New technology can revitalize the bactericidal effects of conventional antibiotics in MDR E.coli infections

A research team led by Professor Kelvin Young Wai-Kook from the Department of Orthopedics and Traumatology, School of Clinical Medicine, LKS School of Medicine, University of Hong Kong (HKUMed) designed a non-invasive technique to activate its bactericidal effects. Conventional antibiotics in multidrug resistance (MDR) Escherichia coli (E. coli)Associated deep tissue infections, such as infections of the urinary tract and peritoneum.

In the study, MDR E. coli bacteria were again found sensitive to the intervention of conventional antibiotics when the bacteria were exposed to a moderately hyperthermic state (around 50°C). Hence, the HKUMed team designed a new microwave-responsive micro-shell encapsulated with conventional antibiotics that can achieve in situ hyperthermia treatment and antibiotic therapy simultaneously. The result was published in advanced functional materials.

background

Among all MDR bacteria, MDR E. coli, defined as Gram-negative bacteria, was one of the three critical priority pathogens identified by the World Health Organization (WHO). Due to its unique outer membrane (OM) structure, the bacteria can immunize themselves to treat most antibiotics available in clinics.

In short, a certain barrier is present in the chassis, which is the barrel assembly machine (BAM complex). When this compound combines with two other barriers to the MDR efflux pump and enzymatic degradation in the cytoplasm, the bacteria can effectively block the antibiotic attack. However, conventional treatment can only impair the function of the BamA protein (the main component of the BAM complex) rather than all three barriers at the same time.

Research method and results

The HKUMed research team discovered for the first time that these barriers would be temporarily paralyzed if the injury site temperature was raised to around 50°C for only 10 minutes, when human tissues can withstand this mild, short-term heat treatment.

When conventional antibiotics can intervene at the same time, the team believes that infections caused by Gram-negative bacteria can be completely eradicated. Hence, they design a new microwave-responsive microshell consisting of an FDA-approved biopolymer called poly(lactic-co-glycolic acid) (PLGA) that can generate mild heat subject to microwave signal stimulation.

When applied in situ microwave warming (MWH) strategy, MDR E.coli can be effectively re-sensitized to conventional antibiotic treatments such as β-lactam, aminoglycoside and tetracycline.

The results demonstrated that MWH induced structural disruption of the BAM complex, functional obstruction of MDR efflux pumps, and catalytic paralysis of related glycolytic or modulatory enzymes. Also, the treatment efficacy of this collective antibacterial strategy has been demonstrated in animal models with urinary tract infection and peritoneal infection.

research importance

We are inspired by the mechanism of fever in the human body, when a person is fighting a bacterial infection. We then discover that heat may help break through the barriers built by MDR E. coli. When MWH combines with the use of commercially available antibiotics, this approach can significantly reduce the burden of Gram-negative bacterial infection (eg, MDR E. coli) in deep tissue. We may also consider encapsulation of antitumor drugs with antibiotics to treat bone cancer patients with post-operative bacterial infection in future practice.. “

Kelvin Young Wai-Kook, Professor, Department of Orthopedics and Traumatology, School of Clinical Medicine, LKS School of Medicine, University of Hong Kong

source:

University of Hong Kong

Journal reference:

Mao, C., and others. (2022) Multidrug resistance Escherichia coli By compromising BAM biogenesis and enzymatic catalysis through microwave hyperthermia treatment. advanced functional materials. doi.org/10.1002/adfm.202202887

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