Biology subjects

Babalola, C. P.

Publications and source records attributed to Babalola, C. P..

4 recordsLinked to original sources

bioRxiv2026

Identification of Antibiofilm Agents against Salmonella enterica from the Pathogen Box Compound Library

BackgroundBiofilms are central to Salmonella pathogenesis, and targeting their formation is believed to produce less evolutionary pressure of growth inhibition than traditional antibacterials. In this study, we screened the Medicines for Malaria Venture (MMV) Pathogen Box library to identify anti-biofilm agents against S. enterica that possess drug-like properties. Methodology/ Principal FindingsA crystal-violet-based medium-throughput antibiofilm screen of Salmonella enterica serovar Typhimurium ATCC 14028 and a clinical Salmonella enterica serovar Elisabethville isolate was performed on polystyrene surfaces using the 400-compound Pathogen Box library. Compounds that inhibited biofilm formation by >30% and growth by <10% were identified as hits. Salmonella red-dry-rough and motility phenotypes were explored in mechanism of action studies on one hit compound. The Salmonella antibiofilm hit rate was 0.75% for this library. MMV688371 (benzamide) inhibited biofilm formation of S. Typhimurium ATCC 14028 by 33% without inhibiting growth. An ethambutol analogue (MMV687273) and auranofin (MMV688978) met the hit criteria against S. Elisabethville LLD035X. Auranofin showed concentration-dependent, growth-inhibition-independent antibiofilm activity against typhoidal and non-typhoidal Salmonella from Nigeria, and inhibited the motility of S. Elisabethville LLD035X at 5 {micro}M. At 5 {micro}M aurothioglucose, an auranofin gold (I) analogue, and non-gold analogue 1-Thio-beta-D-glucose tetraacetate, inhibited biofilm formation by 61.30% and 11.39%, respectively, pointing to essentiality of the gold (I) moiety for activity. Conclusions/ SignificanceStructurally diverse small molecules can inhibit biofilm formation by Salmonella, and motility inhibition is an important mechanism for this activity. Auranofin inhibits typhoidal and non-typhoidal Salmonella biofilm formation, with its gold content being required for these activities.

microbiology↗

bioRxiv2021

Antibiofilm agents with therapeutic potential against enteroaggregative Escherichia coli

BackgroundEnteroaggregative Escherichia coli (EAEC) is a predominant but neglected enteric pathogen implicated in infantile diarrhoea and nutrient malabsorption. There are no non-antibiotic approaches to dealing with persistent infection by these exceptional colonizers, which form copious biofilms. We screened the Medicines for Malaria Venture Pathogen Box for chemical entities that inhibit EAEC biofilm formation. MethodologyWe used two EAEC strains, 042 and MND005E, in a medium-throughput crystal violet-based antibiofilm screen. Hits were confirmed in concentration-dependence, growth kinetic and time course assays and activity spectra were determined against a panel of genome-sequenced EAEC. Antibiofilm activity against isogenic EAEC mutants, molecular docking simulations and comparative genomic analysis were used to identify the mechanism of action of one hit. Principal findingsIn all, five compounds (1.25%) reproducibly inhibited biofilm accumulation by at least one strain by 30-85% while inhibiting growth by under 10%. Hits exhibited at least 10-fold greater antibiofilm activity than nitazoxanide, the only known EAEC biofilm inhibitor. Reflective of known EAEC heterogeneity, only one hit was active against both screen isolates, but three hits showed broad antibiofilm activity against a larger panel of strains. Mechanism of action studies point to the EAEC anti-aggregation protein (Aap), dispersin, as the target of compound MMV687800. ConclusionsThis study identified five compounds not previously described as anti-adhesins or Gram-negative antibacterials with significant and specific EAEC antibiofilm activity. One molecule, MMV687800, targets the EAEC Aap. In vitro small-molecule inhibition of EAEC colonization opens a way to new therapeutic approaches to preventing and treating EAEC infection. Author summaryDiarrhoea accounts for over half a million deaths in children under five annually. It additionally contributes to childhood malnutrition as well as growth and development deficiencies, particularly in low-income countries. Enteroaggregative Escherichia coli (EAEC) causes diarrhoea that is often persistent and can also contribute to growth deficiencies in young children. EAEC is a neglected pathogen that is often resistant to antimicrobial drugs. Small molecules that block EAEC colonization may hold the key to interfering with EAEC disease without promoting antimicrobial resistance. We screened the Medicines for Malaria Ventures Pathogen Box for chemicals that can interfere with EAEC biofilm formation, a key colonization indicator. Our screen identified five biofilm-inhibiting molecules that did not interfere with bacterial viability and therefore are unlikely to exert strong pressure for resistance. Molecular biology and computational investigations point to the EAEC anti-aggregative protein, also known as dispersin, as a possible target for one of these hit molecules. Optimizing EAEC antibiofilm hits will create templates that can be employed for resolving EAEC diarrhoea and related infections.

