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Journal of the Association of Medical... Dec 2021is an obligate intracellular bacterium usually found as a commensal in the human oral cavity. Symptomatic infections with this organism are rare, but severe disease has...
is an obligate intracellular bacterium usually found as a commensal in the human oral cavity. Symptomatic infections with this organism are rare, but severe disease has been described in the setting of impaired humoral immunity. Here, we describe a case in which was identified from the joint fluid of a patient with septic arthritis, splenic lesions, and agammaglobulinemia. A 15-year-old boy was admitted to the hospital with fever, progressive left knee swelling, and pain. His medical history was significant for Burkitt's lymphoma, the treatment of which had included rituximab 6 years earlier. was identified in the synovial fluid using 16S ribosomal RNA gene sequencing. He was also found to be hypogammaglobulinemic, and imaging revealed multiple splenic lesions. He was treated with doxycycline and intravenous immunoglobulin, which resulted in complete resolution of his arthritis and other symptoms. species should be suspected in patients with humoral immunodeficiency and compatible findings.
PubMed: 36338458
DOI: 10.3138/jammi-2021-0002 -
Open Forum Infectious Diseases Sep 2022is a rare cause of invasive infection in immunodeficient hosts. Phosphatidylinositol 3-kinase, regulatory subunit 1 () mutations predispose patients to sinopulmonary...
is a rare cause of invasive infection in immunodeficient hosts. Phosphatidylinositol 3-kinase, regulatory subunit 1 () mutations predispose patients to sinopulmonary infections, alongside bronchiectasis autoimmunity and lymphoproliferation. We report 2 cases of deficiency with invasive and effective treatment options.
PubMed: 36196300
DOI: 10.1093/ofid/ofac472 -
Journal of Thoracic Disease Feb 2022The current COVID-19 pandemic is posing a major challenge to public health on a global scale. While it is generally believed that severe COVID-19 results from...
BACKGROUND
The current COVID-19 pandemic is posing a major challenge to public health on a global scale. While it is generally believed that severe COVID-19 results from over-expression of inflammatory mediators (i.e., a "cytokine storm"), it is still unclear whether and how co-infecting pathogens contribute to disease pathogenesis. To address this, we followed the entire course of the disease in cases with severe or critical COVID-19 to determine the presence and abundance of all potential pathogens present-the total "infectome"-and how they interact with the host immune system in the context of severe COVID-19.
METHODS
We examined one severe and three critical cases of COVID-19, as well as a set of healthy controls, with longitudinal samples (throat swab, whole blood, and serum) collected from each case. Total RNA sequencing (meta-transcriptomics) was performed to simultaneously investigate pathogen diversity and abundance, as well as host immune responses, in each sample. A Bio-Plex method was used to measure serum cytokine and chemokine levels.
RESULTS
Eight pathogens, SARS-CoV-2, (), (), (), (), , herpes simplex virus (HSV) and human cytomegalovirus (CMV), identified in patients with COVID-19 appeared at different stages of the disease. The dynamics of inflammatory mediators in serum and the respiratory tract were more strongly associated with the dynamics of the infectome compared with SARS-CoV-2 alone. Correlation analysis revealed that pulmonary injury was directly associated with cytokine levels, which in turn were associated with the proliferation of SARS-CoV-2 and co-infecting pathogens.
CONCLUSIONS
For each patient, the cytokine storm that resulted in acute lung injury and death involved a dynamic and highly complex infectome, of which SARS-CoV-2 was a component. These results indicate the need for a precision medicine approach to investigate both the infection and host response as a standard means of infectious disease characterization.
PubMed: 35280492
DOI: 10.21037/jtd-21-1284 -
International Journal of Cancer Mar 2022Colonization of specific bacteria in the human mouth was reported to be associated with gastric cancer risk. However, previous studies were limited by retrospective...
