-
Frontiers in Immunology 2024Protein kinases are indispensable reversible molecular switches that adapt and control protein functions during cellular processes requiring rapid responses to internal...
INTRODUCTION
Protein kinases are indispensable reversible molecular switches that adapt and control protein functions during cellular processes requiring rapid responses to internal and external events. Bacterial infections can affect kinase-mediated phosphorylation events, with consequences for both innate and adaptive immunity, through regulation of antigen presentation, pathogen recognition, cell invasiveness and phagocytosis. (), a human respiratory tract pathogen and a major cause of community-acquired pneumoniae, affects phosphorylation-based signalling of several kinases, but the pneumococcal mediator(s) involved in this process remain elusive. In this study, we investigated the influence of pneumococcal HO on the protein kinase activity of the human lung epithelial H441 cell line, a generally accepted model of alveolar epithelial cells.
METHODS
We performed kinome analysis using PamGene microarray chips and protein analysis in Western blotting in H441 lung cells infected with wild type () or with -a deletion mutant strongly attenuated in HO production- to assess the impact of pneumococcal hydrogen peroxide (HO) on global protein kinase activity profiles.
RESULTS
Our kinome analysis provides direct evidence that kinase activity profiles in infected H441 cells significantly vary according to the levels of pneumococcal HO. A large number of kinases in H441 cells infected with are significantly downregulated, whereas this no longer occurs in cells infected with the mutant strain, which lacks HO In particular, we describe for the first time HO-mediated downregulation of Protein kinase B (Akt1) and activation of lymphocyte-specific tyrosine protein kinase (Lck) via HO-mediated phosphorylation.
Topics: Streptococcus pneumoniae; Hydrogen Peroxide; Humans; Phosphorylation; Host-Pathogen Interactions; Cell Line; Protein Kinases; Pneumococcal Infections; Signal Transduction
PubMed: 38903521
DOI: 10.3389/fimmu.2024.1414195 -
Cureus May 2024Meningitis, an infection of the meninges of the central nervous system (CNS), can advance quickly and carries a mortality rate reaching 30% among affected patients. It...
Meningitis, an infection of the meninges of the central nervous system (CNS), can advance quickly and carries a mortality rate reaching 30% among affected patients. It may become complicated by conditions such as hydrocephalus, ventriculitis, and cerebral abscess. Here, we describe a case of meningitis that was complicated by pyogenic ventriculitis and hydrocephalus in a patient with diffuse large B-cell lymphoma (DLBCL) who underwent chemotherapy and radiotherapy. The patient presented with acute change in mental status and high-grade fever, with few episodes of non-bloody vomiting. Blood culture and cerebrospinal fluid (CSF) culture grew which was sensitive to ceftriaxone. CT scan of the head showed ventriculomegaly, pansinusitis, and a large left mastoid effusion. MRI of the brain showed layering in ventricles, hydrocephalus, and dural enhancement consistent with pachymeningitis. She was treated with ceftriaxone for 21 days with a meaningful outcome. She was discharged home with near-baseline mental capacity for further physical therapy.
PubMed: 38903366
DOI: 10.7759/cureus.60800 -
BMC Infectious Diseases Jun 2024Pneumococcal pneumonia (PP) is a serious infection caused by Streptococcus pneumoniae (pneumococcus), with a wide spectrum of clinical manifestations. The aim of this...
BACKGROUND
Pneumococcal pneumonia (PP) is a serious infection caused by Streptococcus pneumoniae (pneumococcus), with a wide spectrum of clinical manifestations. The aim of this study was to analyze the comorbidity factors that influenced the mortality in patients with asplenia according to PP.
METHODS
Discharge reports from the Spanish Minimum Basic Data Set (MBDS) was used to retrospectively analyze patients with asplenia and PP, from 1997 to 2021. Elixhauser Comorbidity Index (ECI) was calculated to predict in-hospital mortality (IHM).
RESULTS
97,922 patients with asplenia were included and 381 cases of PP were identified. The average age for men was 63.87 years and for women 65.99 years. In all years, ECI was larger for splenectomized than for non-splenectomized patients, with men having a higher mean ECI than women. An association was found between risk factors ECI, splenectomy, age group, sex, pneumococcal pneumonia, and increased mortality (OR = 0.98; 95% CI: 0.97-0.99; p < 0.001). The IHM increased steadily with the number of comorbidities and index scores in 1997-2021.
