (cre) in the comCDE promoter region to regulate comCDE transcription and transformation. Moreover, CcpA can coregulate comCDE transcription with phosphorylated and dephosphorylated ComE. Regulation of comCDE transcription and transformation by CcpA was also affected by carbon source signals. Together, these insights demonstrate the versatility of CcpA and provide a theoretical basis for reducing the emergence of drug-resistant bacteria. IMPORTANCE Streptococcus pneumoniae is a major cause of bacterial infections in humans, such as pneumonia, bacteremia, meningitis, otitis media, and sinusitis. Like most streptococci, S. pneumoniae is naturally competent and employs this ability to augment its adaptive evolution. The current study illustrates CcpA, a carbon catabolite regulator, can participate in the competence process by regulating comCDE transcription, and this process is regulated by different carbon source signals. These hidden abilities are likely critical for adaptation and colonization in the environment.

Collective Quantum Magnetism in Nitrogen-Doped Nanographenes.

The emergence of quantum magnetism in nanographenes provides ample opportunities to fabricate purely organic devices for spintronics and quantum information. Although heteroatom doping is a viable way to engineer the electronic properties of nanographenes, the synthesis of doped nanographenes with collective quantum magnetism remains elusive. Here, a set of nitrogen-doped nanographenes (N-NGs) with atomic precision are fabricated on Au(111) through a combination of imidazole [2+2+2]-cyclotrimerization and cyclodehydrogenation reactions. High-resolution scanning probe microscopy measurements reveal the presence of collective quantum magnetism for nanographenes with three radicals, with spectroscopic features which cannot be captured by mean-field density functional theory calculations but can be well reproduced by Heisenberg spin model calculations. In addition, the mechanism of magnetic exchange interaction of N-NGs has been revealed and compared with their counterparts with pure hydrocarbons. Our findings demonstrate the bottom-up synthesis of atomically precise N-NGs which can be utilized to fabricate low-dimensional extended graphene nanostructures for realizing ordered quantum phases.

Glucose levels affect MgaSpn regulation on the virulence and adaptability of Streptococcus pneumoniae.

Streptococcus pneumoniae can regulate virulence gene expression by sensing environmental changes, which is key to its pathogenicity. The global transcription regulator MgaSpn of Streptococcus pneumoniae regulates virulence genes expression by directly binding to the promoter regions, but its role in response to different environments remains unclear. In this study, we found that glucose levels could affect phosphocholine content, which was mediated by MgaSpn. MgaSpn can also alter its anti-phagocytosis ability, depending on the availability of glucose. In addition, transcriptome analysis of wild-type D39s in low and high glucose concentrations revealed that MgaSpn was also involved in the regulation of carbon metabolism inhibition (carbon catabolite repression; CCR) and translation processes, which made S. pneumoniae highly competitive in fluctuating environments. In conclusion, MgaSpn is closely related to the virulence and environmental adaptability of Streptococcus pneumoniae.

Risk Factors for Carbapenem-resistant Pseudomonas aeruginosa Infection in Children.

BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is rapidly emerging as a life-threatening nosocomial infection. The study aimed to identify the risk factors for CRPA infection in children, especially antimicrobials use and invasive procedures. METHODS: A retrospective study was conducted in the Children's Hospital of Chongqing Medical University, which involved a cohort of patients with PA infection from January 2016 to December 2020. Patients were assigned to a carbapenem-susceptible PA group or to a CRPA group and matched using propensity-score matching. Univariate analysis and multivariate analysis were performed to estimate the risk factors of CRPA. RESULTS: One-thousand twenty-five patients were included in the study but 172 children were analyzed. Several factors were associated with CRPA infection according to univariate analysis ( P < 0.05), such as prior treatment with some antimicrobials and invasive procedures. However, only prior exposure to carbapenems (odds ratio [OR]: 0.102; confidence interval [CI]: 0.033-0.312; P < 0.001) and bronchoscopy (OR: 0.147; CI: 0.032-0.678; P = 0.014) during time at risk, previous invasive therapy in the last year (OR: 0.353; CI: 0.159-0.780; P = 0.013), and previous use of ß-lactams/ß-lactamase inhibitors within the last 90 days (OR: 0.327; CI: 0.121-0.884; P = 0.03) were considered independent risk factors by multivariate analysis. CONCLUSIONS: Those who had prior exposure to carbapenems and bronchoscopy were high-risk population to develop CRPA infection. The spread of CRPA could be influenced by invasive therapy, and we need pay attention to it. Moreover, we should take restrictions in the clinical use of carbapenems into account.