Colonization of specific bacteria in the human mouth was reported to be associated with gastric cancer risk. However, previous studies were limited by retrospective study designs and low taxonomic resolutions. We performed a prospective case-control study nested within three cohorts to investigate the relationship between oral microbiome and gastric cancer risk. Shotgun metagenomic sequencing was employed to characterize the microbiome in prediagnostic buccal samples from 165 cases and 323 matched controls. Associations of overall microbial richness and abundance of microbial taxa, gene families and metabolic pathways with gastric cancer risk were evaluated via conditional logistic regression. Analyses were performed within each cohort, and results were combined by meta-analyses. We found that overall microbial richness was associated with decreased gastric cancer risk, with an odds ratio (OR) per standard deviation (SD) increase in Simpson's reciprocal index of 0.77 (95% confidence interval [CI] = 0.61-0.99). Nine taxa, 38 gene families and six pathways also showed associations with gastric cancer risk at P < .05. Neisseria mucosa and Prevotella pleuritidis were enriched, while Mycoplasma orale and Eubacterium yurii were depleted among cases with ORs and 95% CIs per SD increase in centered log-ratio transformed taxa abundance of 1.31 (1.03-1.67), 1.26 (1.00-1.57), 0.74 (0.59-0.94) and 0.80 (0.65-0.98), respectively. The top two gene families (P = 3.75 × 10 and 3.91 × 10 ) and pathways (P = 1.75 × 10 and 1.53 × 10 ) associated with gastric cancer were related to the decreased risk and are involved in hexitol metabolism. Our study supports the hypothesis that oral microbiota may play a role in gastric cancer etiology.
Topics: Adult; Black or African American; Aged; Asian People; Female; Gastrointestinal Microbiome; Humans; Male; Metabolic Networks and Pathways; Middle Aged; Mouth; Prospective Studies; Risk; Stomach Neoplasms; White People
PubMed: 34664266
DOI: 10.1002/ijc.33847 -
Diagnostics (Basel, Switzerland) May 2021, , and sp. are atypical bacteria responsible for in vitro cell culture contaminations that can warp the results. These bacteria also cause human and animal infections...
, , and sp. are atypical bacteria responsible for in vitro cell culture contaminations that can warp the results. These bacteria also cause human and animal infections and may lead to chronic diseases. In developed polymerase chain reaction (PCR) in this study a quantitative PCR with SYBR Green I fluorochrome was applied to facilitate the , , and sp. DNA detection and identification. Screening Test-1 v.1 (triplex qPCR) allowed for the detection of 11 species. Test-1 v.2 (three single qPCRs) pre-identified three subgroups, allowing for the reduction of using single qPCRs in Test-2 for species identification. The range of both tests was consistent with pharmacopeial requirements for microbial quality control of mammal cells and included detection of , , , , , , , , , , and . Limit of detection values varied between 125-300 and 50-100 number of copies per milliliter in Test-1 and Test-2, respectively. Test-1 and Test-2 showed fully concordant results, allowed for time-saving detection and/or identification of selected species from , , and in tested cell cultures.