CONCLUSIONS
Asplenia remain a relevant cause of hospitalization in Spain. Comorbidities reflected a great impact in patients with asplenia and PP, which would mean higher risk of mortality.
Topics: Humans; Male; Female; Middle Aged; Pneumonia, Pneumococcal; Spain; Aged; Retrospective Studies; Comorbidity; Hospital Mortality; Risk Factors; Splenectomy; Streptococcus pneumoniae; Adult; Aged, 80 and over; Inpatients; Hospitalization
PubMed: 38902621
DOI: 10.1186/s12879-024-09517-4 -
Journal of Innate Immunity Jun 2024The hydrophilic, polymeric chain of the lipoteichoic acid (LTA) of the Gram-positive pathobiont Streptococcus pneumoniae is covalently linked to the glycosylglycerolipid...
INTRODUCTION
The hydrophilic, polymeric chain of the lipoteichoic acid (LTA) of the Gram-positive pathobiont Streptococcus pneumoniae is covalently linked to the glycosylglycerolipid -D-glucopyranosyl-(1,3)-diacylglycerol by the lipoteichoic acid ligase TacL, leading to its fixation in the cytoplasmic membrane. Pneumococcal LTA, sharing identical repeating units with the wall teichoic acids, are dispensable for normal growth but required for full-virulence in invasive infections.
METHODS
Mutants deficient in TacL and complemented strains constructed were tested for their growth, resistance against oxidative stress and susceptibility against antimicrobial peptides. Further, the membrane fluidity of pneumococci, their capability to adhere to lung epithelial cells and virulence in a Galleria mellonella as well as intranasal mouse infection model were assessed.
RESULTS
In the present study, we indicate that LTA is already indispensable for pneumococcal adherence to human nasopharyngeal cells and colonization in an intranasal mouse infection model. Mutants deficient for TacL did not show morphological defects. However, our analysis of pneumococcal membranes in different serotypes showed an altered membrane fluidity and surface protein abundance of lipoproteins in mutants deficient for LTA but not WTA. These mutants had a decreased membrane fluidity, exhibited higher amounts of lipoproteins, and showed an increased susceptibility to antimicrobial peptides. In complemented mutant strains this defect was fully restored.
CONCLUSION
Taken together, LTA is crucial for colonization and required to effectively protect pneumococci from innate immune defence mechanisms by maintaining the membrane integrity.
PubMed: 38901409
DOI: 10.1159/000539934 -
BMC Infectious Diseases Jun 2024Invasive pneumococcal disease (IPD) is a significant health concern in children worldwide. In this study, we aimed to analyze the clinical features, antibiotic...
BACKGROUND
Invasive pneumococcal disease (IPD) is a significant health concern in children worldwide. In this study, we aimed to analyze the clinical features, antibiotic resistance, and risk variables for poor outcomes in patients with IPD in Hangzhou.
METHODS
A retrospective single-centre study was performed using the pediatric intensive care (PIC) database from 2010 to 2018. The clinical characteristics, laboratory data, antimicrobial resistance, and risk factors for in-hospital mortality and sepsis in patients with IPD in intensive care units (ICUs) were analyzed systematically.
RESULTS
A total of 178 IPD patients were included in the study. The majority of the IPD children were 2-10 years old. Antimicrobial resistance tests of S. pneumoniae isolates revealed high resistance to erythromycin, tetracycline and compound sulfamethoxazole (SMZ-Co). All the isolates were sensitive to vancomycin, linezolid, moxifloxacin, telithromycin, ofloxacin, and levofloxacin. IPD patients may experience poor outcomes, including death and sepsis. The in-hospital mortality was 3.93%, and 34.27% of patients suffered from sepsis. Temperature (OR 3.80, 95% CI 1.62-8.87; P = 0.0021), Partial Pressure of Oxygen in Arterial Blood (PaO) (OR 0.99, 95% CI 0.98-1.00; P = 0.0266), and albumin (OR 0.89, 95% CI 0.80-0.99; P = 0.0329) were found to be independent risk factors for sepsis in children with IPD.