Study of the biological characteristics of human umbilical cord mesenchymal stem cells after long-time cryopreservation.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) have considerable potential in cell therapy. Cryopreservation represents the gold standard in cell storage, but its effect on hUC-MSCs is still not well understood. The aim of this study was to investigate the effect of one year of cryopreservation and thawing on the biological characteristics of hUC-MSCs from the same donors. Fresh hUC-MSCs were cryopreserved in commercial freezing medium (serum-free CellBanker 2) at passage 2. After one year of cryopreservation, the hUC-MSCs were thawed and subcultured to passage 4. The comparison was performed in terms of followings: cell count, viability, morphology, proliferation capacity, differentiation potential and chromosomal stability. The total cell count and viability of hUC-MSCs before and after one year of cryopreservation were 1 × 107 and 96.34% and 0.943 × 107 and 93.81%, respectively. Cryopreserved and fresh hUC-MSCs displayed a similar cell doubling times, expressed the markers CD73, CD90, CD105 and were negative for the markers CD34, CD45, and HLA-DR. Karyotypes were found to be normal after one year of cryopreservation. The trilineage differentiation properties were maintained after cryopreservation. However, when compared to freshly isolated hUC-MSCs from the same donor, cryopreserved hUC-MSCs exhibited decreased expression of osteogenesis- and chondrogenesis-related genes including Runx2, Sox9, and Col1a1, and increased expression of adipogenesis-related genes. These results demonstrated that cryopreservation did not affect cell morphology, surface marker expression, cell viability, proliferative capacity, or chromosomal stability. However, the osteogenic and chondrogenic differentiation capacities of cryopreserved hUC-MSCs were slightly reduced compared with those of fresh cells from the same donor.

MgaSpn is a negative regulator of capsule and phosphorylcholine biosynthesis and influences the virulence of Streptococcus pneumoniae D39.

Global transcriptional regulators are prevalent in gram-positive pathogens. The transcriptional regulators of the Mga/AtxA family regulate target gene expression by directly binding to the promoter regions, that results in the coordinated expression of virulence factors. The spd_1587 gene of Streptococcus pneumoniae strain D39 encodes MgaSpn, which shares sequence similarity with global transcriptional regulators of the Mga/AtxA family. In this study, we demonstrated that MgaSpn regulates the biosynthesis of the capsule and phosphorylcholine, which play key roles in disease severity in S. pneumoniae infections. MgaSpn directly binds to the cps and lic1 promoters and affects the biosynthesis of the capsule and phosphorylcholine. MgaSpn binds to two specific sites on the promoter of cps, one of which contains the -35 box of the promoter, with high affinity. Consistently, low-molecular-weight capsule components were observed in the mgaSpn-null mutant strain. Moreover, we found that phosphorylcholine content was notably increased in the unencapsulated mgaSpn mutant strain. The mgaSpn null mutant caused more severe systemic disease than the parental strain D39. These findings indicate that the pneumococcal MgaSpn protein can inhibit capsule and phosphorylcholine production, thereby affecting the virulence of S. pneumoniae.

Inactivation of Transcriptional Regulator FabT Influences Colony Phase Variation of Streptococcus pneumoniae.

