Biology subjects

Katabazi, F. A.

Publications and source records attributed to Katabazi, F. A..

2 recordsLinked to original sources

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↗

bioRxiv2025

Patterns of compensatory mutations in rpoA/B/C genes of multidrug resistant M. tuberculosis in Uganda

Mutations in rpoB, a gene that encodes the bacterial RNA polymerase (RNAP) beta-subunit, can cause high-level resistance to rifampicin. Approximately 95% of rifampicin-resistant Mycobacterium tuberculosis clinical isolates possess mutations in an 81-base pair rpoB region referred to as the rifampicin-resistance determining region (rpoB/RRDR). Also, rifampicin-resistant M. tuberculosis clinical isolates carry multiple mutations in RNAP genes (i.e., rpoA, rpoB, rpoC, rpoD), particularly rpoA and rpoC, which encode the alpha-(2) and beta'-({beta}') subunits, respectively. Such secondary mutations offset the fitness cost associated with rifampicin-resistance mutations in M. tuberculosis, resulting in resistant strains that are as fit as the wildtype drug-susceptible strains. To analyse the patterns of compensatory mutations in RNAP encoding genes of rifampicin-resistant M. tuberculosis clinical isolates in Uganda, whole genome sequencing and Sanger DNA sequencing were performed on 52 M. tuberculosis clinical isolates - 20 drug-susceptible and 32 multidrug resistant (MDR). A total of 24 (75%) MDR-TB isolates had high-level rifampicin-resistance conferring mutations in rpoB/RRDR i.e., Ser531Leu (31%); His526Asp (6%); His526Leu (3%); His526Tyr (3%); His526Arg (3%); His526Gly (3%); Asp516Tyr (13%); Asp516Val (6%); Glu513Lys (3%); Leu511Pro (3%); Leu492Leu (3%); Gln490Arg (3%). Further, two putative compensatory mutations (Gln490Arg & Lys1025Glu) outside the RRDR and not resistance conferring were found in rpoB. Altogether, 16 (50%) MDR-TB isolates with rpoB/RRDR resistance conferring mutations had non-synonymous mutations in rpoC of the following patterns Leu39Phe (3%); Tyr61His (3%); Asp271Gly (3%); Ser377Ala (3%); Pro481Thr (3%); Val483Ala (6%); Leu516Pro (3%); Ala521Asp (3%); Gly594Glu (13%); Asn698Ser (3%); Leu823Pro (3%). In conclusion, putative compensatory mutations are prevalent in rifampicin-resistant M. tuberculosis clinical isolates in Uganda, with rpoC/Gly594Glu and rpoC/Val483Ala as the most frequent. Further studies will determine their association with strain genetic background, fitness and transmission in an endemic setting with a high burden of HIV-TB coinfection.

microbiology↗