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Infection and Immunity Jun 2024The major gram-positive pathogen group A (GAS) is a model organism for studying microbial epidemics as it causes waves of infections. Since 1980, several GAS epidemics...
The major gram-positive pathogen group A (GAS) is a model organism for studying microbial epidemics as it causes waves of infections. Since 1980, several GAS epidemics have been ascribed to the emergence of clones producing increased amounts of key virulence factors such as streptolysin O (SLO). Herein, we sought to identify mechanisms underlying our recently identified temporal clonal emergence among GAS, given that emergent strains did not produce augmented levels of virulence factors relative to historic isolates. By creating and analyzing isoallelic strains, we determined that a conserved mutation in a previously undescribed gene encoding a putative carbonic anhydrase was responsible for the defective growth observed in the emergent strains. We also identified that the emergent strains survived better inside macrophages and killed macrophages at lower rates than the historic strains. the creation of isogenic mutant strains, we linked the emergent strain "survival" phenotype to the downregulation of the SLO encoding gene and upregulation of the operon which encodes proteins involved in defense against extracellular oxidative stress. Our findings are in accord with recent surveillance studies which found a high ratio of mucosal (i.e., pharyngeal) relative to invasive infections among GAS. Since ever-increasing virulence is unlikely to be evolutionarily advantageous for a microbial pathogen, our data further understanding of the well-described oscillating patterns of virulent GAS infections by demonstrating mechanisms by which emergent strains adapt a "survival" strategy to outcompete previously circulating isolates.
PubMed: 38888310
DOI: 10.1128/iai.00152-24 -
PloS One 2024This study aims to explore the applicability of narrow-band imaging (NBI) involving the Ni classification for the diagnosis of nasopharyngeal mucosal lesions in order to...
BACKGROUND
This study aims to explore the applicability of narrow-band imaging (NBI) involving the Ni classification for the diagnosis of nasopharyngeal mucosal lesions in order to distinguish malignant tumours (NPT) from non-malignant lesions.
METHODS
Each patient (n = 53) with a suspected nasopharyngeal lesion underwent a trans-nasal flexible video endoscopy with an optical filter for NBI. We assessed the suspected area using white light imaging (WLI) in terms of location and morphology as well as the vascular pattern (using Ni classification of nasopharyngeal microvessels) and surrounding tissue by using NBI. Based on the results of the NBI and WLI, patients were classified into "positive" or "negative" groups. All lesions of the nasopharynx were biopsied and submitted for final histological evaluation.
RESULTS
NBI showed higher sensitivity, specificity, and accuracy than WLI. There was a significant correlation between the final histological result and the NBI pattern of the NPT: Chi2(1) = 31.34; p = 0.000001 and the WLI assessment of the NPT: Chi2(1) = 14.78; p = 0.00012.
CONCLUSIONS
The assessment of the NPT in NBI using Ni NBI classification proved valuable in suspected mucosa assessment. NBI not only confirms the suspicious areas in WLI, but it also shows microlesions beyond the scope of WLI and allows for proper sampling.
Topics: Humans; Narrow Band Imaging; Female; Nasopharyngeal Neoplasms; Male; Middle Aged; Nasopharynx; Adult; Aged; Sensitivity and Specificity; Young Adult; Adolescent; Aged, 80 and over; Endoscopy
PubMed: 38885230
DOI: 10.1371/journal.pone.0302043 -
Indian Journal of Otolaryngology and... Jun 2024A case of mpox pharyngitis in absence of cutaneous lesions is reported. Usually, clinical presentation is either a cutaneous eruption or a combination of cutaneous and...
A case of mpox pharyngitis in absence of cutaneous lesions is reported. Usually, clinical presentation is either a cutaneous eruption or a combination of cutaneous and mucosal lesions. In patients with atypical pharyngitis, regardless of the presence of skin lesions, pharyngeal swabs should be collected to rule out mpox.
PubMed: 38883515
DOI: 10.1007/s12070-024-04567-1 -
European Journal of Surgical Oncology :... Jun 2024The aim of this multicenter study was to evaluate the effectiveness and safety of electrochemotherapy (ECT) for the treatment of mucosal tumors in the head and neck. A...