Streptococcus pneumoniae is an opportunistic pathogen that can alter its cell surface phenotype in response to the host environment. We demonstrated that the transcriptional regulator FabT is an indirect regulator of capsular polysaccharide, an important virulence factor of Streptococcus pneumoniae. Transcriptome analysis between the wild-type D39s and D39ΔfabT mutant strains unexpectedly identified a differentially expressed gene encoding a site-specific recombinase, PsrA. PsrA catalyzes the inversion of 3 homologous hsdS genes in a type I restriction-modification (RM) system SpnD39III locus and is responsible for the reversible switch of phase variation. Our study demonstrated that upregulation of PsrA in a D39ΔfabT mutant correlated with an increased ratio of transparent (T) phase variants. Inactivation of the invertase PsrA led to uniform opaque (O) variants. Direct quantification of allelic variants of hsdS derivatives and inversions of inverted repeats indicated that the recombinase PsrA fully catalyzes the inversion mediated by IR1 and IR3, and FabT mediated the recombination of the hsdS alleles in PsrA-dependent and PsrA-independent manners. In addition, compared to D39s, the ΔfabT mutant exhibited reduced nasopharyngeal colonization and was more resistant to phagocytosis and less adhesive to epithelial cells. These results indicated that phase variation in the ΔfabT mutant also affects other cell surface components involved in host interactions. IMPORTANCE Streptococcus pneumoniae is a major human pathogen, and its virulence factors and especially the capsular polysaccharide have been extensively studied. In addition to virulence components that are present on its cell surface that directly interact with the host, S. pneumoniae undergoes a spontaneous and reversible phase variation that allows survival in different host environments. This phase variation is manipulated by the recombination of allelic hsdS genes that encode the sequence recognition proteins of the type I RM system SpnD39III locus. The recombination of hsdS alleles is catalyzed by the DNA invertase PsrA. Interestingly, we found the opaque colony morphology can be reversed by inactivation of the transcriptional regulator FabT, which regulates fatty acid biosynthesis. Inactivation of FabT leads to a significant decrease in capsule production and systematic virulence, but these phase variations do not correlate with the capsule production. This phase variation is mediated via the upregulated invertase PsrA in the ΔfabT mutant. These results identify an unexpected link between the specific phase variations and FabT that strongly suggests an underlying mechanism regulating the DNA invertase PsrA.

Designer spin order in diradical nanographenes.

The magnetic properties of carbon materials are at present the focus of intense research effort in physics, chemistry and materials science due to their potential applications in spintronics and quantum computing. Although the presence of spins in open-shell nanographenes has recently been confirmed, the ability to control magnetic coupling sign has remained elusive but highly desirable. Here, we demonstrate an effective approach of engineering magnetic ground states in atomically precise open-shell bipartite/nonbipartite nanographenes using combined scanning probe techniques and mean-field Hubbard model calculations. The magnetic coupling sign between two spins was controlled via breaking bipartite lattice symmetry of nanographenes. In addition, the exchange-interaction strength between two spins has been widely tuned by finely tailoring their spin density overlap, realizing a large exchange-interaction strength of 42 meV. Our demonstrated method provides ample opportunities for designer above-room-temperature magnetic phases and functionalities in graphene nanomaterials.

Engineering of Magnetic Coupling in Nanographene.

Nanographenes with sublattice imbalance host a net spin according to Lieb's theorem for bipartite lattices. Here, we report the on-surface synthesis of atomically precise nanographenes and their atomic-scale characterization on a gold substrate by using low-temperature noncontact atomic force microscopy and scanning tunneling spectroscopy. Our results clearly confirm individual nanographenes host a single spin of S=1/2 via the Kondo effect. In covalently linked nanographene dimers, two spins are antiferromagnetically coupled with each other as revealed by inelastic spin-flip excitation spectroscopy. The magnetic exchange interaction in dimers can be well engineered by tuning the local spin density distribution near the connection region, consistent with mean-field Hubbard model calculations. Our work clearly reveals the emergence of magnetism in nanographenes and provides an efficient way to further explore the carbon-based magnetism.

Advancing Image Understanding in Poor Visibility Environments: A Collective Benchmark Study.