PubMed: 34068904
DOI: 10.3390/diagnostics11050876 -
Cell Discovery Apr 2021Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus disease 2019 (COVID-19). However, the microbial composition of...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus disease 2019 (COVID-19). However, the microbial composition of the respiratory tract and other infected tissues as well as their possible pathogenic contributions to varying degrees of disease severity in COVID-19 patients remain unclear. Between 27 January and 26 February 2020, serial clinical specimens (sputum, nasal and throat swab, anal swab and feces) were collected from a cohort of hospitalized COVID-19 patients, including 8 mildly and 15 severely ill patients in Guangdong province, China. Total RNA was extracted and ultra-deep metatranscriptomic sequencing was performed in combination with laboratory diagnostic assays. We identified distinct signatures of microbial dysbiosis among severely ill COVID-19 patients on broad spectrum antimicrobial therapy. Co-detection of other human respiratory viruses (including human alphaherpesvirus 1, rhinovirus B, and human orthopneumovirus) was demonstrated in 30.8% (4/13) of the severely ill patients, but not in any of the mildly affected patients. Notably, the predominant respiratory microbial taxa of severely ill patients were Burkholderia cepacia complex (BCC), Staphylococcus epidermidis, or Mycoplasma spp. (including M. hominis and M. orale). The presence of the former two bacterial taxa was also confirmed by clinical cultures of respiratory specimens (expectorated sputum or nasal secretions) in 23.1% (3/13) of the severe cases. Finally, a time-dependent, secondary infection of B. cenocepacia with expressions of multiple virulence genes was demonstrated in one severely ill patient, which might accelerate his disease deterioration and death occurring one month after ICU admission. Our findings point to SARS-CoV-2-related microbial dysbiosis and various antibiotic-resistant respiratory microbes/pathogens in hospitalized COVID-19 patients in relation to disease severity. Detection and tracking strategies are needed to prevent the spread of antimicrobial resistance, improve the treatment regimen and clinical outcomes of hospitalized, severely ill COVID-19 patients.
PubMed: 33850111
DOI: 10.1038/s41421-021-00257-2 -
Case Reports in Infectious Diseases 2020A young woman with mixed connective tissue disease complicated by erosive arthritis, secondary hypogammaglobulinemia due to rituximab, and a history of many infectious...
A young woman with mixed connective tissue disease complicated by erosive arthritis, secondary hypogammaglobulinemia due to rituximab, and a history of many infectious complications developed multiple nonhealing wounds, polyarticular joint pain, and leukocytosis. Radiographic studies demonstrated multiple scattered areas of osteomyelitis and complex abscesses. Purulent fluid drained from multiple sites did not yield a microbiologic diagnosis by standard culture technique, but was ultimately identified using 16 S ribosomal RNA gene amplification and sequencing. We describe this unique case and review the literature.
PubMed: 32850161
DOI: 10.1155/2020/8852115 -
Antibiotics (Basel, Switzerland) Aug 2019Mycoplasma contamination detrimentally affects cellular functions and the growth of intracellular pathogens in cell cultures. Although several mycoplasmacidal agents are...
Mycoplasma contamination detrimentally affects cellular functions and the growth of intracellular pathogens in cell cultures. Although several mycoplasmacidal agents are commercially available for sterile cell cultures, they are not applicable to rickettsia-infected cells. In our attempt to find an anti-mycoplasma drug for contaminated rickettsial cultures, we determined the susceptibilities of three common species to daptomycin. and showed low-level resistance to daptomycin (minimum inhibitory concentration, MIC = 2 mg/L), whereas was high-level resistant (MIC = 32 mg/L). However, some isolates developed higher resistance to daptomycin after failed treatments with inadequate doses or durations. An aminoglycoside (gentamicin) was still active against and could be used in cultures. For complete eradication of mycoplasmas in cultures, we recommend a 3-week treatment with daptomycin at 256 mg/L. In contaminated cultures, daptomycin at 32 mg/L was effective in eradicating , whereas either gentamicin or amikacin (100 mg/L) was effective in eradicating . Unlike each drug alone, the combinations of daptomycin plus clindamycin and/or quinupristin/dalfopristin proved effective in eradicating . In summary, our study demonstrated the in vitro anti-mycoplasma activity of daptomycin and its application as a new mycoplasma decontamination method for and cultures.
PubMed: 31438510
DOI: 10.3390/antibiotics8030123 -
Applied and Environmental Microbiology Sep 2015Nucleic acid amplification technique (NAT)-based assays (referred to here as NAT assays) are increasingly used as an alternative to culture-based approaches for the...