The aim of this multicenter study was to evaluate the effectiveness and safety of electrochemotherapy (ECT) for the treatment of mucosal tumors in the head and neck. A total of 71 patients with 84 nodules of different histologies in the oral cavity, pharynx and larynx treated by ECT were evaluated. The data were collected from the InspECT database from 10 participating centers throughout Europe. Primary and recurrent/secondary tumors of different histologies were treated. The overall response rate was 65 %, with a 33 % complete response rate with limited side effects. The response rates of the primary and secondary tumors were not different. However, smaller tumors responded better than tumors larger than 3 cm in diameter. Furthermore, the tumors that were treated with curative intent responded significantly better than those treated with palliative intent. This study demonstrated the feasibility, safety and effectiveness of ECT in a larger cohort of patients with mucosal lesions in the head and neck region. Based on the available data, ECT can be used for the treatment of recurrent and, in some cases, primary mucosal tumors located in the oral cavity, larynx, and pharynx. A better response was obtained in patients with smaller primary tumors treated with curative intent.
PubMed: 38870873
DOI: 10.1016/j.ejso.2024.108473 -
Laryngoscope Investigative... Jun 2024This scoping review seeks to understand the existing research in otolaryngological mucosal emphysematous infections and to elucidate gaps in knowledge in the field. We...
OBJECTIVE
This scoping review seeks to understand the existing research in otolaryngological mucosal emphysematous infections and to elucidate gaps in knowledge in the field. We also present a case of bilateral necrotizing tonsillitis in an immunocompromised patient with the first reported imaging findings of emphysematous abscess of the tonsils.
DATA SOURCES
PubMed, Embase, Web of Science.
REVIEW METHODS
We conducted our review according to the Preferred Reporting Items for Systematic Reviews extension for Scoping Reviews. Patient presentation, management, and outcomes were summarized. We also describe the case of a patient with aplastic anemia found to have emphysematous tonsillitis, managed with intubation, broad spectrum intravenous antibiotics and bilateral tonsillectomy.
RESULTS
We identified seven case reports or series, involving nine total patients, who presented with emphysematous epiglottitis, supraglottitis, or tonsillitis. The hallmark imaging characteristic was submucosal "gas bubble" on computed tomography. Presenting symptoms included dysphagia, odynophagia, dysphonia, cough, and fever. Both immunocompetent and immunocompromised patients were affected. All patients were treated with broad spectrum antibiotics, and most with steroids. Patients at risk of airway compromise also underwent intubation and surgical drainage or debridement of the emphysematous infection.
CONCLUSION
Emphysematous pharyngeal infections are rare but potentially life-threatening infections that can progress rapidly, resulting in airway compromise and sepsis in both immunocompetent and immunocompromised individuals. We highlight the importance of swift intervention, with intubation and surgical intervention often required for severe cases. More research is needed on common pathogens and patient risk factors to guide future medical and surgical management.
PubMed: 38803461
DOI: 10.1002/lio2.1274 -
Scientific Reports May 2024Mucosal immunity plays a major role not only in the prevention but probably also in the outcomes of COVID-19. An enhanced production of secretory immunoglobulin A (sIgA)...
Mucosal immunity plays a major role not only in the prevention but probably also in the outcomes of COVID-19. An enhanced production of secretory immunoglobulin A (sIgA) might contribute to the activation of the immune response mechanisms. To assess the levels of sIgA produced by epithelial cells in the nasal and pharyngeal mucosa and those measured in salivary gland secretions and to study the course of COVID-19 following the combined scheme of intranasal and subcutaneous administration of a bacteria-based immunostimulant agent. This study included 69 patients, aged between 18 and 60, who had moderate COVID-19 infection. They were divided into two groups: Group 1 (control group) included 39 patients who received only background therapy, and Group 2 was made up of 30 patients who received background therapy in combination with the Immunovac VP4 vaccine, a bacteria-based immunostimulant agent, which was given for 11 days starting from the day of admission to hospital. The levels of sIgA were measured by ELISA in epithelial, nasal and pharyngeal swabs, and salivary gland secretions at baseline and on days 14 and 30. The combined scheme of intranasal and subcutaneous administration of the Immunovac VP4 vaccine in the complex therapy of patients with COVID-19 is accompanied by increased synthesis of sIgA in nasal and pharyngeal swabs, more intense decrease in the level of C-reactive protein (CRP) and reduction in the duration of fever and length of hospitalization compared to the control group. Prescribing a immunostimulant agent containing bacterial ligands in complex therapy for COVID-19 patients helps to enhance mucosal immunity and improves the course of the disease.