Existing enhancement methods are empirically expected to help the high-level end computer vision task: however, that is observed to not always be the case in practice. We focus on object or face detection in poor visibility enhancements caused by bad weathers (haze, rain) and low light conditions. To provide a more thorough examination and fair comparison, we introduce three benchmark sets collected in real-world hazy, rainy, and low-light conditions, respectively, with annotated objects/faces. We launched the UG2+ challenge Track 2 competition in IEEE CVPR 2019, aiming to evoke a comprehensive discussion and exploration about whether and how low-level vision techniques can benefit the high-level automatic visual recognition in various scenarios. To our best knowledge, this is the first and currently largest effort of its kind. Baseline results by cascading existing enhancement and detection models are reported, indicating the highly challenging nature of our new data as well as the large room for further technical innovations. Thanks to a large participation from the research community, we are able to analyze representative team solutions, striving to better identify the strengths and limitations of existing mindsets as well as the future directions.

Intravitreal Injection of Human Retinal Progenitor Cells for Treatment of Retinal Degeneration.

BACKGROUND Retinal degeneration causes irreversible blindness. Human retinal progenitor cells (hRPCs) have the potential to treat retinal diseases. The vitreous cavity is a relatively immune-privileged site that is suitable for stem cell transplantation in the treatment of retinal diseases. This study aimed to evaluate the therapeutic efficacy and safety of intravitreal injection of hRPCs in retinal degeneration therapy. MATERIAL AND METHODS hRPCs were primary-cultured and injected into the vitreous cavity of RCS rats. To determine whether hRPCs formed teratomas in immune-deficient mice, hRPCs at different passages were transplanted into BALB/c-nu mice. The visual function was detected by electroretinography recording. Changes in the outer nuclear layer (ONL) were analyzed by histological testing and cell counting. The protective mechanism was further assessed by cytokine antibody array. RESULTS Intravitreal transplantation of hRPCs maintained retinal function and preserved retinal morphology. Importantly, grafted cells in the vitreous cavity were well tolerated, with no adverse effects. Teratoma was not formed in BALB/c-nu mice after hRPCs transplantation. The number of hRPCs-injected eyes and thickness of ONL in the hRPCs-treated group were higher than those in the untreated group and HBSS injection group. The cytokine antibody array revealed that hRPCs expressed GDF-15, PDGF-AA, EGF, and NT-4. CONCLUSIONS Our findings show that intravitreal injection of hRPCs is effective and safe in protecting photoreceptor cells in RCS rats, but were no longer effective at 12 weeks after transplantation. Moreover, hRPCs released multiple neurotrophic factors that may be involved in treating retinal disease.

Progranulin Mediates Proinflammatory Responses in Systemic Lupus Erythematosus: Implications for the Pathogenesis of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease caused by the disorders of immune regulation but its pathogenesis is poorly understood. Progranulin (PGRN) is an immunomodulatory protein that is upregulated in SLE patients. However, the factors involved in regulating the pathogenesis of SLE by PGRN are largely unknown. We sought to investigate the role and molecular mechanisms of PGRN in SLE to develop a novel therapeutic target. We used an animal model of SLE that was induced in PGRN-deficient and normal wild type (WT) mice using pristane. PGRN concentrations were measured in SLE and the impact of PGRN deficiency was examined by measuring tissue injury and immune responses of T cells (Th1, Th2, Th17, and Treg) and B cells. SLE patients and mice showed elevated PGRN levels. Compared with WT SLE mice, inflammatory cell infiltration, tissue edema, and necrosis were alleviated in PGRN-/- SLE mice and the levels of serum chemistry markers of tissue damage and the presence of anti-double-stranded DNA and anti-ribosomal protein P0 antibodies were all significantly decreased. We further discovered that PGRN deficiency could disturb the immune responses of T cell (Th1, Th2, Th17, and Treg) and B cell responses, leading to the decrease of inflammatory cytokines including interferon-γ and interleukin-17A and increased levels of regulatory B cells. PGRN plays a proinflammatory role in the development of SLE partially through promoting the production of autoantibodies and enhancing Th1 and Th17 cell responses. This may provide new therapeutic options for patients with SLE.