Nucleic acid amplification technique (NAT)-based assays (referred to here as NAT assays) are increasingly used as an alternative to culture-based approaches for the detection of mycoplasma contamination of cell cultures. Assay features, like the limit of detection or quantification, vary widely between different mycoplasma NAT assays. Biological reference materials may be useful for harmonization of mycoplasma NAT assays. An international feasibility study included lyophilized preparations of four distantly related mycoplasma species (Acholeplasma laidlawii, Mycoplasma fermentans, M. orale, M. pneumoniae) at different concentrations which were analyzed by 21 laboratories using 26 NAT assays with a qualitative, semiquantitative, or quantitative design. An M. fermentans preparation was shown to decrease the interassay variation when used as a common reference material. The preparation was remanufactured and characterized in a comparability study, and its potency (in NAT-detectable units) across different NATs was determined. The World Health Organization (WHO) Expert Committee on Biological Standardization (ECBS) established this preparation to be the "1st World Health Organization international standard for mycoplasma DNA for nucleic acid amplification technique-based assays designed for generic mycoplasma detection" (WHO Tech Rep Ser 987:42, 2014) with a potency of 200,000 IU/ml. This WHO international standard is now available as a reference preparation for characterization of NAT assays, e.g., for determination of analytic sensitivity, for calibration of quantitative assays in a common unitage, and for defining regulatory requirements in the field of mycoplasma testing.
Topics: DNA, Bacterial; Laboratories; Mycoplasma; Nucleic Acid Amplification Techniques; World Health Organization
PubMed: 26070671
DOI: 10.1128/AEM.01150-15 -
Journal of Oral Pathology & Medicine :... Feb 2015Mycoplasmas are the smallest free-living organisms; Mycoplasma salivarium and Mycoplasma orale are the most common species isolated from the oropharynx. Oral leukoplakia...
BACKGROUND
Mycoplasmas are the smallest free-living organisms; Mycoplasma salivarium and Mycoplasma orale are the most common species isolated from the oropharynx. Oral leukoplakia is the most prevalent potentially malignant disorder of the oral mucosa; its etiology has not been defined. Our previous study with DNA-binding fluorescent dye suggested the presence of mycoplasmas in the epithelial cells of leukoplakia tissue.
OBJECTIVE
Our aim was to detect M. salivarium in the epithelial cells of leukoplakia by immunohistochemistry.
DESIGN
We produced a polyclonal antibody (PAb) reactive to Mycoplasma by injecting a rabbit with M. salivarium cells (ATCC 23064) mixed with complete Freund's adjuvant and a monoclonal antibody specific to M. salivarium by injecting M. salivarium cells (ATCC 23557) mixed with complete Freund's adjuvant into the footpads of a rat. Then, we attempted to detect M. salivarium in the epithelium of leukoplakia tissues by immunohistochemistry.
RESULTS
We obtained an antimycoplasma rabbit PAb reactive to all seven Mycoplasma species used in this study. Three hybridoma clones producing monoclonal antibodies specific to M. salivarium were obtained, and an M. salivarium-specific monoclonal antibody, designated 7-6H, was established. Immunohistochemistry with these antibodies revealed M. salivarium in the epithelial cells of leukoplakia with hyperplasia and hyperkeratosis on histology. PCR and sequencing verified the presence of M. salivarium DNA in the epithelial cells of leukoplakia.
CONCLUSION
Intracellular M. salivarium was identified in the epithelial cells of leukoplakia.
Topics: Adult; Aged; Aged, 80 and over; Animals; Antibodies, Bacterial; Antibodies, Monoclonal; Antibody Specificity; Bacteriological Techniques; Chlorocebus aethiops; Epithelial Cells; Female; Fluorescent Antibody Technique; Freund's Adjuvant; Humans; Immunohistochemistry; Intracellular Space; Leukoplakia, Oral; Male; Microscopy, Immunoelectron; Middle Aged; Mouth Mucosa; Mycoplasma salivarium; Polymerase Chain Reaction; Rabbits; Rats; Vero Cells; Young Adult
PubMed: 25065471
DOI: 10.1111/jop.12215