Antimicrobial resistance (AMR) is an increasingly serious global problem, causing more than 1 million deaths worldwide every year. The ability of bacteria, viruses, fungi, and parasites to develop resistance to antibiotics poses one of the most serious challenges to modern medicine.
A study published in The Lancet in September 2024 predicts that over 39 million people could die from antibiotic-resistant infections by 2050. Conducted by the Global Research on Antimicrobial Resistance (GRAM) Project, the research analysed the evolution of AMR between 1990 and 2021, providing worrying predictions for the coming decades. The study examined 204 countries, revealing a growing trend that could escalate into a global health crisis if urgent action is not taken.
However, recent research published in Nature could mark a significant turning point in tackling this threat to health. Lariocidin, a potent new antibiotic derived from soil bacteria, may offer a solution for treating strains that are resistant to commonly used antibiotics.
An old resource, a new discovery
Lariocidin was discovered in soil samples collected from a lab technician’s garden. Researchers from McMaster University (Canada) and the University of Illinois (Chicago) analysed soil bacteria over a long period of time and, after a year of study, identified a micro-organism belonging to the genus Paenibacillus, capable of naturally producing a new antibiotic, lariocidin, which has the ability to inhibit protein synthesis in bacteria.
Lariocidin acts by binding directly to the ribosome, the cellular ‘factory’ that produces proteins. By interfering with this fundamental process, the molecule prevents bacteria from correctly synthesising their proteins, hindering their growth and replication.
Resistant to resistance
One of the most promising features of lariocidin is its ability to avoid the common antibiotic resistance mechanisms developed by bacteria. Moreover, this antibiotic is not toxic to human cells, a crucial aspect for its potential therapeutic use.
Experiments have shown lariocidin to be surprisingly effective in treating serious infections, confirming its potential as a new weapon in the fight against difficult-to-treat bacterial infections.
So, have we found a solution to AMR? Not quite. We spoke to Gianpiero D’Offizi, lecturer in Gastroenterology at UniCamillus University who is also an expert in allergology and infectious diseases.
Could you explain what causes antimicrobial resistance?
“Antimicrobial resistance (AMR) is one of the biggest health challenges worldwide. Many infections caused by different pathogens are becoming increasingly difficult to treat with commonly available antibiotics. This complicated situation is caused by several factors. When bacteria are exposed to antibiotics, they develop defence mechanisms that enable them to survive and multiply despite being treated with medicines designed to kill them.
The main causes of this problem include:
- Excessive use of antibiotics. Frequent and sometimes inappropriate use of antibiotics in the medical, agricultural and veterinary fields can favour the selection and spread of resistant bacteria.
- Inappropriate dosages and duration of treatment. Taking antibiotics in insufficient doses or for too short time periods does not completely eliminate bacteria, allowing the most resistant strains to survive and multiply.
- Poor hygiene and inadequate infection control. Poor hygiene measures in hospitals, clinics and laboratories encourage the spread of resistant bacteria among patients and healthcare personnel.
- Global movement of people and goods. International travel and global trade facilitate the spread of resistant bacteria from one country to another, thus making the problem global.
- Genetic mutations and gene transfer. Bacteria can acquire resistance through spontaneous mutations or through the transfer of resistance genes from other bacteria, whether of the same strain or a different one.
The combination of these factors contributes to the rapid spread of antibiotic resistance, making it increasingly difficult to treat bacterial infections with currently available medications”.
Which infections and pathogens are most resistant to common antibiotics?
“The most common infections that can become resistant to antibiotics are:
- Urinary tract infections. Urinary tract infections (UTIs) are among the most common. The main causative agents are Escherichia coli, Klebsiella pneumoniae and Enterococcus spp, but strains of E. coli that are resistant to fluoroquinolones and β-lactams are becoming increasingly prevalent, which reduces the effectiveness of these medications for many patients.
- Respiratory infections. Many respiratory infections, including pneumonia, are caused by Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus. The resistance of S. pneumoniae to penicillin and H. influenzae to cephalosporins is of particular concern. Additionally, the spread of methicillin-resistant Staphylococcus aureus (MRSA) complicates the treatment of skin and respiratory infections.
- Gastrointestinal infections. Clostridium difficile is a pathogen that causes colitis and severe diarrhoea, which is often associated with antibiotic use. C. difficile is becoming increasingly resistant to metronidazole and vancomycin. Salmonella and Campylobacter, which are commonly associated with foodborne infections, are becoming resistant to fluoroquinolones and tetracyclines.
