Growth and Airborne Transmission of Cell-Sorted Life Cycle Stages of Pneumocystis carinii

Martinez, Anna; Halliez, Marie C. M.; Aliouat, El Moukhtar; Chabé, Magali; Standaert-Vitse, Annie; Fréalle, Émilie; Gantois, Nausicâa; Pottier, Muriel; Pinon, Anthony; Dei‐Cas, Eduardo; Aliouat-Denis, Cécile-Marie

doi:10.1371/journal.pone.0079958

Cited by 30 publications

(26 citation statements)

References 30 publications

(62 reference statements)

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“…Consequently, it is likely that CAS is useful only if used in combination with another therapy targeting trophic forms, or both cellular forms such as cotrimoxazole. CAS inhibited efficiently the dissemination of the pathogen in animal models (26), which is consistent with the fact that asci are believed to be the transmission particles (26, 50). This feature of CAS might prove useful in the management of infected and susceptible patients within the hospital by inhibiting interhuman transmission of P. jirovecii .…”

Section: Discussionsupporting

confidence: 80%

Site-directed mutagenesis of the 1,3-β glucan synthase catalytic subunit ofPneumocystis jiroveciiand susceptibility assays suggest its sensitivity to caspofungin

Luraschi

Richard

Hauser

2018

Preprint

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The echinocandin caspofungin inhibits the catalytic subunit Gsc1 of the enzymatic complex synthetizing 1,3-β glucan, an essential compound of the fungal wall. Studies in rodents showed that caspofungin can treat Pneumocystis infections. However, its efficacy against Pneumocystis jirovecii, the species infecting exclusively humans, remains controversial. The aim of this study was to assess the sensitivity to caspofungin of the P. jirovecii Gsc1 subunit, as well as of those of Pneumocystis carinii and Pneumocystis murina infecting respectively rats and mice. In absence of an established in vitro culture method for Pneumocystis species, we used functional complementation of the Saccharomyces cerevisiae gsc1 deletant. In the fungal pathogen Candida albicans, mutations leading to amino acid substitutions in Gsc1 confer resistance to caspofungin. We introduced the corresponding mutations into the Pneumocystis gsc1 genes using site-directed mutagenesis. In spot dilution tests, the sensitivity to caspofungin of the complemented strains decreased with the number of mutations introduced, suggesting that the wild-type enzymes are sensitive. The minimum inhibitory concentrations of caspofungin determined by E-test® and Yeastone® for strains complemented with Pneumocystis enzymes (respectively 0.125 and 0.12 microg/ml) were identical to those upon complementation with the enzyme of C. albicans that is sensitive to caspofungin. However, they were lower than the MICs upon complementation with the enzyme of the resistant species Candida parapsilosis (0.19 and 0.25). Sensitivity levels of Gsc1 enzymes of the three Pneumocystis species were similar. Our results suggest that P. jirovecii is sensitive to caspofungin during infections, as P. carinii and P. murina.

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Section: Discussionsupporting

confidence: 80%

Site-directed mutagenesis of the 1,3-β glucan synthase catalytic subunit ofPneumocystis jiroveciiand susceptibility assays suggest its sensitivity to caspofungin

Luraschi

Richard

Hauser

2018

Preprint

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“…Animals receiving this treatment could not transmit Pneumocystis to cohoused immunosuppressed Pneumocystis-free animals, while untreated infected animals were able to transmit infection, supporting the hypothesis of the cyst being the infectious form. This finding was further strengthened by a study using nude rats and cell-sorted P. carinii cyst and trophic forms (427). Rats infected with cysts alone were able to transmit the infection to receiver rats after 12 h of cohousing, while rats infected with trophic forms alone were not.…”

Section: Transmissionmentioning

confidence: 95%

A Molecular Window into the Biology and Epidemiology of Pneumocystis spp

2018

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, a unique atypical fungus with an elusive lifestyle, has had an important medical history. It came to prominence as an opportunistic pathogen that not only can cause life-threatening pneumonia in patients with HIV infection and other immunodeficiencies but also can colonize the lungs of healthy individuals from a very early age. The genus includes a group of closely related but heterogeneous organisms that have a worldwide distribution, have been detected in multiple mammalian species, are highly host species specific, inhabit the lungs almost exclusively, and have never convincingly been cultured, making a fascinating but difficult-to-study organism. Improved molecular biologic methodologies have opened a new window into the biology and epidemiology of. Advances include an improved taxonomic classification, identification of an extremely reduced genome and concomitant inability to metabolize and grow independent of the host lungs, insights into its transmission mode, recognition of its widespread colonization in both immunocompetent and immunodeficient hosts, and utilization of strain variation to study drug resistance, epidemiology, and outbreaks of infection among transplant patients. This review summarizes these advances and also identifies some major questions and challenges that need to be addressed to better understand biology and its relevance to clinical care.

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“…33 This complex technique has been 144 successfully applied to the recovery of P. carinii from lungs and BAL fluid of rats and 145 used to investigate life-cycle, but has limited use in routine diagnostics. [34][35][36] …”

mentioning

confidence: 99%