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Evolutionary Relationships Among Staphylococci and the Prevention of Staphylococcus aureus Nasal Colonization
Title
Evolutionary Relationships Among Staphylococci and the Prevention of Staphylococcus aureus Nasal Colonization.
Creator
Lamers, Ryan, Cole, Alexander, Parkinson, Christopher, Chai, Xinqing, Moore, Sean, University of Central Florida
Abstract / Description
Staphylococcus is a significant cause of human infection and mortality, worldwide. Currently, there are greater than 60 taxa within Staphylococcus, and nearly all are pathogenic. The collective potential for virulence among species of Staphylococcus heightens the overall clinical significance of this genus and argues for a thorough understanding of the evolutionary relationships among species. Within Staphylococcus, aureus is the most common cause of human infection, where nasal carriage of...
Show moreStaphylococcus is a significant cause of human infection and mortality, worldwide. Currently, there are greater than 60 taxa within Staphylococcus, and nearly all are pathogenic. The collective potential for virulence among species of Staphylococcus heightens the overall clinical significance of this genus and argues for a thorough understanding of the evolutionary relationships among species. Within Staphylococcus, aureus is the most common cause of human infection, where nasal carriage of this bacterium is a known risk factor for autoinfection. The predisposition to infection by nasal carriers of S. aureus, and the ease with which strains are transferred between individuals, suggests that nasal carriage is a major vector for the transmission of virulent strains throughout the community. This hypothesis, however, has not been assessed in any great detail to identify the genetic relationships between clinical isolates of S. aureus and those strains being carried asymptomatically throughout the community. Also lacking within this field is a unified and robust estimate of phylogeny among species of Staphylococcus.Here, we report on a highly unified species phylogeny for Staphylococcus that has been derived using multilocus nucleotide data under multiple Bayesian and maximum likelihood approaches. Our findings are in general agreement with previous reports of the staphylococcal phylogeny, although we identify multiple previously unreported relationships. Regardless of methodology, strong nodal support and high topological agreement was observed with only minor variations in results between methods. Based on our phylogenetic estimates, we propose that Staphylococcus species can be evolutionarily clustered into 15 groups, and six species groups. In addition, our more defined phylogenetic analyses of S. aureus revealed strong genetic associations between both nasal carriage strains and clinical isolates. Genetic analyses of hypervariable regions from virulence genes revealed that not only do clinically relevant strains belong to identical genetic lineages as the nasal carriage isolates, but they also exhibited 100% sequence similarity within these regions. Our findings indicate that strains of S. aureus being carried asymptomatically throughout the community via nasal colonization are genetically related to those responsible for high levels of infection and mortality.Due to nasal carriage of S. aureus being a risk factor for autoinfection, standardized preoperative decolonization has become a major consideration for the prevention of nosocomial infection. Toward this end, we have identified the macrocyclic ?-defensin analogue RC-101 as a promising anti-S. aureus agent for nasal decolonization. RC-101 exhibited bactericidal effects against S. aureus in both epithelium-free systems, and ex vivo models containing human airway epithelia. Importantly, RC-101 exhibited potent anti-S. aureus activities against all strains tested, including USA300. Moreover, RC-101 significantly reduced the adherence, survival, and proliferation of S. aureus on human airway epithelia without any noted cellular toxicity or the induction of a proinflammatory response. Collectively, our findings identify RC-101 as a potential preventative of S. aureus nasal colonization.
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Date Issued
2011
Identifier
CFE0004124, ucf:49092
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0004124
Homologous Pairing Through DNA Driven Harmonics - A Simulation Investigation
Title
Homologous Pairing Through DNA Driven Harmonics - A Simulation Investigation.
Creator
Calloway, Richard, Proctor, Michael, Kincaid, John, Jaganathan, Balasubramanian, Gerber, Matthew, Chai, Xinqing, University of Central Florida
Abstract / Description
The objective of this research is to determine if a better understanding of the (")molecule of life("), deoxyribonucleic acid or DNA can be obtained through Molecular Dynamics (MD) modeling and simulation (M(&)S) using contemporary MD M(&)S. It is difficult to overstate the significance of the DNA molecule. The now-completed Human Genome Project stands out as the most significant testimony yet to the importance of understanding DNA. The Human Genome Project (HGP) enumerated many areas of...
