Antibiotics vs Bacteria: Which Will Win the War?
20th December 2022 - Last modified 18th October 2023
20 years of Alto. 20 years of science. #18
As part of Alto Marketing’s 20 year celebrations, we’re looking back at some of the most important advances in science over this time in our blog series “20 years of Alto. 20 years of science.” Here, we talk about the war between antibiotics and antibiotic resistant bacteria, and the discoveries that scientists have made that could help antibiotics come out on top.
Antibiotics are at constant war with bacteria, which continuously evolve to become resistant to the antibiotic. This has become a huge global problem of the 21st century, triggered by the increasing use of antibiotics to treat human infections.
Antibiotic resistance continues to grow, with drug-resistant bacterial infections now resulting in more than 700,000 annual deaths worldwide [1].
But fear not, knowledge can be used as power to help win the war against antibiotic resistant bacteria. This blog will take a closer look at how this issue has arisen, before delving into a description of the novel antibiotics that have been developed to overcome antibiotic resistance.
Antibiotics and antibiotic resistance: nature’s weapons for microbial warfare
Antibiotics are naturally produced by microorganisms such as fungi and bacteria. They are vengeful weapons that seek to kill and destroy bacteria.
To protect themselves, bacteria have developed mechanisms of antibiotic resistance. These act as defensive shields that are genetically programmed into the bacteria, which can be inherited by offspring and even transferred to other bacteria in a process known as horizontal gene transfer. This allows for the rise of antibiotic resistant bacterial armies.
It’s a constant battle of microbes deploying antibiotics as weapons, and bacteria evolving antibiotic resistance for protection. This occurs naturally in the wild and keeps different types of microbes in check.
The rise of superbugs
In 1928, humans discovered the bacterial fighting power of antibiotics. It was Alexander Fleming in St Mary’s Hospital Medical School, London who famously discovered the antibiotic penicillin.
Fleming noticed that a blue/green mould (now known as Penicillium) that incidentally grew on a petri dish had the ability to kill Staphylococcus bacteria. Since then, we have discovered many more antibiotics, and have used these to treat all types of bacterial infections. And this is where the real problems of antibiotic resistance began.
Naïvely, we thought that antibiotics were our silver bullet to bacterial pathogens. But we’ve used them in such quantities and concentrations that we’ve shot ourselves in the foot. In fact, in the 60 years since their introduction, millions of metric tons of antibiotics have been produced and used [2].
Now, the planet is awash with antibiotics, which has inevitably led to the selection of resistant strains. Through overuse and misuse, we’ve enforced an unrelenting selection pressure on bacteria to create drug resistant bacterial strains.
Bacterial battalions are growing in strength and numbers
Erythromycin was one of the earliest antibiotics to show warning signs of antibiotic resistance problems. This antibiotic was introduced as an alternative to penicillin for the treatment of infections in Boston City Hospital in the 1950’s.
Erythromycin was withdrawn after less than a year. Why? Because more than 70% of certain Streptococcus isolates are known to be erythromycin resistant [3].
However, this process has happened over and over again with every antibiotic brought to the market. We’ve now created superbugs – with resistance to our entire arsenal of antibiotic types.
And worryingly, these antibiotic resistant bacterial armies are growing in numbers, causing a rise in the number of bacterial infections that are unable to be treated with drugs. This has increased the burden of infections on healthcare, with prolonged hospital stays, and sadly, an increased number of deaths.
“Smart” antibiotics – could this new generation of drugs be enough to win the war against antibiotic resistance?
Although the antibiotic crisis is alive and kicking, scientists won’t stop until this crisis is averted. Several novel types of antibiotics have been under development over the last few years. This is certainly promising, as standard practices to control antibiotic resistance – including stricter antibiotic usage and improved hygiene – aren’t enough to control the issue.
These novel types of antibiotics are referred to as “smart” antibiotics. Including phages and nano antibiotics, these smart antibiotics cleverly subvert mechanisms of antibiotic resistance to render the bacteria powerless. Smart antibiotics may just be what it takes to win the war against antibiotic resistance.
