Antimicrobial resistance (AMR) has been declared to be a major global health crisis by the World Health Organization (WHO) and has been predicted to cause 10 million deaths by the year 2050.
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The use of nanotechnology to detect AMR would be revolutionary for preserving human health, with many nanomaterial platforms providing approaches that are more advanced than conventional AMR diagnostic strategies.
Background
Antimicrobial resistance (AMR) can emerge due to evolving pathogens such as bacteria and viruses, which stop responding to medicinal drugs, preventing effective treatment of infections.
The alarming spread of multi-resistant bacteria referred to as ‘superbugs’, such as MRSA, cause infections that are difficult to treat with antibiotics. Multidrug-resistant Staphylococcus aureus (MRSA) infections have been reported by the Center for Disease Control and Prevention (CDC) to have increased between the years 1999 and 2005, from 127,000 to 278,000 cases, with the level of associated mortality also increasing from 11,000 to 17,000.
Preventative measures, however, positively influenced the decline of this superbug; however, antimicrobial resistance is still a great concern, especially due to factors such as the overuse of antibiotics.
The total consumption of antibiotics in 2020 has been estimated to be over 4.5 trillion doses, 24% higher than 2015, which has resulted in an expenditure of 1.4 trillion dollars.
Antimicrobial Resistance
AMR can be categorized as being either an intrinsic occurrence or acquired externally. Intrinsic AMR can be described as a natural phenomenon, where the Gram-negative bacteria demonstrate a reduced level of permeability of antibiotics as a result of their complex outer layer. Acquired AMR consists of acquiring resistance genes from already-resistant bacteria through conjugation or due to chromosomal gene mutations.
Antimicrobial resistance has become a priority for WHO and global researchers due to the negative impact this can cause to patients suffering from infections that cannot be treated due to multidrug resistance – this means the pathogen at the root of their infection cannot be treated effectively by a range of drug candidates.
Detection of AMR
The detection of antimicrobial resistance has become a novel, innovative development by researchers to address this major health crisis affecting global human health.
Rapid detection of AMR aims to provide critical information about the presence of antimicrobial resistance in patients to prevent the improper use of antibiotics, which would be ineffective as well as prevent any further fuel to AMR properties present in bacteria.
While the development of a rapid detection device would be revolutionary for the advancement against the AMR crisis, there are challenges associated with current molecular strategies that may be limiting for this new venture.
Challenges with Current Detection Methods
Current molecular methods can have challenges that may prove to be obstacles against the development of AMR detection approaches, including high time consumption, from sample preparation to result, which may have a long turnaround time of approximately 72 hours.
Additionally, the complexity of this process, which would require costly and sophisticated equipment as well as trained employees is also challenge, as this would further complicate the process.
Solving these obstacles may be significant for rural areas as well as low-income countries, where accessing AMR diagnoses may be more difficult, furthering the progression of infections within AMR patients, as well as morbidity and mortality.
However, the use of nanotechnology may be an innovative approach to addressing the current obstacles facing the development of rapid detection devices.
Nanotechnology-Based AMR Diagnostics
Nanotechnology has provided the potential to develop a powerful detection platform that is highly sensitive and affordable while also providing fast results.
The use of nanoparticles for pathogen detection has been covered in numerous studies within the literature due to their nanoscale size of 1 and 100 nm. This key characteristic is beneficial in many ways. It provides other advantages such as having a high surface area to volume ratio, high reactivity, surface functionalization, which can aid with precise targeting, and good electrical, magnetic and optical features.
Nanosenors that utilize nanomaterials can be beneficial for this innovative detection system, with researchers investigating nanoparticles that can undergo selective aggregation, which can be used to identify the presence of pathogens.
Gold nanoparticles are a type of metallic nanoparticle that has been proven to be useful in many biomedical applications and can be used as a nanosensor due to modulation of their optical properties, resulting in a color change. This can be useful for developing visual sensors for AMR diagnostics, as supported by a study using gold nanoparticles to detect a particular strain of multidrug-resistant Salmonella typhimurium.
The gold nanoparticles within this study functioned to bind to the surface of the bacteria, causing aggregation of the nanoparticles, resulting in a color change from purple to grayish. The presence of the drug-resistant bacteria was detected, illustrating the potential nanoparticles can have in detecting antimicrobial resistance pathogens.
Translational Significance
Nanotechnology has become associated with advancements in many fields and is very versatile for use within a range of applications. The use of this field for the development of antimicrobial resistance holds great potential, as this approach may enable early diagnosis of AMR infections, allowing for effective treatment in patients, as opposed to improper use of antibiotics at a late stage of infection.
Additionally, the development of a rapid, affordable, point-of-care device would be revolutionary for areas that are low-income as well as remote to ensure efficient healthcare is accessible to all.
However, challenges such as the most effective nanotechnology approach are still being investigated, with organic nanoparticles found to perform better than magnetic and silica nanoparticles, which can be toxic to bacteria. These have been found to cause false-positive results, rather than providing accurate results on the resistance against antibiotics. Gold nanoparticles have also been shown to have effective results for use as a potential candidate for AMR diagnostics.
With further research into laboratory samples and animal models, the use of a miniature rapid diagnostic device that accurately detects AMR pathogens may be developed, progressing WHO research objectives against antimicrobial resistance.
References and Further Reading
WHO.(2021) Antimicrobial resistance. [online] Available at: https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance
Saxena S, Punjabi K, Ahamad N, Singh S, Bendale P, Banerjee R. (2022) Nanotechnology Approaches for Rapid Detection and Theranostics of Antimicrobial Resistant Bacterial Infections. ACS Biomaterials Science & Engineering. https://pubs.acs.org/doi/abs/10.1021/acsbiomaterials.1c01516
Webster T, Seil I. (2012) Antimicrobial applications of nanotechnology: methods and literature. Int J Nanomedicine. 2767. https://doi.org/10.2147/ijn.s24805
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