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The Lancet. Microbe Oct 2023
Topics: Humans; Mycoplasma pneumoniae; Pneumonia, Mycoplasma
PubMed: 37393927
DOI: 10.1016/S2666-5247(23)00182-9 -
The Lancet. Microbe Feb 2024
Topics: Humans; Mycoplasma pneumoniae; COVID-19; Pandemics; Pneumonia, Mycoplasma; Anti-Bacterial Agents
PubMed: 38008103
DOI: 10.1016/S2666-5247(23)00344-0 -
Emerging Microbes & Infections Dec 2023Although previous studies have reported the dysregulation of respiratory tract microbiota in infectious diseases, insufficient data exist regarding respiratory...
Although previous studies have reported the dysregulation of respiratory tract microbiota in infectious diseases, insufficient data exist regarding respiratory microbiota imbalances in the lower respiratory tracts (LRTs) of children with pneumonia (MPP). Here, we analysed the microbial community using 16S rRNA gene sequencing. Finally, bronchoalveolar lavage fluid (BALF) samples from 158 children with MPP and 29 with bacterial or viral pneumonia (control group) were collected. The diversity of the microbial community was significantly different between the two groups. A significantly increased abundance of Tenericutes and was detected in the MPP group, exceeding 67% and 65% of the total bacterial population, respectively. Using abundance as the diagnostic method, the sensitivity and specificity of the model was 97.5% and 96.6%, respectively. Compared to the mild MPP group, lower alpha diversity and significantly increased abundance were found in the severe MPP group (< 0.01). The abundance of was positively correlated with complications and clinical indices in children with severe MPP compared with children with mild MPP. Our study describes the features of the LRT microbiota of children with MPP and uncovered its association with disease severity. This finding may offer insights into the pathogenesis of MPP in children.
Topics: Humans; Child; Mycoplasma pneumoniae; RNA, Ribosomal, 16S; Pneumonia, Mycoplasma; Bronchoalveolar Lavage Fluid; Microbiota
PubMed: 37132354
DOI: 10.1080/22221751.2023.2202272 -
Nature Aug 2023Possessing only essential genes, a minimal cell can reveal mechanisms and processes that are critical for the persistence and stability of life. Here we report on how an... (Comparative Study)
Comparative Study
Possessing only essential genes, a minimal cell can reveal mechanisms and processes that are critical for the persistence and stability of life. Here we report on how an engineered minimal cell contends with the forces of evolution compared with the Mycoplasma mycoides non-minimal cell from which it was synthetically derived. Mutation rates were the highest among all reported bacteria, but were not affected by genome minimization. Genome streamlining was costly, leading to a decrease in fitness of greater than 50%, but this deficit was regained during 2,000 generations of evolution. Despite selection acting on distinct genetic targets, increases in the maximum growth rate of the synthetic cells were comparable. Moreover, when performance was assessed by relative fitness, the minimal cell evolved 39% faster than the non-minimal cell. The only apparent constraint involved the evolution of cell size. The size of the non-minimal cell increased by 80%, whereas the minimal cell remained the same. This pattern reflected epistatic effects of mutations in ftsZ, which encodes a tubulin-homologue protein that regulates cell division and morphology. Our findings demonstrate that natural selection can rapidly increase the fitness of one of the simplest autonomously growing organisms. Understanding how species with small genomes overcome evolutionary challenges provides critical insights into the persistence of host-associated endosymbionts, the stability of streamlined chassis for biotechnology and the targeted refinement of synthetically engineered cells.
Topics: Biotechnology; Cell Division; Evolution, Molecular; Genome, Bacterial; Mutation; Mycoplasma mycoides; Genes, Essential; Synthetic Biology; Cell Size; Epistasis, Genetic; Selection, Genetic; Genetic Fitness; Symbiosis; Tubulin
PubMed: 37407813
DOI: 10.1038/s41586-023-06288-x -
The Clinical Respiratory Journal Jul 2023To compare the demographic and clinical features, laboratory and imaging findings in mycoplasma pneumoniae pneumonia (MPP) children with non-MPP (NMPP) children and...
