Biosensor applications in the field of antibiotic research--a review of recent developments

Abstract

Antibacterials are among of the most important medications used in health care. However, their efficacy is increasingly impeded by a tremendous and globally spread bacterial resistance phenomenon. This bacterial resistance is accelerated by inadequate application of antibacterial drugs in humans, the widespread veterinary use of antibacterials, and antibacterial occurrence in the environment and food. Further, there is a lack of development of innovative novel drugs. Therefore, the search for novel antibacterials has to be intensified and the spread of antibacterials in the environment has to be restricted. Due to the fundamental progress in biosensor development and promising applications in the antibiotic field, this review gives for the first time an overview on the use and prospects of biosensor applications in that area. A number of reports have applied biosensors of different design and techniques to search for antibacterials in environmental and foodstuff matrices. These studies are discussed with respect to the analytical values and compared to conventional techniques. Furthermore, biosensor applications to elucidate the mode of action of antimicrobial drugs in vitro have been described. These studies were critically introduced referring to the informational value of those simulations. In summary, biosensors will be illustrated as an innovative and promising, although not yet comprehensively applied, technique in the antibacterial field.

Keywords: antibacterials; antibiotics; bacterial resistance; biosensor.

Figure 1.

Progress of selected resistant bacterial strains in Central and Southern Europe between 2002 and 2009. The amount of resistant isolates increased slowly but constantly over the years.

Figure 2.

The timeline of antibacterial development modified from Wright [7]. Antibacterial development started in the 1930s with the sulfonamides, followed by a period of 40 years with successful antibacterial discovery. After a long period in which no real novel antibacterials were discovered, only a few new antibacterial classes were identified in the current millennium.

Figure 3.

Biosensor applications in the antibacterial field are classified regarding to (A) their experimental approaches, and (B) the detection principles. (A) Nearly 60% of the biosensor applications contribute to detection or quantification of antibacterials in the environment as a basis for interference with the increasing bacterial resistance; (B) Nearly half of the detection principles are based on surface plasmon resonance technique.

Figure 4.

(A) SPR image of antibody binding onto different immobilized antibiotics (neomycin/NEO, gentamicin/GNT, kanamycin/KAN, dihydrostreptomycin/DHS, norfloxacin-NH₂ derivative/NOR-NH₂, chloramphenicol/CAP, and sulfamethazine/SMZ. (B) Sensorgramms display specific antibody recognition with low cross reactivity (reprinted with permission from Rebe Raz, S.; Bremer, M.G.E.G.; Haasnoot, W.; Norde, W. Label-free and multiplex detection of antibiotic residues in milk using imaging surface plasmon resonance-based immunosensor. Anal. Chem. 2009, 81, 7743–7749. Copyright © 2009, American Chemical Society).

Figure 5.

Illustration of SAW measurements. The changes in phase (A) and amplitude (B) of surface acoustic waves confirmed the lipid II recognition (dotted line in (A)) in parallel to gallidermin membrane insertion and a resulting membrane rigidification (increase in amplitude in (B) at the dashed or dotted line, resp.) (reprinted with permission from Al-Kaddah, S.; Reder-Christ, K.; Klocek, G.; Wiedemann, I.; Brunschweiger, M.; Bendas, G. Analysis of membrane interactions of antibiotic peptides using ITC and biosensor measurements. Biophys. Chem. 2010, 152, 145–152. Copyright © 2010, with permission from Elsevier).

Figure 6.

Biosensors’ contribution to the mode of action studies of gallidermin. Whereas the biosensor techniques QCM and SAW allow for the detection of binding kinetics (targeted and untargeted), additional techniques like ITC were necessary to provide evidence for non-targeted membrane activities of gallidermin in synergy with lipid II mediated interactions (reprinted with permission and minor modifications from Al-Kaddah, S.; Reder-Christ, K.; Klocek, G.; Wiedemann, I.; Brunschweiger, M.; Bendas, G. Analysis of membrane interactions of antibiotic peptides using ITC and biosensor measurements. Biophys. Chem. 2010, 152, 145–152. Copyright © 2010, with permission from Elsevier).