Sucrose-dependent accumulation of oral streptococci and their adhesion-defective mutants on saliva-coated hydroxyapatite

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73122/1/j.1399-302X.1995.tb00139.x.pd

Comparing the impact of increasing condom use or HIV pre-exposure prophylaxis (PrEP) use among female sex workers.

In many settings, interventions targeting female sex workers (FSWs) could significantly reduce the overall transmission of HIV. To understand the role HIV pre-exposure prophylaxis (PrEP) could play in controlling HIV transmission amongst FSWs, it is important to understand how its impact compares with scaling-up condom use-one of the proven HIV prevention strategies for FSWs. It is important to remember that condoms also have other benefits such as reducing the incidence of sexually transmitted infections and preventing pregnancy. A dynamic deterministic model of HIV transmission amongst FSWs, their clients and other male partners (termed 'pimps') was used to compare the protection provided by PrEP for HIV-negative FSWs with FSWs increasing their condom use with clients and/or pimps. For different HIV prevalence scenarios, levels of pimp interaction, and baseline condom use, we estimated the coverage of PrEP that gives the same reduction in endemic FSW HIV prevalence or HIV infections averted as different increases in condom use. To achieve the same impact on FSW HIV prevalence as increasing condom use by 1%, the coverage of PrEP has to increase by >2%. The relative impact of PrEP increases for scenarios where pimps contribute to HIV transmission, but not greatly, and decreases with higher baseline condom use. In terms of HIV infections averted over 10 years, the relative impact of PrEP compared to condoms was reduced, with a >3% increase in PrEP coverage achieving the same impact as a 1% increase in condom use. Condom promotion interventions should remain the mainstay HIV prevention strategy for FSWs, with PrEP only being implemented once condom interventions have been maximised or to fill prevention gaps where condoms cannot be used

A Bayesian approach to estimate changes in condom use from limited human immunodeficiency virus prevalence data.

Evaluation of large-scale intervention programmes against human immunodeficiency virus (HIV) is becoming increasingly important, but impact estimates frequently hinge on knowledge of changes in behaviour such as the frequency of condom use over time, or other self-reported behaviour changes, for which we generally have limited or potentially biased data. We employ a Bayesian inference methodology that incorporates an HIV transmission dynamics model to estimate condom use time trends from HIV prevalence data. Estimation is implemented via particle Markov chain Monte Carlo methods, applied for the first time in this context. The preliminary choice of the formulation for the time varying parameter reflecting the proportion of condom use is critical in the context studied, because of the very limited amount of condom use and HIV data available. We consider various novel formulations to explore the trajectory of condom use over time, based on diffusion-driven trajectories and smooth sigmoid curves. Numerical simulations indicate that informative results can be obtained regarding the amplitude of the increase in condom use during an intervention, with good levels of sensitivity and specificity performance in effectively detecting changes. The application of this method to a real life problem demonstrates how it can help in evaluating HIV interventions based on a small number of prevalence estimates, and it opens the way to similar applications in different contexts

Transcriptome analysis of <i>Streptococcus gordonii </i>Challis DL1 indicates a role for the biofilm-associated <i>fruRBA </i>operon in response to <i>Candida albicans</i>

Multiple levels of interkingdom signaling have been implicated in maintaining the ecological balance between Candida albicans and commensal streptococci to assure a state of oral health. To better understand the molecular mechanisms involved in the initial streptococcal response to the presence of C. albicans that can initiate oral surface colonization and biofilm formation, hypha-forming cells were incubated with Streptococcus gordonii cells for 30 minutes to assess the streptococcal transcriptome response. A genome wide microarray analysis and quantitative PCR validation of S. gordonii transcripts identified a number of genes, the majority of which were involved in metabolic functions that were differentially expressed in the presence of hyphae. The fruR, fruB and fruA genes encoding the transcriptional regulator, fructose-1-phosphate kinase, and fructose-specific permease, respectively, of the phosphoenolpyruvate-dependent fructose phosphotransferase system, were consistently up-regulated. An S. gordonii mutant in which these genes were deleted by allelic replacement, formed an architecturally-distinct, less robust biofilm with C. albicans than did parental strain cells. Complementing the mutant with plasmid borne fruR, fruB and fruA genes caused phenotype reversion, indicating that the genes in this operon played a role in dual species biofilm formation. This genome wide analysis of the S. gordonii transcriptional response to C. albicans has identified several genes that have potential roles in interkingdom signaling and responses

Interaction of Salivary alpha-Amylase and Amylase-Binding-Protein A (AbpA) of Streptococcus gordonii with Glucosyltransferase of S. gordonii and Streptococcus mutans

<p>Abstract</p> <p>Background</p> <p>Glucosyltransferases (Gtfs), enzymes that produce extracellular glucans from dietary sucrose, contribute to dental plaque formation by <it>Streptococcus gordonii </it>and <it>Streptococcus mutans</it>. The alpha-amylase-binding protein A (AbpA) of <it>S. gordonii</it>, an early colonizing bacterium in dental plaque, interacts with salivary amylase and may influence dental plaque formation by this organism. We examined the interaction of amylase and recombinant AbpA (rAbpA), together with Gtfs of <it>S. gordonii </it>and <it>S. mutans</it>.</p> <p>Results</p> <p>The addition of salivary alpha-amylase to culture supernatants of <it>S. gordonii </it>precipitated a protein complex containing amylase, AbpA, amylase-binding protein B (AbpB), and the glucosyltransferase produced by <it>S. gordonii </it>(Gtf-G). rAbpA was expressed from an inducible plasmid, purified from <it>Escherichia coli </it>and characterized. Purified rAbpA, along with purified amylase, interacted with and precipitated Gtfs from culture supernatants of both <it>S. gordonii </it>and <it>S. mutans</it>. The presence of amylase and/or rAbpA increased both the sucrase and transferase component activities of <it>S. mutans </it>Gtf-B. Enzyme-linked immunosorbent assay (ELISA) using anti-Gtf-B antibody verified the interaction of rAbpA and amylase with Gtf-B. A <it>S. gordonii abp</it>A-deficient mutant showed greater biofilm growth under static conditions than wild-type in the presence of sucrose. Interestingly, biofilm formation by every strain was inhibited in the presence of saliva.</p> <p>Conclusion</p> <p>The results suggest that an extracellular protein network of AbpA-amylase-Gtf may influence the ecology of oral biofilms, likely during initial phases of colonization.</p

Compartmentalized cAMP Generation by Engineered Photoactivated Adenylyl Cyclases

Because small-molecule activators of adenylyl cyclases (AC) affect ACs cell-wide, it is challenging to explore the signaling consequences of AC activity emanating from specific intracellular compartments. We explored this issue using a series of engineered, optogenetic, spatially restricted, photoactivable adenylyl cyclases (PACs) positioned at the plasma membrane (PM), the outer mitochondrial membrane (OMM), and the nucleus (Nu). The biochemical consequences of brief photostimulation of PAC is primarily limited to the intracellular site occupied by the PAC. By contrast, sustained photostimulation results in distal cAMP signaling. Prolonged cAMP generation at the OMM profoundly stimulates nuclear protein kinase (PKA) activity. We have found that phosphodiesterases 3 (OMM and PM) and 4 (PM) modulate proximal (local) cAMP-triggered activity, whereas phosphodiesterase 4 regulates distal cAMP activity as well as the migration of PKA's catalytic subunit into the nucleus