Show moreThe objective of this research is to determine if a better understanding of the (")molecule of life("), deoxyribonucleic acid or DNA can be obtained through Molecular Dynamics (MD) modeling and simulation (M(&)S) using contemporary MD M(&)S. It is difficult to overstate the significance of the DNA molecule. The now-completed Human Genome Project stands out as the most significant testimony yet to the importance of understanding DNA. The Human Genome Project (HGP) enumerated many areas of application of genomic research including molecular medicine, energy sources, environmental applications, agriculture and livestock breeding to name just a few. (Science, 2008) In addition to the fact that DNA contains the informational blueprints for all life, it also exhibits other remarkable characteristics most of which are either poorly understood or remain complete mysteries. One of those completely mysterious characteristics is the ability of DNA molecules to spontaneously segregate with other DNA molecules of similar sequence. This ability has been observed for years in living organisms and is known as (")homologous pairing.(") It is completely reproducible in a laboratory and defies explanation. What is the underlying mechanism that facilitates long-range attraction between 2 double-helix DNA molecules containing similar nucleotide sequences? The fact that we cannot answer this question indicates we are missing a fundamental piece of information concerning the DNA bio-molecule. The research proposed herein investigated using the Nano-scale Molecular Dynamics NAMD (Phillips et al., 2005) simulator the following hypotheses:H(Simulate Observed Closure NULL) : = Current MD force field models when used to model DNA molecule segments, contain sufficient variable terms and parameters to describe and reproduce directed segregating movement (closure of the segments) as previously observed by the Imperial College team between two Phi X 174 DNA molecules. H(Resonance NULL) : = Current MD force field models when used to model DNA molecule segments in a condensed phased solvent contain sufficient variable terms and parameters to reproduce theorized molecular resonation in the form of frequency content found in water between the segments. H(Harmonized Resonance NULL) : = Current MD force field models of DNA molecule segments in a condensed phase solvent produce theorized molecular resonation in the form of frequency content above and beyond the expected normal frequency levels found in water between the segments. H(Sequence Relationship NULL): = The specific frequencies and amplitudes of the harmonized resonance postulated in H(Harmonized Resonance NULL) are a direct function of DNA nucleotide sequence. H(Resonance Causes Closure NULL) : = Interacting harmonized resonation produces an aggregate force between the 2 macro-molecule segments resulting in simulation of the same directed motion and segment closure as observed by the Imperial College team between two Phi X 174 DNA molecules. After nearly six months of molecular dynamic simulation for H(Simulate Observed Closure NULL) and H(Resonance Causes Closure NULL) no evidence of closure between two similar sequenced DNA segments was found. There exist several contributing factors that potentially affected this result that are described in detail in the Results section. Simulations investigating H( Resonance NULL), H(Harmonized Resonance NULL) and the emergent hypothesis H(Sequence Relationship NULL) on the other hand, revealed a rich selection of periodic pressure variation occurring in the solvent between simulated DNA molecules. About 20% of the power in Fourier coefficients returned by Fast Fourier Transforms performed on the pressure data was characterized as statistically significant and was located in less than 2% of the coefficients by count. This unexpected result occurred consistently in 5 different system configurations with considerable system-to-system variation in both frequency and magnitude. After careful analysis given the extent of our experiments the data was found to be in support of H( Resonance NULL), and H(Harmonized Resonance NULL) . Regarding the emergent hypothesis H(Sequence Relationship NULL), further analysis was done on the aggregate data set looking for correlation between nucleotide sequence and frequency/magnitude. Some of the results may be related to sequence but were insufficient to prove it. Overall the conflicting results were inconclusive so the hypothesis was neither accepted nor rejected. Of particular interest to future researchers it was noted that the computational simulations performed herein were NOT able to reproduce what we know actually happens in a laboratory environment. DNA segregation known to occur in-vitro during the Imperial College investigation did not occur in our simulation. Until this discrepancy is resolved MM simulation should not as yet be considered a suitable tool for further investigation of Homologous Chromosome Pairing. In Chapter 5 specific follow on research is described in priority of need addressing several new questions.
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Date Issued
2011
Identifier
CFE0004472, ucf:49302
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0004472
Thermally annealled plasmonic nanostructures
Title
Thermally annealled plasmonic nanostructures.
Creator
Wang, Chaoming, Su, Ming, Coffey, Kevin, Chai, Xinqing, Schelling, Patrick, University of Central Florida
Abstract / Description
Localized surface plasmon resonance (LSPR) is induced in metal nanoparticles by resonance between incident photons and conduction electrons in nanoparticles. For noble metal nanoparticles, LSPR can lead to strong absorbance of ultraviolet-violet light. Although it is well known that LSPR depends on the size and shape of nanoparticles, the inter-particle spacing, the dielectric properties of metal and the surrounding medium, the temperature dependence of LSPR is not well understood. By...
Show moreLocalized surface plasmon resonance (LSPR) is induced in metal nanoparticles by resonance between incident photons and conduction electrons in nanoparticles. For noble metal nanoparticles, LSPR can lead to strong absorbance of ultraviolet-violet light. Although it is well known that LSPR depends on the size and shape of nanoparticles, the inter-particle spacing, the dielectric properties of metal and the surrounding medium, the temperature dependence of LSPR is not well understood. By thermally annealing gold nanoparticle arrays formed by nanosphere lithography, a shift of LSPR peak upon heating has been shown. The thermal characteristics of the plasmonic nanoparticles have been further used to detect chemicals such as explosive and mercury vapors, which allow direct visual observation of the presence of mercury vapor, as well as thermal desorption measurements.
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Date Issued
2012
Identifier
CFE0004454, ucf:49322
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0004454