Topics: Humans; Immunoglobulin A, Secretory; COVID-19; Female; Adult; Male; Middle Aged; SARS-CoV-2; Adjuvants, Immunologic; COVID-19 Vaccines; Immunity, Mucosal; Young Adult; Adolescent; Administration, Intranasal
PubMed: 38750098
DOI: 10.1038/s41598-024-61341-7 -
PLoS Pathogens May 2024Infants are highly susceptible to invasive respiratory and gastrointestinal infections. To elucidate the age-dependent mechanism(s) that drive bacterial spread from the...
Infants are highly susceptible to invasive respiratory and gastrointestinal infections. To elucidate the age-dependent mechanism(s) that drive bacterial spread from the mucosa, we developed an infant mouse model using the prevalent pediatric respiratory pathogen, Streptococcus pneumoniae (Spn). Despite similar upper respiratory tract (URT) colonization levels, the survival rate of Spn-infected infant mice was significantly decreased compared to adults and corresponded with Spn dissemination to the bloodstream. An increased rate of pneumococcal bacteremia in early life beyond the newborn period was attributed to increased bacterial translocation across the URT barrier. Bacterial dissemination in infant mice was independent of URT monocyte or neutrophil infiltration, phagocyte-derived ROS or RNS, inflammation mediated by toll-like receptor 2 or interleukin 1 receptor signaling, or the pore-forming toxin pneumolysin. Using molecular barcoding of Spn, we found that only a minority of bacterial clones in the nasopharynx disseminated to the blood in infant mice, indicating the absence of robust URT barrier breakdown. Rather, transcriptional profiling of the URT epithelium revealed a failure of infant mice to upregulate genes involved in the tight junction pathway. Expression of many such genes was also decreased in early life in humans. Infant mice also showed increased URT barrier permeability and delayed mucociliary clearance during the first two weeks of life, which corresponded with tighter attachment of bacteria to the respiratory epithelium. Together, these results demonstrate a window of vulnerability during postnatal development when altered mucosal barrier function facilitates bacterial dissemination.
Topics: Animals; Pneumococcal Infections; Mice; Streptococcus pneumoniae; Humans; Animals, Newborn; Disease Models, Animal; Mice, Inbred C57BL; Respiratory Mucosa; Female; Nasopharynx
PubMed: 38718049
DOI: 10.1371/journal.ppat.1012111 -
Microbiology Spectrum Jun 2024Recent case reports and epidemiological data suggest that fungal infections represent an underappreciated complication among people with severe COVID-19. However, the...
UNLABELLED
Recent case reports and epidemiological data suggest that fungal infections represent an underappreciated complication among people with severe COVID-19. However, the frequency of fungal colonization in patients with COVID-19 and associations with specific immune responses in the airways remain incompletely defined. We previously generated a single-cell RNA-sequencing data set characterizing the upper respiratory microenvironment during COVID-19 and mapped the relationship between disease severity and the local behavior of nasal epithelial cells and infiltrating immune cells. Our previous study, in agreement with findings from related human cohorts, demonstrated that a profound deficiency in host immunity, particularly in type I and type III interferon signaling in the upper respiratory tract, is associated with rapid progression to severe disease and worse clinical outcomes. We have now performed further analysis of this cohort and identified a subset of participants with severe COVID-19 and concurrent detection of species-derived transcripts within samples collected from the nasopharynx and trachea. Here, we present the clinical characteristics of these individuals. Using matched single-cell transcriptomic profiles of these individuals' respiratory mucosa, we identify epithelial immune signatures suggestive of IL17 stimulation and anti-fungal immunity. Further, we observe a significant expression of anti-fungal inflammatory cascades in the nasal and tracheal epithelium of all participants who went on to develop severe COVID-19, even among participants without detectable genetic material from fungal pathogens. Together, our data suggest that IL17 stimulation-in part driven by colonization-and blunted interferon signaling represent a common feature of severe COVID-19 infection.
IMPORTANCE
In this paper, we present an analysis suggesting that symptomatic and asymptomatic fungal coinfections can impact patient disease progression during COVID-19 hospitalization. By looking into the presence of other pathogens and their effect on the host immune response during COVID-19 hospitalizations, we aim to offer insight into an underestimated scenario, furthering our current knowledge of determinants of severity that could be considered for future diagnostic and intervention strategies.
Topics: Humans; Interleukin-17; COVID-19; Coinfection; Interferon Type I; Male; SARS-CoV-2; Middle Aged; Female; Epithelial Cells; Adult; Nasal Mucosa; Aged; Nasopharynx; Candidiasis; Mycoses
PubMed: 38687064
DOI: 10.1128/spectrum.03516-23 -
BioRxiv : the Preprint Server For... Apr 2024The major gram-positive pathogen group A (GAS) is a model organism for studying microbial epidemics as it causes waves of infections. Since 1980, several GAS epidemics...
