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MBio Mar 2020Environmental exposure has a significant impact on human health. While some airborne fungi can cause life-threatening infections, the impact of environment on fungal...
Environmental exposure has a significant impact on human health. While some airborne fungi can cause life-threatening infections, the impact of environment on fungal spore dispersal and transmission is poorly understood. The democratization of shotgun metagenomics allows us to explore important questions about fungal propagation. We focus on , a genus of host-specific fungi that infect mammals via airborne particles. In humans, causes lethal infections in immunocompromised patients if untreated, although its environmental reservoir and transmission route remain unclear. Here, we attempt to clarify, by analyzing human exposome metagenomic data sets, whether humans are exposed to different species present in the air but only cells are able to replicate or whether they are selectively exposed to Our analysis supports the latter hypothesis, which is consistent with a local transmission model. These data also suggest that healthy carriers are a major driver for the transmission.
Topics: Air Microbiology; DNA, Fungal; Environmental Exposure; Humans; Immunocompromised Host; Metagenomics; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 32156824
DOI: 10.1128/mBio.03138-19 -
Parasitology Research Jan 2019Pneumocystis jirovecii is an opportunistic fungus occurring in human lungs. The group at highest risk consists of HIV-infected and non-HIV-infected immunosuppressed...
Pneumocystis jirovecii is an opportunistic fungus occurring in human lungs. The group at highest risk consists of HIV-infected and non-HIV-infected immunosuppressed individuals. In these patients, P. jirovecii infection may lead to Pneumocystis pneumonia; it may, however, persist also in an asymptomatic form. This study aimed to determine the prevalence of P. jirovecii and potential risk factors for infection in a group of renal transplant recipients and to characterize the genetic diversity of this fungus in the studied population. Sputum specimens from 72 patients were tested for presence of P. jirovecii using immunofluorescence microscopy, as well as nested PCR targeting the mtLSU rRNA gene. Genotyping involving analysis of four loci-mtLSU rRNA, CYB, DHPS, and SOD-was used to characterize the diversity of the detected organisms. Pneumocystis DNA was detected in eight (11.11%) patients. It has been shown that low eosinophil count and dual immunosuppressive treatment combining prednisone and calcineurin inhibitors are potential risk factors for colonization. Analysis of genotype distribution showed an association of the wild-type genotype of mtLSU rRNA with lower average age of patients and shorter time after kidney transplantation. Furthermore, CYB 2 genotype was detected only in patients with the ongoing prophylaxis regimen. In conclusion, renal transplant recipients are at risk of Pneumocystis colonization even a long time after transplantation. The present preliminary study identifies specific polymorphisms that appear to be correlated with certain patient characteristics and highlights the need for deeper investigation of these associations in renal transplant recipients.
Topics: Adult; Aged; Female; Genetic Variation; Genotype; Humans; Immunocompromised Host; Kidney Transplantation; Lung; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Postoperative Complications; Prevalence; Transplant Recipients; Young Adult
PubMed: 30392033
DOI: 10.1007/s00436-018-6131-0 -
MBio May 2018species are opportunistic mammalian pathogens that cause severe pneumonia in immunocompromised individuals. These fungi are highly host specific and uncultivable Human... (Comparative Study)
Comparative Study
species are opportunistic mammalian pathogens that cause severe pneumonia in immunocompromised individuals. These fungi are highly host specific and uncultivable Human infections present major challenges because of a limited therapeutic arsenal and the rise of drug resistance. To investigate the diversity and demographic history of natural populations of infecting humans, rats, and mice, we performed whole-genome and large-scale multilocus sequencing of infected tissues collected in various geographic locations. Here, we detected reduced levels of recombination and variations in historical demography, which shape the global population structures. We report estimates of evolutionary rates, levels of genetic diversity, and population sizes. Molecular clock estimates indicate that species diverged before their hosts, while the asynchronous timing of population declines suggests host shifts. Our results have uncovered complex patterns of genetic variation influenced by multiple factors that shaped the adaptation of populations during their spread across mammals. Understanding how natural pathogen populations evolve and identifying the determinants of genetic variation are central issues in evolutionary biology. , a fungal pathogen which infects mammals exclusively, provides opportunities to explore these issues. In humans, can cause a life-threatening pneumonia in immunosuppressed individuals. In analysis of different species infecting humans, rats, and mice, we found that there are high infection rates and that natural populations maintain a high level of genetic variation despite low levels of recombination. We found no evidence of population structuring by geography. Our comparisons of the times of divergence of these species to their respective hosts suggest that may have undergone recent host shifts. The results demonstrate that strains are widely disseminated geographically and provide a new understanding of the evolution of these pathogens.