CONCLUSION
Pediatric IPD deserves attention in China. Appropriate surveillance and antibiotic selection are crucial in managing resistant strains. Early identification of high-risk individuals with risk factors contributes to the development of appropriate treatment strategies.
Topics: Humans; China; Pneumococcal Infections; Child; Male; Risk Factors; Retrospective Studies; Female; Child, Preschool; Streptococcus pneumoniae; Anti-Bacterial Agents; Infant; Hospital Mortality; Microbial Sensitivity Tests; Sepsis; Adolescent; Intensive Care Units, Pediatric; Drug Resistance, Bacterial
PubMed: 38898407
DOI: 10.1186/s12879-024-09493-9 -
Microbial Genomics Jun 2024Since the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in Malawi in 2011, there has been persistent carriage of vaccine serotype (VT) , despite...
Expansion of pneumococcal serotype 23F and 14 lineages with genotypic changes in capsule polysaccharide locus and virulence gene profiles post introduction of pneumococcal conjugate vaccine in Blantyre, Malawi.
Since the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in Malawi in 2011, there has been persistent carriage of vaccine serotype (VT) , despite high vaccine coverage. To determine if there has been a genetic change within the VT capsule polysaccharide (cps) loci since the vaccine's introduction, we compared 1022 whole-genome-sequenced VT isolates from 1998 to 2019. We identified the clonal expansion of a multidrug-resistant, penicillin non-susceptible serotype 23F GPSC14-ST2059 lineage, a serotype 14 GPSC9-ST782 lineage and a novel serotype 14 sequence type GPSC9-ST18728 lineage. Serotype 23F GPSC14-ST2059 had an I253T mutation within the capsule oligosaccharide repeat unit polymerase Wzy protein, which is predicted to alter the protein pocket cavity. Moreover, serotype 23F GPSC14-ST2059 had SNPs in the DNA binding sites for the cps transcriptional repressors CspR and SpxR. Serotype 14 GPSC9-ST782 harbours a non-truncated version of the large repetitive protein (Lrp), containing a Cna protein B-type domain which is also present in proteins associated with infection and colonisation. These emergent lineages also harboured genes associated with antibiotic resistance, and the promotion of colonisation and infection which were absent in other lineages of the same serotype. Together these data suggest that in addition to serotype replacement, modifications of the capsule locus associated with changes in virulence factor expression and antibiotic resistance may promote vaccine escape. In summary, the study highlights that the persistence of vaccine serotype carriage despite high vaccine coverage in Malawi may be partly caused by expansion of VT lineages post-PCV13 rollout.
Topics: Streptococcus pneumoniae; Pneumococcal Vaccines; Humans; Serogroup; Malawi; Bacterial Capsules; Pneumococcal Infections; Vaccines, Conjugate; Polysaccharides, Bacterial; Virulence; Genotype; Whole Genome Sequencing; Bacterial Proteins; Virulence Factors; Child, Preschool; Polymorphism, Single Nucleotide; Infant; Male
PubMed: 38896467
DOI: 10.1099/mgen.0.001264 -
Pneumococcal and Influenza Vaccination Coverage in Patients with Heart Failure: A Systematic Review.Journal of Clinical Medicine May 2024As heart failure (HF) patients face increased vulnerability to respiratory infections, optimizing pneumococcal and influenza vaccination coverage becomes pivotal for... (Review)
Review
As heart failure (HF) patients face increased vulnerability to respiratory infections, optimizing pneumococcal and influenza vaccination coverage becomes pivotal for mitigating additional health risks and reducing hospitalizations, morbidity, and mortality rates within this population. In this specific subpopulation of patients, vaccination coverage for pneumococcal and influenza holds heightened significance compared to other vaccines due to their susceptibility to respiratory infections, which can exacerbate existing cardiovascular conditions and lead to severe complications or even death. However, despite the recognized benefits, vaccination coverage among HF patients remains below expectations. The aim of the present systematic review was to assess the vaccination coverage for influenza and pneumococcus in HF patients from 2005 to 2023 and the vaccination's effects on survival and hospitalizations. The authors developed the protocol of the review in accordance with the PRISMA guidelines, and the search was performed in databases including PubMed and Scopus. After the initial search, 851 studies were found in PubMed Library and 1961 in Scopus (total of 2812 studies). After the initial evaluation, 23 publications were finally included in the analysis. The total study population consisted of 6,093,497 participants. Regarding the influenza vaccine, vaccination coverage ranged from low rates of 2.5% to very high rates of 97%, while the respective pneumococcal vaccination coverage ranged from 20% to 84.6%. Most studies demonstrated a beneficial effect of vaccination on survival and hospitalizations. The present systematic review study showed a wide variety of vaccination coverage among patients with heart failure.