BACKGROUND
To compare the demographic and clinical features, laboratory and imaging findings in mycoplasma pneumoniae pneumonia (MPP) children with non-MPP (NMPP) children and general MPP (GMPP) children with refractory MPP (RMPP) children and analysis the relationship with the severity of disease.
METHODS
The study included 265 children with MPP and 230 children with NMPP in the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University from 2020 to 2021. The children with MPP included RMPP (n = 85) and GMPP (n = 180). Demographic and clinical characteristics, laboratory and imaging findings of all children were measured as baseline data within 24 h after admission and the differences between MPP and NMPP, RMPP and GMPP patients were compared. ROC curves were used to evaluate the diagnostic and predictive value of different indicators for RMPP.
RESULTS
Fever duration and hospital stay in children with MPP were longer than those with NMPP. The number of patients with imaging features of pleural effusion, lung consolidation and bronchopneumonia in MPP group was significantly higher than that in NMPP group. Compared with NMPP group, the levels of C-reactive protein (CRP), procalcitonin (PCT), serum amyloid A (SAA), erythrocyte sedimentation rate (ESR), lactic dehydrogenase (LDH), prothrombin time (PT), fibrinogen (FIB) and D-dimer and inflammatory cytokines (interleukin [IL]-6, IL-8, IL-10 and IL-1β) in MPP group were significantly higher (P < 0.05). The clinical symptoms and pulmonary imaging findings were more severe in RMPP group. The levels of white blood cell (WBC), CRP, PCT, SAA, ESR, alanine aminotransferase (ALT), LDH, ferritin, PT, FIB, D-dimer and inflammatory cytokines in RMPP group were higher than those in GMPP group. There was no significant difference in the level of lymphocyte subsets between the RMPP and GMPP group. IL-6, IL-10, LDH, PT, D-dimer and lung consolidation were independent risk factors for RMPP. IL-6 levels and LDH activity were good predictors of RMPP.
CONCLUSION
In conclusion, there were differences in clinical characteristics and serum inflammatory markers between MPP group and NMPP group, RMPP group and GMPP group. IL-6, IL-10, LDH, PT and D-dimer can be used as predictive indicators for RMPP.
Topics: Humans; Child; Pneumonia, Mycoplasma; Interleukin-10; Interleukin-6; Retrospective Studies; Biomarkers; Mycoplasma pneumoniae; C-Reactive Protein; Cytokines; Procalcitonin
PubMed: 37142438
DOI: 10.1111/crj.13620 -
The Lancet. Microbe Jun 2024
Topics: Humans; China; Pneumonia, Mycoplasma; Macrolides; Mycoplasma pneumoniae; Anti-Bacterial Agents; Drug Resistance, Bacterial
PubMed: 38244553
DOI: 10.1016/S2666-5247(23)00405-6 -
Frontiers in Immunology 2023CC16 (Club Cell Secretory Protein) is a protein produced by club cells and other non-ciliated epithelial cells within the lungs. CC16 has been shown to protect against...
RATIONALE
CC16 (Club Cell Secretory Protein) is a protein produced by club cells and other non-ciliated epithelial cells within the lungs. CC16 has been shown to protect against the development of obstructive lung diseases and attenuate pulmonary pathogen burden. Despite recent advances in understanding CC16 effects in circulation, the biological mechanisms of CC16 in pulmonary epithelial responses have not been elucidated.
OBJECTIVES
We sought to determine if CC16 deficiency impairs epithelial-driven host responses and identify novel receptors expressed within the pulmonary epithelium through which CC16 imparts activity.
METHODS
We utilized mass spectrometry and quantitative proteomics to investigate how CC16 deficiency impacts apically secreted pulmonary epithelial proteins. Mouse tracheal epithelial cells (MTECS), human nasal epithelial cells (HNECs) and mice were studied in naïve conditions and after Mp challenge.
