Antibiotic-resistant microorganisms have already been covered on earlier occasions on Mysterious of Science, yet the issue is still crucial today. Bacteria have evolved and acquired resistance genes to antibiotics as a result of their indiscriminate and inappropriate use. Bacterial species are now resistant to up to 18 different antibiotics. These bacteria also live in places frequented by people who are not in the best of health to fight them if infected. These are hospitals or prisons, nursing homes, and places where people aren’t always in good health and, at times, aren’t always clean. Being admitted to a hospital nowadays is dangerous for any reason. The risk stems not only from the factor that caused us to be admitted to the hospital but also from the fact that living in a hospital increases the likelihood of developing an illness caused by a multi-resistant bacteria that is resistant to antibiotics. Scientific data indicates that regardless of the patients’ age range or comorbidities, 63% of all infections brought on by bacteria resistant to antibiotics take place in hospitals or other healthcare facilities.
The emergence of these germs poses a severe threat to public health since they have the potential to spread epidemically, killing hundreds or even thousands of people and sparking new pandemics like the most recent one brought on by COVID-19. Resistance to antibiotics is not a new phenomenon. It is almost as old as pathogenic bacteria themselves, as they have been combated by other organisms for hundreds of millions of years using natural antibacterial substances. Bacteria have evolved genes that allow them to resist antibiotic action in a variety of ways, including destroying antibiotic molecules or rapidly expelling them from their interior before they can act, among other ingenious possibilities.
The greatest significant therapeutic development in medicine is thought to have been Fleming’s discovery of penicillin. When one antibiotic ingredient was discovered, it paved the way for the discovery of many others, until we now have a wide variety of natural and synthetic antibiotics. However, since the 1940s, when antibiotics first became extensively employed, bacteria have developed a resistance to them and have learned to battle and defeat them. Even reported instances of bacteria becoming resistant to several antibiotic kinds have occurred. The Shigella bacteria that caused the epidemic of diarrhea that killed 12,500 people in Guatemala in 1968 contains a plasmid that confers resistance to four different antibiotics.
Mechanisms of resistance evolution
Antibiotics are certainly something you’ve taken more than once, stopping as soon as you felt better. This conduct, though extremely reasonable, why take a medication I don’t need? but increases the likelihood that the antibiotic will work less effectively the next time we take it to treat the infection. And it is true that bacterial resistance to antibiotics is a piece of the species’ evolution taking place right in front of our eyes. For individuals who are most vulnerable to their effects, the unfavorable conditions that bacteria are forced to endure in the presence of antibiotics are fatal. However, genetic variation exists in every community, even bacterial populations.
Figure 1. Antibiotics have been dubbed “wonder medications” with good reason, but after 70 years of usage and abuse, most antibiotic and bacterial combinations now experience higher rates of resistance. Credits: by Pexels from Pixabay
Not all bacteria respond to the antibiotic in the same way. When the medication is not given at increasing levels, the most resistant does not succumb and the most sensitive die first. Because we didn’t finish our antibiotic prescription, we only entirely eliminated the susceptible bacteria while leaving the resistant ones behind. Although our immune system can handle the issue, certain bacteria still manage to get outside of our body and wait to infect another organism. The same antibiotic won’t be as effective at eliminating such bacteria. A population of bacteria that is entirely resistant is chosen after several iterations of this cycle.
How did bacteria develop a resistance to antibiotics?
It is now acknowledged that when bacteria are exposed to unfavorable settings, they start hypermutation processes that result in genetic change but whose exact mechanism is unknown. The majority of the modified bacteria perish, but others have developed mutations in one or more genes that enable them to endure in this harsh environment. Once a bacterium possesses a gene for resistance to an antibiotic, all of its progeny will share that resistance. Even worse, bacteria can transmit genes “horizontally,” or between siblings, relatives, or even complete strangers, in addition to “vertically,” or from parents to children. It’s as if we could provide our pals who desired it if we had a gene that made us resistant to cancer. With bacteria, this is what takes place. Once a gene has been created via mutation that enables one organism to resist an antibiotic, it is then accessible to other bacteria that require it. Therefore, even if only one bacterium discovers a way to reproduce and survive, it is enough because even if it fails, the other bacteria will still be of the same species. Through bacterial populations, resistance spreads in this manner.
In addition to being used to treat illnesses in humans, antibiotics are frequently given to farm animals in order to keep them healthy and enable them to put on weight and produce more. These antibiotics penetrate the soil and kill the bacteria that live there, yet these bacteria may also develop resistance genes. These genes might be passed on to other bacteria that could harm us. It is not unexpected that bacteria resistant to many antibiotics are on the rise given the widespread and ongoing usage of antibiotics.