Elevated Levels of Platelet Activating Factor and Its Acetylhydrolase Indicate High Risk of Kawasaki Disease.

Kawasaki disease (KD) is a systemic vasculitis in children, which is related to inflammation and abnormal activation of immune system. Platelet activating factor (PAF) and its acetylhydrolase (PAF-AH) may play an important role in the pathogenesis of KD. This study aimed to investigate diagnosis and prognostic value of serum PAF and PAF-AH in KD. One hundred thirteen KD children were divided into coronary artery lesion (CAL) KD, noncoronary artery lesion (NCAL) KD, intravenous immunoglobulin (IVIG)-responsive KD, and IVIG-nonresponsive KD group. Seventy cases of fever control (F) group and 71 cases of normal control (N) group were set up. Peripheral venous blood was collected to detect serum PAF and PAF-AH levels, combined with other inflammatory mediators. Results showed that the serum levels of PAF and PAF-AH were significantly elevated in the KD group compared with F group and N group (P < 0.05). And the levels of conventional inflammatory mediators in KD group were significantly higher than those of F group (P < 0.05). In children with fever (KD group and F group), the area under the receiver operating characteristic curve (AUC) for PAF in prediction of KD was 0.804, and the estimated sensitivity and specificity were 79.6% and 74.3% with a cutoff of PAF >201.77 ng/mL, respectively; the AUC for PAF-AH in prediction of KD was 0.587, and the estimated sensitivity and specificity were 61.9% and 55.7% with a cutoff of PAF-AH >0.153 µmol/min/mL, respectively. Compared with NCAL group, PAF and C-reactive protein were higher in CAL group (P < 0.05). The AUC for PAF in prediction of CAL KD was 0.679, and the estimated sensitivity and specificity were 96.0% and 40.9% with a cutoff of PAF >225.52 ng/mL, respectively. Thus, serum levels of PAF and PAF-AH were significantly elevated in the acute phase of KD. Serum PAF and PAF-AH contributed to the diagnosis of KD, and serum PAF has a greater diagnostic value for KD. At the same time, elevated serum PAF has a certain predictive value for the occurrence of coronary artery lesions in Kawasaki disease rather than IVIG-nonresponsive KD.

Green chemical method for the synthesis of chromogenic fiber and its application for the detection and extraction of Hg2+ and Cu2+ in environmental medium.

To advocate environment friendly detection idea, we adopted the green chemical method to synthesis the 1-(2 amino ethyl) piperidine functionalized polyacrylonitrile fiber (APF) and the chromogenic fiber 4-(2-pyridylazo) resorcinol (APF-PAR). The APF has high adsorption selectivity of Hg2+ and Cu2+, and the change of structure, surface morphology and thermo-stability before and after adsorption have been characterized by the infrared spectra, scanning electron microscope and thermogravimetric analysis. The APF achieved the adsorption equilibrium of Hg2+ just in 25 min and the adsorption capacity is 435.1 mg/g, while the adsorption equilibrium of Cu2+ costs 30 min and the adsorption capacity is 141.7 mg/g. The chromogenic fiber APF-PAR can recognize the Hg2+ and Cu2+ in 2 s, which benefits from the rapid mass transfer and small fluid resistance of the chelating PAN fiber. The color changed from orange to purplish red due to the variation of HOMO-LOMO energy gaps during the reaction which confirmed by the UV-vis absorption spectrum. It also has high selectivity and excellent adsorption performance, which provides more convenient, accurate, reliable and faster testing methods of Hg2+ and Cu2+ in environmental medium.

Spin orbit torques induced magnetization reversal through asymmetric domain wall propagation in Ta/CoFeB/MgO structures.