- Skin and soft tissue infections. These are often caused by Staphylococcus aureus and Streptococcus pyogenes. MRSA is a major issue in these infections, as it is resistant to many first-line therapeutic options. Pseudomonas aeruginosa, a pathogen associated with chronic wound infections, also shows resistance to many antibiotics, including aminoglycosides and carbapenems.
- Hospital-related infections. Hospital-acquired infections pose a significant threat to public health. Acinetobacter baumannii and Enterobacteriaceae, including Klebsiella and Escherichia coli, often exhibit resistance to carbapenems and colistin, the last-line class of antibiotics. The resistance of these pathogens is particularly concerning as it affects vulnerable patients in clinical settings, where there is a high risk of transmission to others”.
Do you see MR causing millions of deaths in the coming decades? Based on the current state of research, do you think this trend can be reversed within a few years?
“Current research suggests that AMR could cause millions of deaths in the coming decades. The increasing resistance of pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Clostridium difficile, Salmonella, Campylobacter, Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae poses a significant threat to global health. According to studies and analyses carried out using predictive models, antibiotic resistance could become the leading cause of death by 2050, surpassing cancer and other chronic diseases. Without significant intervention, estimates suggest that resistant infections could cause up to 10 million deaths per year. The situation is further exacerbated by the fact that many last-line antibiotics are losing efficacy, which compromises their ability to treat complex infections. Currently, research on antibiotic resistance is very active and diverse. Researchers are exploring new classes of antibiotics, alternative therapies such as bacteriophages, and strategies to enhance the effectiveness of existing antibiotics. Additionally, they are investigating methods to prevent the formation of bacterial biofilms and modulate the microbiome in order to reduce the selection and spread of resistant pathogens. In order to reverse the trend of antibiotic resistance, coordinated global action is required. Possible solutions include:
- Strengthening research and development by investing significantly in the development of new antibiotics and alternative therapies.
- Antimicrobial stewardship programmes: antimicrobial stewardship (AMS) is a coordinated approach that aims to optimise antibiotic use, promote appropriate use, prevent bacterial resistance, and ensure the best possible clinical outcomes. AMS essentially involves a multidisciplinary team managing antibiotic use in a responsible and rational manner. Implementing AMS programmes to monitor and control antibiotic use in hospitals and communities is a priority.
- Public education: promoting public awareness of the appropriate use of antibiotics and the consequences of resistance.
- International collaboration: facilitating international collaboration between countries and organisations to share knowledge, resources, and strategies.
Tackling the threat of antibiotic resistance requires a global and sustainable commitment. By taking a collective and coordinated approach, we can hope to preserve the effectiveness of antibiotics and protect public health for future generations”.
What makes lariocidin so scientifically promising, and how does it differ from other antibiotics?
“Lariocidin is considered one of the most promising solutions in the fight against antimicrobial resistance. This innovative compound has caught the attention of scientists due to its unique features that set it apart from conventional antibiotics. Unlike conventional antibiotics, which generally interfere with cell wall synthesis or the replication of genetic material, lariocidin acts directly on the membranes of resistant bacteria, destroying them. This significantly reduces the likelihood of the bacteria developing resistance.
One of the most promising aspects of lariocidin is its ability to eliminate a wide range of resistant pathogens. Studies have shown that lariocidin can combat bacteria that are resistant to commonly used antibiotics such as methicillin and vancomycin, making it valuable for treating difficult infections. Lariocidin has a favourable safety profile, with fewer side effects than traditional antibiotics. This is particularly important for long-term treatment and for vulnerable populations, such as children and the elderly. Its specificity for pathogenic bacteria reduces the risk of disrupting the balance of the human microbiome. Additionally, due to its mechanism of action, lariocidin exhibits a lower propensity for bacterial resistance to develop. This characteristic could prolong its efficacy over time, reducing the need to develop new antibiotics in future.
The medicine is still in development, but the initial results are extremely promising. Lariocidin may represent a valuable alternative to existing antibiotics. Its efficacy against resistant pathogens and favourable safety profile makes it a valuable resource in the fight against antibiotic resistance. However, to comprehensively address the resistance crisis, continued investment in the research and development of increasingly innovative antibiotics is essential, in order to exploit their strengths and ensure public health protection in the fight against infections”.