Lipopolysaccharide Neutralizing
Peptide–Porphyrin
Conjugates for Effective Photoinactivation and Intracellular Imaging
of Gram-Negative Bacteria Strains
posted on 2016-02-20, 14:31authored byFang Liu, Annie Soh Yan Ni, Yingjie Lim, Harini Mohanram, S. Bhattacharjya, Bengang Xing
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.