The search for the super antibiotic
Antibiotic resistance in bacteria is becoming an increasingly serious problem, according to the WHO. This is significant since previously curable diseases are now becoming fatal due to antibiotic resistance. Therefore, there is an urgent need to discover or invent new antibiotics to replace those rendered ineffective by bacterial evolution during the twentieth century and so far in the twenty-first. Moreover, understanding the molecular underpinnings of bacterial conjugation may help researchers create fresh strategies to contain the spread of antibiotic resistance. Several strategies are now being considered to combat bacteria that are resistant to antibiotics. Preventing the spread of antibiotic resistance genes is one of them, and it offers promise. As previously stated, one of the primary ways that harmful bacteria acquire antibiotic resistance is by receiving DNA from already resistant bacteria.This DNA exchange occurs via a process known as conjugation or horizontal transfer, which is a type of bacterial sexual reproduction in which two bacteria form an intimate bond and one transfers a package of DNA to the other. The DNA packets known as plasmids reside inside bacterial cells but multiply independently of the chromosomal DNA. A tiny number of their genes can code for specific tasks, like resistance to antimicrobial medications.
The most common mechanisms of horizontal transference in bacteria demand cell-cell interactions (conjugation). A protein known as relaxase must act in order to start the conjugative transfer. The recipient bacterium effectively inherits the donor bacterium’s DNA through replication (in the case of plasmids). If the genetic material gained through horizontal transference does not influence the recipient cells’ fitness (ability to leave offspring), horizontal transference may constitute an evolutionary success for those cells, aiding in adaptation and the colonization of new environments. Therefore, one of the most important projects in the global fight against bacteria that are resistant to antibiotics is knowing the nature of the processes that govern the transfer of plasmids and how it can be interrupted.
Figure 2. Bacterial conjugation, often known as bacterial sex, is a key method of horizontal gene transfer in which DNA is directly transferred from a donor bacterium to a receiver bacterium. In diagram 1- The donor cell produces pilus. 2- Pilus attaches to the recipient DNA is then transferred to the recipient cell. 4- Both cells circularize their plasmids, synthesize second strands, and reproduce pili; both cells are now viable donors.
Credits: By Adenosine from Creative Commons Attribution-Share Alike 3.0 Unported license
With the help of various disciplines such as microbiology, molecular biology, and chemistry, a group of researchers from the Department of Life Sciences and the MRC Centre for Molecular Bacteriology and Infections recently published in the prestigious journal Nature Microbiology one of the molecular mechanisms responsible for horizontal gene transfer processes. The researchers discovered that a protein from the donor bacteria called TraN functions as a “plug” to adhere to a certain outer membrane receptor, or “socket,” in the recipient bacterium during conjugation. Each of the four TraN protein variations that are expressed by plasmids that are exchanged through conjugation binds to a distinct outer membrane receptor in the recipient bacterium, allowing for effective plasmid transfer from one cell to another.
The group is still investigating the intricate relationships between TraN and receptors, including the mechanisms behind plasmid specialization and the dynamics and preferences of conjugation in mixed-microbe communities. They anticipate that this work will serve as a springboard for fresh strategies to stop the spread of antibiotic resistance. In the words of the investigation’s researchers “Understanding the mechanism by which bacteria pass on their capacity to withstand antibiotic treatment and ultimately stopping it will go a long way toward slowing the spread of resistance”. Therefore, in order to stop the emergence of antibiotic resistance in a range of laboratory and environmental conditions, it is important to find specialized conjugation inhibitors between TraN proteins and receptors. These findings open a new avenue in the search for new and more effective synthetic inhibitors that are promising prospects in the war against the spread of plasmids. Plants are an abundant source of bioactive substances like phenolics, which can alter bacterial resistance. Therefore, a contemporary strategy involves isolating compounds from various medicinal plants in order to find new inhibitors that prevented the conjugal transfer of plasmids.
- Mazel, D. & Davies, J. Antibiotic resistance in microbes. Cell. Mol. Life Sci. CMLS 56, 742–754 (1999).
- Tan, Y.-T., Tillett, D. J. & McKay, I. A. Molecular strategies for overcoming antibiotic resistance in bacteria. Mol. Med. Today 6, 309–314 (2000).
- Andersson, D. I. Persistence of antibiotic-resistant bacteria. Curr. Opin. Microbiol. 6, 452–456 (2003).
- Graf, F. E., Palm, M., Warringer, J. & Farewell, A. Inhibiting conjugation as a tool in the fight against antibiotic resistance. Drug Dev. Res. 80, 19–23 (2019).
- Low, W. W. et al. Mating pair stabilization mediates bacterial conjugation species specificity. Nat. Microbiol. 7, 1016–1027 (2022).