title: Lipopolysaccharide neutralizing peptide-porphyrin conjugates for effective photoinactivation and intracellular imaging of gram-negative bacteria strains.
abstract: A simple and specific strategy based on the bioconjugation of a photosensitizer protophophyrin IX (PpIX) with a lipopolysaccharide (LPS) binding antimicrobial peptide YI13WF (YVLWKRKRKFCFI-Amide) has been developed for the effective fluorescent imaging and photodynamic inactivation of Gram-negative bacterial strains. The intracellular fluorescent imaging and photodynamic antimicrobial chemotherapy (PACT) studies supported our hypothesis that the PpIX-YI13WF conjugates could serve as efficient probes to image the bacterial strains and meanwhile indicated the potent activities against Gram-negative bacterial pathogens especially for those with antibiotics resistance when exposed to the white light irradiation. Compared to the monomeric PpIX-YI13WF conjugate, the dimeric conjugate indicated the stronger fluorescent imaging signals and higher photoinactivation toward the Gram-negative bacterial pathogens throughout the whole concentration range. In addition, the photodynamic bacterial inactivation also demonstrated more potent activity than the minimum inhibitory concentration (MIC) values of dimeric PpIX-YI13WF conjugate itself observed for E. coli DH5a (~4 times), S. enterica (~8 times), and other Gram-negative strains including antibiotic-resistant E. coli BL21 (~8 times) and K. pneumoniae (~16 times). Moreover, both fluorescent imaging and photoinactivation measurements also demonstrated that the dimeric PpIX-YI13WF conjugate could selectively recognize bacterial strains over mammalian cells and generate less photo damage to mammalian cells. We believed that the enhanced fluorescence and bacterial inactivation were probably attributed to the higher binding affinity between dimeric photosensitizer peptide conjugate and LPS components on the surface of bacterial strains, which were the results of efficient multivalent interactions.
authors: Division of Chemistry & Biological Chemistry, School of Physical & Mathematical Sciences, Nanyang Technological University, Singapore 637371.
authors: Fang
authors: F
authors: Liu
authors: Annie
authors: A
authors: Soh Yan Ni
authors: Yingjie
authors: Y
authors: Lim
authors: Harini
authors: H
authors: Mohanram
authors: S
authors: S
authors: Bhattacharjya
authors: Bengang
authors: B
authors: Xing
mesh_terms: D000577:Amides / Q000737:chemistry; D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001422:Bacterial Adhesion / Q000187:drug effects / Q000528:radiation effects; D019281:Dimerization; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000528:radiation effects; D006090:Gram-Negative Bacteria / Q000166:cytology* / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D042541:Intracellular Space / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects* / Q000528:radiation effects; D057054:Molecular Imaging / Q000379:methods*; D008969:Molecular Sequence Data; D017319:Photosensitizing Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011524:Protoporphyrins / Q000737:chemistry*
chemical_list: D000577:Amides; D023181:Antimicrobial Cationic Peptides; D008070:Lipopolysaccharides; D017319:Photosensitizing Agents; D011524:Protoporphyrins; C028025:protoporphyrin IX