microbiology↗

bioRxiv2021

Hoslundia opposita and other Nigerian plants inhibit sickle hemoglobin polymerization and prevent erythrocyte sickling: a virtual screening-guided identification of bioactive plants.

In sickle cell disease, a hereditary hemoglobinopathy, clinically observed disease presentations are the endpoint of a point mutation involving the substitution of glutamic acid with valine at the position 6 of the beta globin chain. With about 4.4 million people globally being affected, and another 43 million people bearing the sickle cell trait, several research efforts have been made to discover new and affordable treatment and possibly cure for the disease. Africa is endowed with a large flora population and traditional healers and citizens have over time depended on the use of herbs in folkloric medicine for different ailments including sickle cell disease (SCD). Such native knowledge has often formed the basis for different research exploration into the anti-sickling activities of selected African plants. These plants that have been so far investigated for their anti-sickling properties represent about 0.05 % of the 45,000 plant species enriching the flora landscape in Sub-Saharan Africa. Some of these have yielded potent anti-sickling profiles. In the current work we seek to achieve a more extensive search of the African plant diversity with anti-sickling properties: for this we have adopted a hybrid computational-cum-experimental protocol that employed computer-aided drug design (CADD) means for identifying plants with at least one constituent capable of interacting with the sickle hemoglobin, followed by extractive procedures and anti-sickling experiments for validating the predictions. Over two thousand (or 2,000) African natural products, representing over 200 plant species, were first virtually screened against the crystal structure of the dimerized human sickle hemoglobin. The natural products with the best computed sickle hemoglobin interaction energetics were found to belong to five plant species including Catharanthus roseus, Rauvolfia vomitoria, Hoslundia opposita, Lantana camara and Euphorbia hirta. The leaves of these plants were each collected subsequently and subjected to standard processing and extraction procedures. Using both HbSS polymerization inhibition and sickling reversal tests significant reductions in polymerization of erythrocyte hemolysate of the HbSS genotype were observed with the methanolic extracts of the plants, as well as sickling reversal levels of up to 68.50 % (H. opposita) was observed.

bioinformatics↗

bioRxiv2020

Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes

Black women of African ancestry experience more aggressive breast cancer with higher mortality rates than White women of European ancestry. Although inter-ethnic germline variation is known, differential somatic evolution has not been investigated in detail. Analysis of deep whole genomes of 97 breast tumors, with RNA-seq in a subset, from indigenous African patients in Nigeria in comparison to The Cancer Genome Atlas (n=76) revealed a higher rate of genomic instability and increased intra-tumoral heterogeneity as well as a unique genomic subtype defined by early clonal GATA3 mutations and a 10.5-year younger age at diagnosis. We also found evidence for non-coding mutations in two novel drivers (ZNF217 and SYPL1) and a novel INDEL signature strongly associated with African ancestry proportion. This comprehensive analysis of an understudied population underscores the need to incorporate diversity of genomes as a key parameter in fundamental research with potential to tailor clinical intervention and promote equity in precision oncology care.

genomics↗