Cyclodextrins to control bacteriophages infection in biotechnology

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In the biotechnology industry one of the biggest threats for bacteria-driven bioreactors is the infections caused by enemies of bacteria, the bacterial viruses, called also bacteriophages. More than 70% of biotech companies are admitted to encountering this problem.

Infection of bacterial cultures by bacteriophages as well as prophage induction in the host cells are serious problems in both research scale methods and biotechnological production facilities. The common prevention strategies (such as good laboratory/factory hygiene, sterilization, decontamination and disinfection) are necessary to avoid bacteriophage contamination.  However, it is well known that no matter how good the laboratory/factory practice and hygiene are, bacteriophage infections do occur from time to time.

Despite the fact that phage infections are such a dangerous and widespread risk, to date, there are no generally applicable, efficient methods to avoid such contaminations.

In a recent paper (1) a convenient and effective way to control bacteriophages’ activity was presented by using peptide-grafted compounds. These peptide-decorated substances were found to irreversibly deactivate bacteriophages, while they remain safe for bacteria and mammalian cells in the bioreactors. As for the structure of these active compounds, they consist of a core (a cyclodextrin or a gold nanoparticle) both coated with a hydrophobic alkyl chain terminated with a peptide „antenna” which is selective for the given bacteriophages. This approach enables irreversible deactivation of the wide range of T-like phages (including the most dangerous in phage infections, phage T1) under ambient conditions, at 37 °C within 1 hour. (see Figure 1)

The paper clearly demonstrate that these peptide-tagged compounds can be used directly inside the environment of the bioreactor, but they are also a safe additive to stocks of antibiotics and expression inducers (such as isopropyl- beta-D-1-thiogalactopyranoside, i.e., IPTG) that cannot be autoclaved and are a common source of phage infections.

Figure 1. Illustration of the deactivation of bacteriophages by peptide-decorated gold nanoparticle and beta-cyclodextrin.

(1) Lukasz Richter et al : Peptide-grafted nontoxic cyclodextrins and nanoparticles against bacteriophage infections. ACS Nano 2022 16 11 18990-19001.

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