PubMed: 38892740
DOI: 10.3390/jcm13113029 -
Nature Communications Jun 2024Efficient utilization of nutrients is crucial for microbial survival and virulence. The same nutrient may be utilized by multiple catabolic pathways, indicating that the...
Efficient utilization of nutrients is crucial for microbial survival and virulence. The same nutrient may be utilized by multiple catabolic pathways, indicating that the physical and chemical environments for induction as well as their functional roles may differ. Here, we study the tagatose and Leloir pathways for galactose catabolism of the human pathogen Streptococcus pneumoniae. We show that galactose utilization potentiates pneumococcal virulence, the induction of galactose catabolic pathways is influenced differentially by the concentration of galactose and temperature, and sialic acid downregulates galactose catabolism. Furthermore, the genetic regulation and in vivo induction of each pathway differ, and both galactose catabolic pathways can be turned off with a galactose analogue in a substrate-specific manner, indicating that galactose catabolic pathways can be potential drug targets.
Topics: Streptococcus pneumoniae; Galactose; Gene Expression Regulation, Bacterial; Virulence; Animals; Hexoses; Mice; Metabolic Networks and Pathways; Humans; Pneumococcal Infections; N-Acetylneuraminic Acid; Temperature; Bacterial Proteins; Female
PubMed: 38886409
DOI: 10.1038/s41467-024-49619-w -
Archivos de Bronconeumologia May 2024Chronic respiratory diseases (CRD) are responsible for more than four million deaths worldwide and have become especially prevalent in developed countries. Although the... (Review)
Review
Chronic respiratory diseases (CRD) are responsible for more than four million deaths worldwide and have become especially prevalent in developed countries. Although the current therapies help manage daily symptoms and improve patients' quality of life, there is a major need to prevent exacerbations triggered mainly by respiratory infections. Therefore, CRD patients are a prime target for vaccination against infectious agents. In the present manuscript we review the state of the art of available vaccines specifically indicated in patients with CRDs. In addition to pneumococcus, influenza, pertussis, and SARS-CoV-2 vaccines, recently added immunization options like vaccines and monoclonal antibodies against respiratory syncytial virus, are particularly interesting in CRD patients. As new products reach the market, health authorities must be agile in updating immunization recommendations and in the programming of the vaccination of vulnerable populations such as patients with CRDs. Organizational and educational strategies might prove useful to increase vaccine uptake by CRD patients.
PubMed: 38876918
DOI: 10.1016/j.arbres.2024.05.026 -
Infectious Diseases Now Jun 2024In 2023 in France, 15 valent- pneumococcal conjugate vaccines (PCV15) have been recommended as alternatives to PCV13 for children < 2 years. PCV20 has been...
INTRODUCTION
In 2023 in France, 15 valent- pneumococcal conjugate vaccines (PCV15) have been recommended as alternatives to PCV13 for children < 2 years. PCV20 has been recommended for at-risk adults but not yet for infants, while PCV21 targets older adults. We endeavored to estimate the potential benefit of new pneumococcal vaccines in preventing invasive pneumococcal infections by comparing serotype extension to PCV13.
PATIENTS AND METHODS
The National Reference Centre for Pneumococci distributed S. pneumoniae IPD serotypes from children and adults.
RESULTS
In 2022, for children under 24 months, PCV15 and PCV20 ensured 10 % and 36 % more coverage against IPD than PCV13. For adults, PCV15, PCV20, and PCV21 covered up to 3 %, 26 %, and 50 % more IPD cases than PCV13.
CONCLUSION
The new generation of pneumococcal vaccines could reduce the burden of invasive pneumococcal infections through serotype extension. Additional studies are needed in parallel to optimize their utilization and improve vaccine coverage in France.
PubMed: 38876363
DOI: 10.1016/j.idnow.2024.104937