MEASUREMENTS AND MAIN RESULTS
We identified 8 antimicrobial proteins significantly decreased by CC16 MTECS, 6 of which were validated by mRNA expression in Severe Asthma Research Program (SARP) cohorts. Short Palate Lung and Nasal Epithelial Clone 1 (SPLUNC1) was the most differentially expressed protein (66-fold) and was the focus of this study. Using a combination of MTECs and HNECs, we found that CC16 enhances pulmonary epithelial-driven SPLUNC1 expression via signaling through the receptor complex Very Late Antigen-2 (VLA-2) and that rCC16 given to mice enhances pulmonary SPLUNC1 production and decreases (Mp) burden. Likewise, rSPLUNC1 results in decreased Mp burden in mice lacking CC16 mice. The VLA-2 integrin binding site within rCC16 is necessary for induction of SPLUNC1 and the reduction in Mp burden.
CONCLUSION
Our findings demonstrate a novel role for CC16 in epithelial-driven host defense by up-regulating antimicrobials and define a novel epithelial receptor for CC16, VLA-2, through which signaling is necessary for enhanced SPLUNC1 production.
Topics: Animals; Humans; Mice; Asthma; Integrin alpha2beta1; Lung; Mycoplasma pneumoniae; Signal Transduction
PubMed: 38053993
DOI: 10.3389/fimmu.2023.1277582 -
Clinical Infectious Diseases : An... Nov 2023Mycoplasma genitalium (MG) is on the CDC Watch List of Antimicrobial Resistance Threats, yet there is no systematic surveillance to monitor change.
BACKGROUND
Mycoplasma genitalium (MG) is on the CDC Watch List of Antimicrobial Resistance Threats, yet there is no systematic surveillance to monitor change.
METHODS
We initiated surveillance in sexual health clinics in 6 cities, selecting a quota sample of urogenital specimens tested for gonorrhea and/or chlamydia. We abstracted patient data from medical records and detected MG and macrolide-resistance mutations (MRMs) by nucleic acid amplification testing. We used Poisson regression to estimate adjusted prevalence ratios (aPRs) and 95% CIs, adjusting for sampling criteria (site, birth sex, symptom status).
RESULTS
From October-December 2020 we tested 1743 urogenital specimens: 57.0% from males, 46.1% from non-Hispanic Black persons, and 43.8% from symptomatic patients. MG prevalence was 16.6% (95% CI: 14.9-18.5%; site-specific range: 9.9-23.5%) and higher in St Louis (aPR: 1.9; 1.27-2.85), Greensboro (aPR: 1.8; 1.18-2.79), and Denver (aPR: 1.7; 1.12-2.44) than Seattle. Prevalence was highest in persons <18 years (30.4%) and declined 3% per each additional year of age (aPR: .97; .955-.982). MG was detected in 26.8%, 21.1%, 11.8%, and 15.4% of urethritis, vaginitis, cervicitis, and pelvic inflammatory disease (PID), respectively. It was present in 9% of asymptomatic males and 15.4% of asymptomatic females, and associated with male urethritis (aPR: 1.7; 1.22-2.50) and chlamydia (aPR: 1.7; 1.13-2.53). MRM prevalence was 59.1% (95% CI: 53.1-64.8%; site-specific range: 51.3-70.6%). MRMs were associated with vaginitis (aPR: 1.8; 1.14-2.85), cervicitis (aPR: 3.5; 1.69-7.30), and PID cervicitis (aPR: 1.8; 1.09-3.08).
CONCLUSIONS
MG infection is common in persons at high risk of sexually transmitted infections; testing symptomatic patients would facilitate appropriate therapy. Macrolide resistance is high and azithromycin should not be used without resistance testing.
