Fluorescent antibiotics for real-time tracking of pathogenic bacteria

Abstract

The harm of pathogenic bacteria to humans has promoted extensive research on physiological processes of pathogens, such as the mechanism of bacterial infection, antibiotic mode of action, and bacterial antimicrobial resistance. Most of these processes can be better investigated by timely tracking of fluorophore-derived antibiotics in living cells. In this paper, we will review the recent development of fluorescent antibiotics featuring the conjugation with various fluorophores, and focus on their applications in fluorescent imaging and real-time detection for various physiological processes of bacteria in vivo.

Keywords: Fluorescent antibiotics; Fluorescent imaging; Fluorophore; Live-cell tracking; Pathogenic bacteria.

Graphical abstract

Fig. 1

Structure of various antibiotics and fluorophores. NBD: nitrobenzofurazan, DMACA: 7-(dimethylamino)-coumarin-4-acetic acid, BODIPY: dansyl,boron-dipyrromethene.

Fig. 2

Super resolution imaging with different fluorescent antibiotics. (A) Structure of NBD-derived fluorescent antibiotic 4C-Tz-NBD [47]. SR-SIM fluorescence imaging of (B) S. aureus, (C) wild type E. coli, and (D) ΔtolC E. coli. And cross section of fluorescent imaging of (E) wild type E. coli and (F) ΔtolC E. coli: green, 4C-Tz-NBD; red, FM4-64FX; blue, Hoechst 33342. (G) Structures of fluorescent antibiotics Boc-FL and Ceph C-T [76]. 3D-SIM super-resolution microscope imaging of (H) B. subtilis and (I) S. pneumoniae IU 1945 PBPs after dual labeling with Ceph C-T (red) and Boc-FL (green) in live cells. NBD: nitrobenzofurazan, SR-SIM: super-resolution structured illumination microscopy, PBPs: penicillin-binding proteins.

Fig. 3

(A) Near-infrared fluorescent antibiotic vanco-800CW [39] and (B) its real-time imaging of bacterial infections in living mice. Left side: bioluminescence imaging; right side: fluorescence imaging (excitation 745 nm, emission 840 nm).

Fig. 4

Schematic representation of ratiometric signal generation process of CCF2 probe while degrated by β-Lactamase.