Phages: tiny bacterial hitmen
Phages (also known as bacteriophages) are a type of virus that infect and replicate inside bacteria. Although these are microorganisms rather than drugs, they are smart antibiotic agents that make pretty decent replacements for traditional antibiotics. These space-age looking viruses hijack bacterial genomes to make thousands of copies of themselves, eventually causing the bacterial cells to die and burst open, releasing phages that go on to infect more bacteria. Pretty amazing stuff, right?
Unlike conventional antibiotics, which go on an unpremeditated killing spree, phages are refined, expert hitmen that only target the type of bacteria that you’ve hired them for. This means that bacteriophages can effectively treat bacterial infections while the lovely, healthy bacterial flora in other parts of your body are left alone.
Phages have shown promising results in clinical trials for the targeted treatment of several types of bacteria, including species associated with cystic fibrosis [4], UTIs [5], and pancreatitis [6].
Despite its advantages, the targeted approach of phages also has its downsides. For instance, if you don’t know exactly what bacterial pathogen is causing the infection, you can’t select an appropriate phage. This can be a time-consuming process that delays treatment.
Nano antibiotics: tiny weapons of bacterial destruction
These are antibiotic delivery systems consisting of metal nanoparticles. Intricately engineered nanoparticles contain sharp flakes made of graphene on their surface.
Antibiotics are loaded onto the graphene flakes, which pierce the thick, protective layer of bacteria for improved antibiotic delivery. As several mechanisms of antibiotic resistance revolve around preventing the entry of drugs into the bacteria, nano antibiotics might just be the weapon we are looking for in the fight against antibiotic resistance.
Nano antibiotics have shown the ability to kill the superbug MRSA [7], which is resistant to several types of drugs, and is a large concern in hospitals due to its ease of spread and mortality rate.
However, concerns surrounding the toxicity of nano antibiotics have been raised from the long-term exposure to metallic and carbon-based structures. More extensive testing on mammalian cells is required before these engineered antibiotics can be used in clinical trials.
Antibiotics may have lost the battle, but will they win the war?
Despite the worrying growth of antibiotic resistance over the past few decades, a new generation of antibiotics are on the cusp of being manufactured for deployment. These technologies may just be what it takes to fight the war against drug resistant superbugs, putting an end to this problem for good.
References
(1) Baekkeskov, E., Rubin, O., Munkholm, L. and Zaman, W., 2020. Antimicrobial Resistance as a Global Health Crisis. In Oxford Research Encyclopedia of Politics.
(2) Chandel, A.K., Rao, L.V., Narasu, M.L. and Singh, O.V., 2008. The realm of penicillin G acylase in β-lactam antibiotics. Enzyme and Microbial Technology, 42(3), pp.199-207.
(3) Desjardins, M., Delgaty, K.L., Ramotar, K., Seetaram, C. and Toye, B., 2004. Prevalence and mechanisms of erythromycin resistance in group A and group B Streptococcus: implications for reporting susceptibility results. Journal of clinical microbiology, 42(12), pp.5620-5623.
(4) Trend, S., Fonceca, A.M., Ditcham, W.G., Kicic, A. and Cf, A., 2017. The potential of phage therapy in cystic fibrosis: Essential human-bacterial-phage interactions and delivery considerations for use in Pseudomonas aeruginosa-infected airways. Journal of Cystic Fibrosis, 16(6), pp.663-670.
(5) Zalewska-Piątek, B. and Piątek, R., 2020. Phage therapy as a novel strategy in the treatment of urinary tract infections caused by E. coli. Antibiotics, 9(6), p.304.
(6) Schooley, R.T., Biswas, B., Gill, J.J., Hernandez-Morales, A., Lancaster, J., Lessor, L., Barr, J.J., Reed, S.L., Rohwer, F., Benler, S. and Segall, A.M., 2017. Development and use of personalized bacteriophage-based therapeutic cocktails to treat a patient with a disseminated resistant Acinetobacter baumannii infection. Antimicrobial agents and chemotherapy, 61(10), pp.e00954-17.
