Biology subjects

Mulondo, R.

Publications and source records attributed to Mulondo, R..

4 recordsLinked to original sources

bioRxiv2026

The aging mouse lipidome

Aging is associated with widespread metabolic changes that contribute to functional decline and disease. While prior studies have characterized age-associated changes in lipids, it still remains incompletely understood how the lipidome changes across tissues and between sexes during aging. Here, we performed targeted lipidomics across 10 organs collected from male and female mice at five ages spanning adolescence to old age. We analyzed 775 lipids across multiple lipid classes and found that aging affects the lipidome in an organ-specific manner. The thymus and quadriceps muscle had the most age-associated lipid changes, whereas lipid levels in organs such as the kidney and lung remained more stable. In quadriceps muscle, aging was associated with a decrease in specific phosphatidylcholine and phosphatidylethanolamine lipids, particularly those containing adrenic acid. We also identified sex-dependent differences in lipid composition, with the spleen showing differences throughout life. Spleens from female mice had lower levels of lysophosphatidylcholine and lysophosphatidylethanolamine compared to males. Together, these data provide a comprehensive atlas of age- and sex-associated lipid changes across mouse organs and complement existing metabolic and transcriptomic resources to support studies of mouse aging.

molecular biology↗

bioRxiv2026

Whole genome sequencing-based characterization of mobile genetic elements in Staphylococcus aureus isolated from patients in Fort Portal Regional Referral Hospital, Western Uganda

BackgroundThe ability of Staphylococcus aureus to evolve through horizontal gene transfer mechanisms aids its success as a versatile pathogen. Mobile genetic elements (MGEs) are linked to potent virulence factors in S. aureus, e.g., the Panton-Valentine leukocidin and toxic shock syndrome toxins, as well as antibiotic resistance genes, e.g., mecA that encodes methicillin resistance. Despite their clinical relevance, molecular surveillance of MGEs in Africa remains limited. Here, we characterize the MGE repertoire of clinically relevant S. aureus isolates from Fort Portal Regional Referral Hospital (FPRRH), western Uganda. MethodsWe assembled a total of 40 genome sequences from previously sequenced S. aureus isolates cultured from patients (skin wounds, urinary tract, and bloodstream infections) at FPRRH during 2017-2019. spaTyper was used to determine the spa genotypes, while the presence of MGEs was screened and annotated for using PlasmidFinder, PHASTEST, Mobile Element Finder, SCCmecFinder, Bakta, MobileOG-db, and IslandViewer tools. ResultsEleven spa types were identified, with spa type t355 predominating. We detected 74 plasmid-derived sequences and 31 insertion sequences. Two SCCmec types, SCCmec type III and SCCmec type IV, were detected, indicating both hospital-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA). Forty-seven intact prophages (all Siphoviridae) were identified, carrying dfrG, sak, and lukPV genes. A total of 191 genomic islands were detected, and these harbored the virulence, immunoevasion, drug, and heavy metal resistance genes, such as nuc, tuf, tst, pvl, tet, blaZ, and mer genes. ConclusionsS. aureus at FPRRH harbors a diverse and functionally rich MGE repertoire, including genomic islands, prophages, insertion sequences, transposons, and plasmids, that contribute to the dissemination of virulence, AMR, and metal resistance determinants. The coexistence of HA-MRSA and CA-MRSA, as seen in other regions of Uganda, underscores the importance of continued genomic surveillance to inform infection control strategies.

genomics↗

bioRxiv2024

A metabolic atlas of mouse aging

Humans are living longer, but this is accompanied by an increased incidence of age-related chronic diseases. Many of these diseases are influenced by age-associated metabolic dysregulation, but how metabolism changes in multiple organs during aging in males and females is not known. Answering this could reveal new mechanisms of aging and age-targeted therapeutics. In this study, we describe how metabolism changes in 12 organs in male and female mice at 5 different ages. Organs show distinct patterns of metabolic aging that are affected by sex differently. Hydroxyproline shows the most consistent change across the dataset, decreasing with age in 11 out of 12 organs investigated. We also developed a metabolic aging clock that predicts biological age and identified alpha-ketoglutarate, previously shown to extend lifespan in mice, as a key predictor of age. Our results reveal fundamental insights into the aging process and identify new therapeutic targets to maintain organ health.

molecular biology↗

bioRxiv2020

Vaginal Microbiome Topic Modelling of Laboring Ugandan Women With and Without Fever

The composition of the maternal vaginal microbiome may influence the duration of pregnancy, onset of labor and even neonatal outcomes. Maternal microbiome research in sub Saharan-Africa has focused on non-pregnant and postpartum composition of the vaginal microbiome. We examined the vaginal microbiome composition of 99 laboring Ugandan women using routine microbiology and 16S ribosomal DNA sequencing from two hypervariable regions (V1-V2 and V3-V4), using standard hierarchical methods. We then introduce Grades of Membership (GoM) modeling for the vaginal microbiome, a method often used in the text mining machine learning literature. Leveraging GoM models, we create a basis composed of a small number of microbial topics whose linear combination optimally represents each patient yielding more accurate associations. We identified relationships between defined communities and the presentation or absence of intrapartum fever. Using a random forest model we showed that by including novel microbial topic models we improved upon clinical variables to predict maternal fever. We also show by integrating clinical variables with a microbial topic model into this model found young maternal age, fever report earlier in the current pregnancy, and longer labors, as well as a more diverse, less Lactobacillus dominated microbiome were features of labor associated with intrapartum fever. These results better define relationships between presentation or absence of intrapartum fever, demographics, peripartum course, and vaginal microbial communities, and improve our understanding of the impact of the microbiome on maternal and neonatal infection risk.

genomics↗