Investigating metabolic and molecular ecological evolution of opportunistic pulmonary fungal coinfections: protocol for a laboratory-based cross-sectional study

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dc.contributor.authorNjovu, Israel Kiiza
dc.contributor.authorNalumaga, Pauline Petra
dc.contributor.authorAmpaire, Lucas
dc.contributor.authorNuwagira, Edwin
dc.contributor.authorMwesigye, James
dc.contributor.authorMusinguzi, Benson
dc.contributor.authorKassaza, Kennedy
dc.contributor.authorTaseera, Kabanda
dc.contributor.authorMukasa, James Kiguli
dc.contributor.authorBazira, Joel
dc.contributor.authorIramiot, Jacob Stanley
dc.contributor.authorBaguma, Andrew
dc.contributor.authorBongomin, Felix
dc.contributor.authorKwizera, Richard
dc.contributor.authorAchan, Beatrice
dc.contributor.authorCox, Michael J
dc.contributor.authorKing, Jason S
dc.contributor.authorMay, Robin
dc.contributor.authorBallou, Elizabeth R
dc.contributor.authorItabangi, Herbert
dc.date.accessioned2023-10-06T16:25:01Z
dc.date.available2023-10-06T16:25:01Z
dc.date.issued2023-04-09
dc.description.abstractBackground: Fungal-bacterial cocolonization and coinfections pose an emerging challenge among patients suspected of having pulmonary tuberculosis (PTB); however, the underlying pathogenic mechanisms and microbiome interactions are poorly understood. Understanding how environmental microbes, such as fungi and bacteria, coevolve and develop traits to evade host immune responses and resist treatment is critical to controlling opportunistic pulmonary fungal coinfections. In this project, we propose to study the coexistence of fungal and bacterial microbial communities during chronic pulmonary diseases, with a keen interest in underpinning fungal etiological evolution and the predominating interactions that may exist between fungi and bacteria. Objective: This is a protocol for a study aimed at investigating the metabolic and molecular ecological evolution of opportunistic pulmonary fungal coinfections through determining and characterizing the burden, etiological profiles, microbial communities, and interactions established between fungi and bacteria as implicated among patients with presumptive PTB. Methods: This will be a laboratory-based cross-sectional study, with a sample size of 406 participants. From each participant, 2 sputa samples (one on-spot and one early morning) will be collected. These samples will then be analyzed for both fungal and bacterial etiology using conventional metabolic and molecular (intergenic transcribed spacer and 16S ribosomal DNA–based polymerase chain reaction) approaches. We will also attempt to design a genome-scale metabolic model for pulmonary microbial communities to analyze the composition of the entire microbiome (ie, fungi and bacteria) and investigate host-microbial interactions under different patient conditions. This analysis will be based on the interplays of genes (identified by metagenomics) and inferred from amplicon data and metabolites (identified by metabolomics) by analyzing the full data set and using specific computational tools. We will also collect baseline data, including demographic and clinical history, using a patient-reported questionnaire. Altogether, this approach will contribute to a diagnostic-based observational study. The primary outcome will be the overall fungal and bacterial diagnostic profile of the study participants. Other diagnostic factors associated with the etiological profile, such as incidence and prevalence, will also be analyzed using univariate and multivariate schemes. Odds ratios with 95% CIs will be presented with a statistical significance set at P<.05. Results: The study has been approved by the Mbarara University Research Ethic Committee (MUREC1/7-07/09/20) and the Uganda National Council of Science and Technology (HS1233ES). Following careful scrutiny, the protocol was designed to enable patient enrollment, which began in March 2022 at Mbarara University Teaching Hospital. Data collection is ongoing and is expected to be completed by August 2023, and manuscripts will be submitted for publication thereafter. Conclusions: Through this protocol, we will explore the metabolic and molecular ecological evolution of opportunistic pulmonary fungal coinfections among patients with presumptive PTB. Establishing key fungal-bacterial cross-kingdom synergistic relationships is crucial for instituting fungal bacterial coinfecting etiology.en_US
dc.description.sponsorshipEuropean Developing Countries Clinical Trials Partnership (EDCTP) in collaboration with the European Union (grant TMA 2019CDF-2789)en_US
dc.identifier.citationNjovu, I. K., Nalumaga, P. P., Ampaire, L., Nuwagira, E., Mwesigye, J., Musinguzi, B., ... & Itabangi, H. (2023). Investigating metabolic and molecular ecological evolution of opportunistic pulmonary fungal coinfections: protocol for a laboratory-based cross-sectional study. JMIR Research Protocols, 12(1), e48014.en_US
dc.identifier.issn1929-0748
dc.identifier.urihttps://dir.muni.ac.ug/handle/20.500.12260/566
dc.language.isoenen_US
dc.publisherJMIR Publicationsen_US
dc.subjectpulmonary mycosesen_US
dc.subjectfungal-bacterial coinfectionen_US
dc.subjectmetabolicen_US
dc.subjectevolutionaryen_US
dc.subjectopportunistic infectionsen_US
dc.subjectcross-kingdom interactionen_US
dc.subjecttuberculosisen_US
dc.titleInvestigating metabolic and molecular ecological evolution of opportunistic pulmonary fungal coinfections: protocol for a laboratory-based cross-sectional studyen_US
dc.typeArticleen_US

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