Project description:The main purpose of this article is to formulate a deterministic mathematical model for the transmission of malaria that considers two host types in the human population. The first type is called "non-immune" comprising all humans who have never acquired immunity against malaria and the second type is called "semi-immune". Non-immune are divided into susceptible, exposed and infectious and semi-immune are divided into susceptible, exposed, infectious and immune. We obtain an explicit formula for the reproductive number, R(0) which is a function of the weight of the transmission semi-immune-mosquito-semi-immune, R(0a), and the weight of the transmission non-immune-mosquito-non-immune, R(0e). Then, we study the existence of endemic equilibria by using bifurcation analysis. We give a simple criterion when R(0) crosses one for forward and backward bifurcation. We explore the possibility of a control for malaria through a specific sub-group such as non-immune or semi-immune or mosquitoes
Project description:Our group recently transcriptomically characterized coculture growth between Streptococcus mutans and several species of commensal streptococci (Rose et al, 2023). However, these experiments were carried out in our lab-based experimental medium, tryptone and yeast extract (TY-). To understand whether culturing these species within a medium that more closely mimics their natural environment alters the interaction, we evaluated both monoculture and coculture growth between the dental caries pathogen Streptococcus mutans and oral commensal species Streptococcus oralis in a half TY- / half human saliva mix that was optimally chosen based on our initial characterization of oral streptococci behaviors in medium mixes containing saliva. Our results surprising show that inclusion of saliva enhances the competition of Streptococcus mutans against commensal streptococci through upregulation of carbohydrate uptake and glycolytic pathways.
Project description:Bacteria spatially confine cellular processes like protease secretion and signal transduction in membrane platforms termed functional membrane microdomains, which in certain organisational and functional features resemble the lipid rafts of eukaryotic cells. However, a rigorous understanding of their composition, assembly and biological significance is unknown. Here we use the human pathogen methicillin-resistant Staphylococcus aureus (MRSA) to show that the organization of these platforms requires a preferential interaction between unphosphorylated membrane saccharolipids and the scaffold protein flotillin. This interaction leads to their accumulation in specific membrane microdomains concomitantly to the attraction of membrane-associated multimeric complexes, for which flotillin promotes efficient oligomerization. One of these harbored proteins is the penicillin-binding protein PBP2a, responsible for penicillin resistance in MRSA. We took PBP2a as showcase to demonstrate that flotillin mutants are also defective in PBP2a oligomerization and activity. Thus, perturbation of microdomains assembly, using commercially available drugs, interferes with PBP2a oligomerization and causes a relapse of MRSA penicillin resistance in vitro and in vivo, resulting in MRSA infections susceptible to conventional penicillin treatments. Our study shows that bacterial cells organize sophisticated programs for cellular compartmentalization and unravels a novel strategy to develop antimicrobial therapies for multi-drug resistance pathogens.
Project description:In microbial production of non-catabolic products, a loss of production capacity upon long-term cultivation (for example, chemostat), a phenomenon called strain degeneration, is nearly always observed. In this study, a systems biology approach (monitoring changes from gene to produced flux) was used to study degeneration of penicillin production by Penicillium chrysogenum in ethanol-limited chemostat fermentations where the biomass specific penicillin production rate decreased 10-fold within 30 generations. Results showed that the copy number of penicillin gene clusters and expression levels of central metabolism showed little decrease. With respect to penicillin production, major changes were observed: a strong downregulation of the cysteine pathway in agreement with its nearly 10-fold flux reduction. Also, levels of ACVS and IPNS, two penicillin pathway enzymes, and the penicillin transport capacity decreased many fold. This indicates that degeneration is caused by changed regulation of post-translational modifications or an increased protein degradation rate of these proteins. Continued subcultivation of a degenerated culture resulted in partial recovery of the biomass specific penicillin production rate, however, it was still 5-fold lower than the peak biomass specific penicillin production rate.
2011-06-10 | GSE24212 | GEO
Project description:Whole Genome Sequencing of Group A Streptococci
| PRJNA559889 | ENA
Project description:Whole genome sequences of Group B Streptococci
Project description:Lcn972 is a non-modified bacteriocin that targets exclusively Lactococcus sp. Addition of Lcn972 inhibits cell wall biosynthesis at the septum by binding to the cell wall precursor lipid II. Resistance to Lcn972 develops upon selection with subinhibitory concentrations. The transcriptome of the highly resistant L. lactis D1 derived from the susceptible strain L. lactis MG1614 was compared. Fourteen genes were significantly up-regulated and 29 were down-regulated (expression change > 2-fold, p<0.001). Down-regulation was mostly found in sugar catabolic genes. Up-regulated genes included members of the cell envelope stress (CesR) regulon, the penicillin-binding protein pbpX and llmg2447, which may encode a putative extracytoplasmic function (ECF) anti-sigma factor located downstream of a non-functional ECF-sigX. Up-regulation of llmg2447 was linked to integration of IS981 that exchanged the -35 promoter region of llmg2447. Over-expression of llmg2447 resulted in highly Lcn972-resistant L. lactis transformants. The transcriptomes of Lactococcus lactis MG1614 susceptible to Lcn972 and L. lactis D1 resistant to Lcn972, grown under laboratory conditions, were compared using four biological replicates.