Topics: Animals; Genetic Variation; Genomics; Humans; Mice; Phylogeny; Pneumocystis; Pneumonia, Pneumocystis; Rats; Rats, Sprague-Dawley; Recombination, Genetic; Rodent Diseases
PubMed: 29739910
DOI: 10.1128/mBio.00381-18 -
European Journal of Clinical... Oct 2017To understand the epidemiological significance of Pneumocystis detection in a lung tissue sample of non-immunosuppressed individuals, we examined sampling procedures,... (Review)
Review
To understand the epidemiological significance of Pneumocystis detection in a lung tissue sample of non-immunosuppressed individuals, we examined sampling procedures, laboratory methodology, and patient characteristics of autopsy series reported in the literature. Number of tissue specimens, DNA-extraction procedures, age and underlying diagnosis highly influence yield and are critical to understand yield differences of Pneumocystis among reports of pulmonary colonization in immunocompetent individuals.
Topics: Autopsy; Humans; Lung; Microbiological Techniques; Pneumocystis; Pneumonia, Pneumocystis; Specimen Handling
PubMed: 28584896
DOI: 10.1007/s10096-017-3006-8 -
Cellular Microbiology Oct 2020Caspase recruitment domains-containing protein 9 (CARD9) is an adaptor molecule critical for key signalling pathways initiated through C-type lectin receptors (CLRs)....
Caspase recruitment domains-containing protein 9 (CARD9) is an adaptor molecule critical for key signalling pathways initiated through C-type lectin receptors (CLRs). Previous studies demonstrated that Pneumocystis organisms are recognised through a variety of CLRs. However, the role of the downstream CARD9 adaptor signalling protein in host defence against Pneumocystis infection remains to be elucidated. Herein, we analysed the role of CARD9 in host defence against Pneumocystis both in CD4-depleted CARD9 and immunocompetent hosts. Card9 gene-disrupted (CARD9 ) mice were more susceptible to Pneumocystis, as evidenced by reduced fungal clearance in infected lungs compared to wild-type (WT) infected mice. Our data suggests that this defect was due to impaired proinflammatory responses. Furthermore, CARD9 macrophages were severely compromised in their ability to differentiate and express M1 and M2 macrophage polarisation markers, to enhanced mRNA expression for Dectin-1 and Mincle, and most importantly, to kill Pneumocystis in vitro. Remarkably, compared to WT mice, and despite markedly increased organism burdens, CARD9 animals did not exhibit worsened survival during pneumocystis pneumonia (PCP), perhaps related to decreased lung injury due to altered influx of inflammatory cells and decreased levels of proinflammatory cytokines in response to the organism. Finally, although innate phase cytokines were impaired in the CARD9 animals during PCP, T-helper cell cytokines were normal in immunocompetent CARD9 animals infected with Pneumocystis. Taken together, our data demonstrate that CARD9 has a critical function in innate immune responses against Pneumocystis.
Topics: Animals; CARD Signaling Adaptor Proteins; Cell Differentiation; Colony Count, Microbial; Cytokines; Immunocompromised Host; Lectins, C-Type; Lung; Macrophages, Alveolar; Membrane Proteins; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; Peroxidase; Pneumocystis; Pneumocystis carinii; Pneumonia, Pneumocystis; Rats; T-Lymphocytes, Helper-Inducer; Tumor Necrosis Factor-alpha
PubMed: 32548948
DOI: 10.1111/cmi.13235 -
International Journal of Infectious... Sep 2019Histoplasma capsulatum and Pneumocystis jirovecii are respiratory fungal pathogens that principally cause pulmonary disease. Coinfection with both pathogens is scarcely...
BACKGROUND
Histoplasma capsulatum and Pneumocystis jirovecii are respiratory fungal pathogens that principally cause pulmonary disease. Coinfection with both pathogens is scarcely reported. This study detected this coinfection using specific molecular methods for each fungus in the bronchoalveolar lavage (BAL) of patients from a tertiary care hospital.
MATERIALS AND METHODS
BAL samples from 289 hospitalized patients were screened by PCR with specific markers for H. capsulatum (Hcp100) and P. jirovecii (mtLSUrRNA and mtSSUrRNA). The presence of these pathogens was confirmed by the generated sequences for each marker. The clinical and laboratory data for the patients were analyzed using statistical software.
RESULTS
The PCR findings separated three groups of patients, where the first was represented by 60 (20.8%) histoplasmosis patients, the second by 45 (15.6%) patients with pneumocystosis, and the last group by 12 (4.2%) patients with coinfection. High similarity among the generated sequences of each species was demonstrated by BLASTn and neighbor-joining algorithms. The estimated prevalence of H. capsulatum and P. jirovecii coinfection was higher in HIV patients.
Topics: Adult; Aged; Bronchoalveolar Lavage; Coinfection; Female; HIV Infections; Histoplasma; Histoplasmosis; Humans; Male; Mexico; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Tertiary Care Centers
PubMed: 31207386
DOI: 10.1016/j.ijid.2019.06.010 -
Emerging Infectious Diseases Oct 2021Prophylactic trimethoprim/sulfamethoxazole (TMP/SMX) prevents Pneumocystis jirovecii pneumonia and nocardiosis in immunocompromised patients but sometimes is avoided...