The major gram-positive pathogen group A (GAS) is a model organism for studying microbial epidemics as it causes waves of infections. Since 1980, several GAS epidemics have been ascribed to the emergence of clones producing increased amounts of key virulence factors such as streptolysin O (SLO). Herein, we sought to identify mechanisms underlying our recently identified temporal clonal emergence amongst GAS, given that emergent strains did not produce augmented levels of virulence factors relative to historic isolates. Through the creation and analysis of isoallelic strains, we determined that a conserved mutation in a previously undescribed gene encoding a putative carbonic anhydrase was responsible for the defective growth observed in the emergent strains. We also identified that the emergent strains survived better inside macrophages and killed macrophages at lower rates relative to the historic strains. Via creation of isogenic mutant strains, we linked the emergent strain "survival" phenotype to the downregulation of the SLO encoding gene and upregulation of the operon which encodes proteins involved in defense against extracellular oxidative stress. Our findings are in accord with recent surveillance studies which found high ratio of mucosal (i.e., pharyngeal) relative to invasive infections amongst GAS. Inasmuch as ever-increasing virulence is unlikely to be evolutionary advantageous for a microbial pathogen, our data furthers understanding of the well described oscillating patterns of virulent GAS infections by demonstrating mechanisms by which emergent strains adapt a "survival" strategy to outcompete previously circulating isolates.
PubMed: 38645060
DOI: 10.1101/2024.04.09.588776 -
Infection and Immunity May 2024, a common colonizer of the upper respiratory tract, invades nasopharyngeal epithelial cells without causing disease in healthy participants of controlled human...
, a common colonizer of the upper respiratory tract, invades nasopharyngeal epithelial cells without causing disease in healthy participants of controlled human infection studies. We hypothesized that surface expression of pneumococcal lipoproteins, recognized by the innate immune receptor TLR2, mediates epithelial microinvasion. Mutation of in serotype 4 (TIGR4) and serotype 6B (BHN418) pneumococcal strains abolishes the ability of the mutants to activate TLR2 signaling. Loss of also led to the concomitant decrease in interferon signaling triggered by the bacterium. However, only BHN418 but not TIGR4 was significantly attenuated in epithelial adherence and microinvasion compared to their respective wild-type strains. To test the hypothesis that differential lipoprotein repertoires in TIGR4 and BHN418 lead to the intraspecies variation in epithelial microinvasion, we employed a motif-based genome analysis and identified an additional 525 a.a. lipoprotein (neumococcal ccessory ipoprotein ; ) encoded by BHN418 that is absent in TIGR4. The gene encoding sits within a putative genetic island present in ~10% of global pneumococcal isolates. While was enriched in the carriage and otitis media pneumococcal strains, neither mutation nor overexpression of the gene encoding this lipoprotein significantly changed microinvasion patterns. In conclusion, mutation of attenuates epithelial inflammatory responses during pneumococcal-epithelial interactions, with intraspecies variation in the effect on microinvasion. Differential lipoprotein repertoires encoded by the different strains do not explain these differences in microinvasion. Rather, we postulate that post-translational modifications of lipoproteins may account for the differences in microinvasion.IMPORTANCE (pneumococcus) is an important mucosal pathogen, estimated to cause over 500,000 deaths annually. Nasopharyngeal colonization is considered a necessary prerequisite for disease, yet many people are transiently and asymptomatically colonized by pneumococci without becoming unwell. It is therefore important to better understand how the colonization process is controlled at the epithelial surface. Controlled human infection studies revealed the presence of pneumococci within the epithelium of healthy volunteers (microinvasion). In this study, we focused on the regulation of epithelial microinvasion by pneumococcal lipoproteins. We found that pneumococcal lipoproteins induce epithelial inflammation but that differing lipoprotein repertoires do not significantly impact the magnitude of microinvasion. Targeting mucosal innate immunity and epithelial microinvasion alongside the induction of an adaptive immune response may be effective in preventing pneumococcal colonization and disease.
Topics: Streptococcus pneumoniae; Humans; Lipoproteins; Epithelial Cells; Pneumococcal Infections; Bacterial Proteins; Toll-Like Receptor 2; Nasopharynx; Mutation; Bacterial Adhesion
PubMed: 38629841
DOI: 10.1128/iai.00447-23