The magnetization reversal induced by spin orbit torques in the presence of Dzyaloshinskii-Moriya interaction (DMI) in perpendicularly magnetized Ta/CoFeB/MgO structures were investigated by using a combination of Anomalous Hall effect measurement and Kerr effect microscopy techniques. By analyzing the in-plane field dependent spin torque efficiency measurements, an effective field value for the DMI of ~300 Oe was obtained, which plays a key role to stabilize Néel walls in the film stack. Kerr imaging reveals that the current-induced reversal under small and medium in-plane field was mediated by domain nucleation at the edge of the Hall bar, followed by asymmetric domain wall (DW) propagation. However, as the in-plane field strength increases, an isotropic DW expansion was observed before reaching complete reversal. Micromagnetic simulations of the DW structure in the CoFeB layer suggest that the DW configuration under the combined effect of the DMI and the external field is responsible for the various DW propagation behaviors.

ComE, an Essential Response Regulator, Negatively Regulates the Expression of the Capsular Polysaccharide Locus and Attenuates the Bacterial Virulence in Streptococcus pneumoniae.

The capsular polysaccharide (CPS) of Streptococcus pneumoniae is the main virulence factors required for effective colonization and invasive disease. The capacity to regulate CPS production at the transcriptional level is critical for the survival of S. pneumoniae in different host niches, but little is known about the transcription regulators of cps locus. In the present study, we isolated and identified the response regulator ComE, the master competence switch in transformation of S. pneumoniae, as a transcriptional regulator of cps locus by DNA affinity chromatography-pulldown, MALDI-TOF mass spectrometry (MS) and electrophoretic mobility shift assay (EMSA). Our results showed that phosphorylated mimetic of ComE (ComED58E) bound specifically to the cps locus prompter in vitro, and phosphorylated ComE negatively impacted both cps locus transcription and CPS production attenuating the pneumococcal virulence in vivo. Compared with D39-WT strain, D39ΔcomE mutant exhibited much thicker capsule, attenuated nasopharyngeal colonization and enhanced virulence in both pneumonia and bacteremia models of Balb/c mice. Furthermore, it was demonstrated that CSP-ComD/E competence system involved in regulating negatively the CPS production during the progress of transformation in D39. Our CSP1 induction experiment results showed that the expression of ComE in D39-WT strain increased powerfully by 120% after 10 min of CSP1 induction, but the CPS production in D39-WT strain decreased sharply by 67.1% after 15 min of CSP1 induction. However, the CPS production in D39ΔcomE mutant was almost constant during the whole stage of induction. Additionally, we found that extracellular glucose concentration could affect both the expression of ComE and CPS production of D39 in vitro. Taken together, for the first time, we report that ComE, as a transcriptional regulator of cps locus, plays an important role in transcriptional regulation of cps locus and capsular production level.

CpsR, a GntR family regulator, transcriptionally regulates capsular polysaccharide biosynthesis and governs bacterial virulence in Streptococcus pneumoniae.

Transcriptional regulation of capsule expression is critical for pneumococcal transition from carriage to infection, yet the underlying mechanism remains incompletely understood. Here, we describe the regulation of capsular polysaccharide, one of the most important pneumococcal virulence factor by a GntR family regulator, CpsR. Electrophoretic mobility-shift assays have shown the direct interaction between CpsR and the cps promoter (cpsp), and their interaction could be competitively interfered by glucose. DNase I footprinting assays localized the binding site to a region -146 to -114 base pairs relative to the transcriptional start site of the cps locus in S. pneumoniae D39. We found that CpsR negatively controlled the transcription of the cps locus and hence CPS production, which was confirmed by fine-tuning expression of CpsR in a ΔcpsR complemented strain. Increased expression of CpsR in complemented strain led to a decreased resistance to the whole-blood-mediated killing, suggesting a protective role for CpsR-cpsp interaction in the establishment of invasive infection. Finally, animal experiments showed that CpsR-cpsp interaction was necessary for both pneumococcal colonization and invasive infection. Taken together, our results provide a thorough insight into the regulation of capsule production mediated by CpsR and its important roles in pneumococcal pathogenesis.