Introduction

Antimicrobial resistance (AMR) is one of the biggest global threats to public health and development. According to a new study, bacterial AMR was directly responsible for 1.27 million global deaths and contributed to 4.95 million deaths in 2019. An analysis on antimicrobial resistance published in 2016 estimated that this number could reach 10 million by 2050.

Antimicrobial resistance (AMR) is the reduced effectiveness or inability of an antimicrobial agent to inhibit the growth of bacteria, potentially leading to therapy failure, especially in the case of pathogenic organisms. Bacterial strains can develop resistance through various ways, such as genetic mutations, the acquisition of external genes from other bacteria through horizontal transfer, or the activation of genetic processes that induce the expression of resistance mechanisms. The development of resistance can be triggered by several factors, including the improper use of antimicrobials in human and veterinary medicine, inadequate hygiene practices in healthcare settings or in the food chain, which facilitate the transmission of resistant microorganisms. These factors contribute to the diminishing effectiveness of antimicrobials.

The antimicrobial agents used in food-producing animals and in human medicine in Europe are frequently the same or belong to the same classes. The use of antimicrobials in both humans and animals, might result in the development of AMR, which results from the continuous positive selection of resistant bacterial clones, whether these are pathogenic, commensal or even environmental bacteria. This will change the population structure of microbial communities with serious consequences for human and animal health.

Plasmid transfer

Antimicrobial resistance is a major threat to humanity due to widespread plasmid transfer via conjugation. Understanding plasmid transfer is essential for limiting resistance spread. Modeling of plasmid transfer is essential to uncovering the fundamentals of resistance transfer and for the development of predictive measures to limit the spread of resistance. One of the main limitations in the current understanding of plasmids is the lack of knowlegde of the conjugative DNA transfer mechanisms, which conceals the true role of plasmid transfer in nature.

In a study, scientists utilized DNA structure analysis to identify plasmid transfer substrates, surpassing sequence-based methods. Thousands of potential substrates were found, indicating higher plasmid mobility across species than previously known. Over half of the mobile plasmids could be mobilized by different conjugation systems, forming a robust network. This network may facilitate transfer of resistance from the environment to human pathogens, driving antibiotic resistance. Future studies and prevention measures should focus on this network.

The most important pathogens in human perspective

In 2020, Campylobacteriosis was the most frequently reported zoonotic disease in the EU and the leading cause of foodborne illnesses. Campylobacter can be found in both humans and poultry, displayed significant resistance to the fluoroquinolone antibiotics, commonly used to treat certain bacterial infections in humans. Increasing resistance to fluoroquinolones was observed in both humans and broiler chickens infected with Campylobacter jejuni, as well as in the most prevalent type of Salmonella, Salmonella Enteritidis. These resistance in animals ranged from moderate to high. While resistance to tetracyclines and ampicillin in Salmonella decreased in several countries between 2016 and 2020, it remained high in both human and animal bacteria

Mcr-producing Salmonella enterica isolates from 37 countries across five continents reveal the presence of strains carrying carbapenem and tigecycline resistance genes. However, a significant decline in the prevalence of extended-spectrum β-lactamase (ESBL)-producing E. coli was observed in over half of EU countries among food-producing animals, which is a positive development since certain ESBL-producing E. coli strains can cause serious human infections. Notably, carbapenem resistance in E. coli and Salmonella from food-producing animals was exceedingly rare, which is crucial since carbapenems are considered last-resort antibiotics. Any emergence of resistance to carbapenems in zoonotic bacteria is a cause for concern. Interactive data about the resistance level of different countries are shown here.

Summary regarding the antimicrobial resistance of Campylobacter spp. in the UK are also available. In summary C. jejuni and C. coli bacteria from chicken samples in the UK commonly showed resistance to ciprofloxacin, nalidixic acid, and tetracycline. However, the resistance to erythromycin and streptomycin in the examined isolates was rare, and resistance to gentamicin was extremely rare. Since 2014 no significant increase in resistance has been observed.

Cow tank milk

An evaluation of the potential for antimicrobial resistance (AMR) development was conducted in relation to feeding calves with milk or colostrum from cows treated with antibiotics. The findings indicated that if an adequate duration between treatment and calving was provided, then there would be no significant rise in the excretion of antimicrobial-resistant bacteria in the faeces of calves. However, milk obtained from cows that received antimicrobial treatment while lactating exhibited substantial residual amounts during both the treatment phase and the subsequent withdrawal period. Consumption of such milk would result in an increase of antimicrobial-resistant bacteria in faeces of juvenile bovine. Such selection for antimicrobial-resistant bacteria may have negative consequences on global public health. In order to mitigate the risk for the development of AMR the following options were presented. Prohibiting the use of milk from treated cows, decreasing the antimicrobial concentration by fermentation, filtration or by increasing the pH. The potential of thermal activation was also suggested through heat treatment.

The relationship of raw dog food and AMR

New research presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) reveals that raw dog food, commonly sold in supermarkets and pet shops, contains antibiotic-resistant bacteria, posing a significant global public health threat. Scientists from the University of Porto found that 54% of tested dog food samples contained Enterococcus bacteria (E. faecalis, E. faecium), with more than a third of these strains showing resistance to multiple antibiotics. Notably, 2% of isolates were resistant to vancomycin and teicoplanin and 23% were resistant to linezolid, an antibiotic of last resort. Some antibiotic-resistant bacteria in the dog food matched strains found in European hospitals, suggesting that feeding dogs raw food might contribute to the spread of antibiotic-resistant bacteria. The study underscores the urgency of addressing antibiotic resistance, which is already a major public health concern worldwide. The researchers call for increased awareness and regulation to mitigate this risk.

The role of mercury and pesticides

A study examined the impact of historical mercury (Hg) contamination on antibiotic resistance genes (ARGs) in agricultural soils. The researchers investigated the ARG profile in paddy and upland soils with different cropping systems and assessed their connection to legacy Hg exposure. The findings revealed that the ARG profiles varied significantly between paddy and upland soils. However, both types of soils with long-term Hg contamination had higher diversity and abundance of ARGs compared to non-polluted soils. The co-occurrence network analysis demonstrated significant associations among Hg, Hg resistance genes, mobile genetic elements (MGEs), and ARGs. Path analysis suggested that legacy Hg could potentially affect soil resistomes by influencing soil microbiota, Hg resistance genes, and MGEs, leading to elevated levels of ARGs through co-selection. Redundancy analysis further supported a significant association between legacy Hg pollution and ARG variations in both paddy and upland soils. In conclusion, the study highlights the overlooked role of legacy Hg as a persistent selecting agent that contributes to the presence of soil ARGs in agroecosystems.

Methods to reduce or prevent AMR

Antimicrobial resistance (AMR) is a serious threat to global public health and requires immediate, preferably long-term action. Current drug treatments, phage therapies cannot fully contain this threat, as microbes are able to circumvent the mechanisms of action of drugs/phages. One of the newest solutions is the use of peptides as drugs, as antimicrobial peptides offer remarkable advantages over antibiotics.

Any peptide that effectively kills bacteria is called an antimicrobial peptide. The utilization of these peptides in bactericidal applications is a subject of scientific research, as it is said that peptides represent a potentially superior approach compared to bacteriophages. This is attributed to the mechanism by which peptides act, disrupting the bacterial cell envelope, reducing it to adapt resistance, and interfacing with the cellular membrane.

Researchers expect to be able to develop specific peptides that could kill a wide range of bacteria. As bacteria are likely to be resistant to these peptides over time, new antibiotics and better phage therapy will also need to be developed, but most importantly the overuse of antibiotics should generally be avoided.