Prophylactic trimethoprim/sulfamethoxazole (TMP/SMX) prevents Pneumocystis jirovecii pneumonia and nocardiosis in immunocompromised patients but sometimes is avoided because of purported allergies or side effects. Of 25 immunocompromised patients receiving alternative prophylaxis in whom nocardiosis developed, 16 subsequently tolerated TMP/SMX treatment. Clinicians should consider TMP/SMX allergy evaluation and rechallenging to assess patient tolerance.
Topics: Humans; Immunocompromised Host; Nocardia Infections; Pneumocystis; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies
PubMed: 34545802
DOI: 10.3201/eid2710.210620 -
Journal of Clinical Microbiology Aug 1990Pulsed-field gel electrophoresis techniques were used to examine the chromosomes of Pneumocystis carinii isolated from laboratory rats and two human subjects. P. carinii...
Pulsed-field gel electrophoresis techniques were used to examine the chromosomes of Pneumocystis carinii isolated from laboratory rats and two human subjects. P. carinii organisms isolated from each of four rat colonies and from two patients each produced a distinct band pattern, but in all cases the bands ranged in size from 300 to 700 kilobase pairs. P. carinii from three rat colonies produced patterns containing 15 prominent bands. Of these 15 bands, 2 stained more intensely than would be expected of bands of their size, suggesting that the P. carinii haploid genome contains 17 to 19 chromosomes. Summing the molecular sizes of the bands and accounting for staining intensities suggested that the haploid genome of rat-derived P. carinii contains on the order of 10(7) base pairs. Human-derived P. carinii produced patterns containing 10 to 12 bands which appeared to be similar to the 15-band patterns seen in rat-derived P. carinii with respect to the size range of the bands. P. carinii from the fourth rat colony produced a more complex band pattern containing approximately 22 bands, most of which appeared to comigrate with the bands present in one of the 15-band P. carinii patterns, suggesting that these animals were simultaneously infected by two different varieties of P. carinii. Hybridization experiments using oligonucleotide probes specific for the P. carinii 18S rRNA gene supported this possibility. The band pattern of P. carinii derived from a given rat colony was generally stable over time. P. carinii band patterns were not strictly rat strain specific and appeared to be transferrable between animals housed in the same room.
Topics: Animals; Chromosomes, Fungal; DNA, Fungal; Electrophoresis; Genetic Variation; Humans; Karyotyping; Male; Molecular Weight; Pneumocystis; Pneumonia, Pneumocystis; Polymorphism, Restriction Fragment Length; RNA, Ribosomal, 18S; Rats; Rats, Inbred Strains; Repetitive Sequences, Nucleic Acid; United States
PubMed: 1975595
DOI: 10.1128/jcm.28.8.1785-1795.1990 -
Infection and Immunity Mar 2017We explored differential polarization of macrophages during infection using a rat model of pneumonia. We observed enhanced pulmonary M1 macrophage polarization in...
We explored differential polarization of macrophages during infection using a rat model of pneumonia. We observed enhanced pulmonary M1 macrophage polarization in immunosuppressed (IS) hosts, but an M2 predominant response in immunocompetent (IC) hosts following challenge. Increased inflammation and inducible nitric oxide synthase (iNOS) levels characterized the M1 response. However, macrophage ability to produce nitric oxide was defective. In contrast, the lungs of IC animals revealed a prominent M2 gene signature, and these macrophages effectively elicited an oxidative burst associated with clearance of In addition, during infection the expression of Dectin-1, a critical receptor for recognition and clearance of , was upregulated in macrophages of IC animals but suppressed in IS animals. In the absence of an appropriate cytokine milieu for M2 differentiation, induced an M1 response both and The M1 response induced by was plastic in nature and reversible with appropriate cytokine stimuli. Finally, we tested whether macrophage polarization can be modulated and used to help manage the pathogenesis of pneumonia by adoptive transfer. Treatment with both M1 and M2 cells significantly improved survival of -infected IS hosts. However, M2 treatment provided the best outcomes with efficient clearance of and reduced inflammation.
Topics: Adoptive Transfer; Animals; Disease Models, Animal; Female; Gene Expression Profiling; Gene Expression Regulation; Immunocompromised Host; Lectins, C-Type; Macrophage Activation; Macrophages, Alveolar; Mortality; Pneumocystis; Pneumonia, Pneumocystis; Rats
PubMed: 27993972
DOI: 10.1128/IAI.00939-16 -
MBio Jun 2018
Topics: DNA, Fungal; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Respiratory System
PubMed: 29895638
DOI: 10.1128/mBio.00939-18