• Inhibiting N-acyl-homoserine lactone synthesis and quenching Pseudomonas quinolone quorum sensing to attenuate virulence

      Chan, K.; Liu, Y.; Chang, Chien-Yi (2015-10)
      Bacteria sense their own population size, tune the expression of responding genes, and behave accordingly to environmental stimuli by secreting signaling molecules. This phenomenon is termed as quorum sensing (QS). By exogenously manipulating the signal transduction bacterial population behaviors could be controlled, which may be done through quorum quenching (QQ). QS related regulatory networks have been proven their involvement in regulating many virulence determinants in pathogenic bacteria in the course of infections. Interfering with QS signaling system could be a novel strategy against bacterial infections and therefore requires more understanding of their fundamental mechanisms. Here we review the development of studies specifically on the inhibition of production of N-acyl-homoserine lactone (AHL), a common proteobacterial QS signal. The opportunistic pathogen, Pseudomonas aeruginosa, equips the alkylquinolone (AQ)-mediated QS which also plays crucial roles in its pathogenicity. The studies in QQ targeting on AQ are also discussed.
    • Modulation of host biology by Pseudomonas aeruginosa quorum sensing signal molecules: messengers or traitors

      Liu, Y.; Chan, K.; Chang, Chien-Yi (2015-11)
      Bacterial cells sense their population density and respond accordingly by producing various signal molecules to the surrounding environments thereby trigger a plethora of gene expression. This regulatory pathway is termed quorum sensing (QS). Plenty of bacterial virulence factors are controlled by QS or QS-mediated regulatory systems and QS signal molecules (QSSMs) play crucial roles in bacterial signaling transduction. Moreover, bacterial QSSMs were shown to interfere with host cell signaling and modulate host immune responses. QSSMs not only regulate the expression of bacterial virulence factors but themselves act in the modulation of host biology that can be potential therapeutic targets.
    • Optical control of nanoparticle catalysis influenced by photoswitch positioning in hybrid peptide capping ligands

      Lawrence, R.L.; Hughes, Zak E.; Cendan, V.J.; Liu, Y.; Lim, C.K.; Prasad, P.N.; Swihart, M.T.; Walsh, T.R.; Knecht, M.R. (2018-10)
      Here we present an in-depth analysis of structural factors that modulate peptide-capped nanoparticle catalytic activity via optically driven structural reconfiguration of the biointerface present at the particle surface. Six different sets of peptide-capped Au nanoparticles were prepared, in which an azobenzene photoswitch was incorporated into one of two well-studied peptide sequences with known affinity for Au, each at one of three different positions: The N- or C-terminus, or mid-sequence. Changes in the photoswitch isomerization state induce a reversible structural change in the surface-bound peptide, which modulates the catalytic activity of the material. This control of reactivity is attributed to changes in the amount of accessible metallic surface area available to drive the reaction. This research specifically focuses on the effect of the peptide sequence and photoswitch position in the biomolecule, from which potential target systems for on/off reactivity have been identified. Additionally, trends associated with photoswitch position for a peptide sequence (Pd4) have been identified. Integrating the azobenzene at the N-terminus or central region results in nanocatalysts with greater reactivity in the trans and cis conformations, respectively; however, positioning the photoswitch at the C-terminus gives rise to a unique system that is reactive in the trans conformation and partially deactivated in the cis conformation. These results provide a fundamental basis for new directions in nanoparticle catalyst development to control activity in real time, which could have significant implications in the design of catalysts for multistep reactions using a single catalyst. Additionally, such a fine level of interfacial structural control could prove to be important for applications beyond catalysis, including biosensing, photonics, and energy technologies that are highly dependent on particle surface structures.
    • Peptide-mediated growth and dispersion of Au nanoparticles in water via sequence engineering

      Nguyen, M.A.; Hughes, Zak E.; Liu, Y.; Li, Y.; Swihart, M.T.; Knecht, M.R.; Walsh, T.R. (2018-05)
      The use of peptides to nucleate, grow, and stabilize nanoparticles in aqueous media via non-covalent interactions offers new possibilities for creating functional, water-dispersed inorganic/organic hybrid materials, particularly for Au nanoparticles. Numerous previous studies have identified peptide sequences that both possess a strong binding affinity for Au surfaces and are capable of supporting nanoparticle growth in water. However, recent studies have shown that not all such peptide sequences can produce stable dispersions of these nanoparticles. Here, via integrated experiments and molecular modeling, we provide new insights into the many factors that influence Au nanoparticle growth and stabilization in aqueous media. We define colloidal stability by the absence of visible precipitation after at least 24 hours post-synthesis. We use binding affinity measurements, nanoparticle synthesis, characterization and stabilization assays, and molecular modeling, to investigate a set of sequences based on two known peptides with strong affinity for Au. This set of biomolecules is designed to probe specific sequence and context effects using both point mutations and global reorganization of the peptides. Our data confirm, for a broader range of sequences, that Au nanoparticle/peptide binding affinity alone is not predictive of peptide-mediated colloidal stability. By comparing nanoparticle stabilization assay outcomes with molecular simulations, we establish a correlation between the colloidal stability of the Au nanoparticles and the degree of conformational diversity in the surface-adsorbed peptides. Our findings suggest future routes to engineer peptide sequences for bio-based growth and dispersion of functional nanoparticles in aqueous media.