Topics: Female; Humans; Male; Anti-Bacterial Agents; Urethritis; Mycoplasma genitalium; Uterine Cervicitis; Sexual Health; Macrolides; Drug Resistance, Bacterial; Pelvic Inflammatory Disease; Vaginitis; Mycoplasma Infections; Prevalence
PubMed: 37402645
DOI: 10.1093/cid/ciad405 -
International Journal of Medical... Sep 2023Mycoplasma pneumoniae (MP) is one of the main pathogens causing community acquired pneumonia (CAP) in children and adults. Previous pharmacological and clinical studies...
Mycoplasma pneumoniae (MP) is one of the main pathogens causing community acquired pneumonia (CAP) in children and adults. Previous pharmacological and clinical studies have shown that Polydatin (PD) exerts anti-inflammatory action by conferring protective benefit in MP pneumonia. However, the mechanism underlying the of PD on MP infection remains unclear. It was found that PD alleviated MP-induced injury by inhibiting caspase-1/gasdermin D (GSDMD)-mediated epithelial pyroptosis. The results demonstrated that PD inhibited the transformation of GSDMD to N-terminal gasdermin-N (GSDMD-N) by decreasing caspase-1 activation, as well as suppressed the formation and secretion of interleukin-1β (IL-1β) and interleukin-18 (IL-18), reversed Na, K-ATPase reduction, and suppressed LDH release both in vitro and vivo. Taken together, epithelial pyroptosis in BEAS-2B cells and lung injury in mice were prevented by PD. In conclusion, PD suppressed pulmonary injury triggered by MP infection, by inhibiting the caspase-1/GSDMD-mediated epithelial pyroptosis signaling pathway. Thus, PD may be regarded as a potential therapy for MP-induced inflammation.
Topics: Humans; Child; Animals; Mice; Caspase 1; Mycoplasma pneumoniae; Intracellular Signaling Peptides and Proteins; Pyroptosis; Gasdermins; Pneumonia, Mycoplasma; Phosphate-Binding Proteins; Pore Forming Cytotoxic Proteins
PubMed: 37776814
DOI: 10.1016/j.ijmm.2023.151586 -
Medicine Jul 2023This study aimed to evaluate the diagnostic value of chemiluminescence immunoassay (CLIA), passive particle agglutination (PPA), and indirect immunofluorescence assay...
This study aimed to evaluate the diagnostic value of chemiluminescence immunoassay (CLIA), passive particle agglutination (PPA), and indirect immunofluorescence assay (IFA) in detecting Mycoplasma pneumoniae infection in children. Serum samples from 165 children with acute community-acquired respiratory tract infections were examined using CLIA, PPA, and IFA, and consistency coefficient, specificity, and sensitivity were analyzed. Compared with the PPA (titer ≥ 1:160), the consistency coefficients of the immunoglobulin(Ig)M-CLIA, immunoglobulin(Ig)G-CLIA and IgM-IFA methods were 93.94%, 75.76%, and 83.64%, respectively. The positive likelihood ratio (PLR) and specificity of IgM-CLIA was 19.40 and 95.49%, respectively. The consistency coefficient of (IgM+IgG)-CLIA and PPA (titer ≥ 1:160) was 89.1%, and the sensitivity and negative predictive value of (IgM+IgG)-CLIA were 96.88% and 98.94%, respectively. CLIA MP-IgM has high concordance with PPA, and its specificity and sensitivity are higher than those of CLIA MP-IgG and IFA MP-IgM, suggesting its better diagnosis of early MP infection. The sensitivity and negative predictive value of CLIA MP (IgM+IgG) were higher than those of PPA or IFA, indicating that it should be considered as a priority in the diagnosis of MP infection.
Topics: Humans; Child; Mycoplasma pneumoniae; Immunoglobulin M; Immunoglobulin G; Antibodies, Bacterial; Pneumonia, Mycoplasma; Serologic Tests; Respiratory Tract Infections; Community-Acquired Infections
PubMed: 37478238
DOI: 10.1097/MD.0000000000034133