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Plasmid-mediated resistance

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81-570: Plasmid-mediated resistance is the transfer of antibiotic resistance genes which are carried on plasmids . Plasmids possess mechanisms that ensure their independent replication as well as those that regulate their replication number and guarantee stable inheritance during cell division. By the conjugation process, they can stimulate lateral transfer between bacteria from various genera and kingdoms. Numerous plasmids contain addiction-inducing systems that are typically based on toxin-antitoxin factors and capable of killing daughter cells that don't inherit

162-560: A broad variety of resistance genes. Members of family Enterobacteriaceae, for example, Escherichia coli or Klebsiella pneumoniae pose the biggest threat regarding plasmid-mediated resistance in hospital- and community-acquired infections. B-lactamases are antibiotic-hydrolyzing enzymes that typically cause resistance to b-lactam antibiotics. These enzymes are prevalent in Streptomyces, and together with related enzymes discovered in pathogenic and non-pathogenic bacteria, they form

243-628: A defense against drugs used to treat them, or certain strains of microbes that have a natural resistance to antimicrobials becoming much more prevalent than the ones that are easily defeated with medication. While antimicrobial resistance does occur naturally over time, the use of antimicrobial agents in a variety of settings both within the healthcare industry and outside of has led to antimicrobial resistance becoming increasingly more prevalent. Although many microbes develop resistance to antibiotics over time though natural mutation, overprescribing and inappropriate prescription of antibiotics have accelerated

324-517: A higher yield of crops has resulted in many of these microbes evolving a tolerance against these antimicrobial agents. Currently there are over 4000 antimicrobial pesticides registered with the US Environmental Protection Agency (EPA) and sold to market, showing the widespread use of these agents. It is estimated that for every single meal a person consumes, 0.3 g of pesticides is used, as 90% of all pesticide use

405-408: A limited amount of time or money to see a doctor. This increased access makes it extremely easy to obtain antimicrobials. An example is India, where in the state of Punjab 73% of the population resorted to treating their minor health issues and chronic illnesses through self-medication. Self-medication is higher outside the hospital environment, and this is linked to higher use of antibiotics, with

486-611: A major threat to public health." Each year, nearly 5 million deaths are associated with AMR globally. In 2019, global deaths attributable to AMR numbered 1.27 million in 2019. That same year, AMR may have contributed to 5 million deaths and one in five people who died due to AMR were children under five years old. In 2018, WHO considered antibiotic resistance to be one of the biggest threats to global health, food security and development. Deaths attributable to AMR vary by area: The European Centre for Disease Prevention and Control calculated that in 2015 there were 671,689 infections in

567-442: A microbe. All types of microbes can develop drug resistance. Thus, there are antibiotic, antifungal, antiviral and antiparasitic resistance. Antibiotic resistance is a subset of antimicrobial resistance. This more specific resistance is linked to bacteria and thus broken down into two further subsets, microbiological and clinical. Microbiological resistance is the most common and occurs from genes, mutated or inherited, that allow

648-487: A microbial community, it can then spread to other microbes in the community, potentially moving from a non-disease causing microbe to a disease-causing microbe. This process is heavily driven by the natural selection processes that happen during antibiotic use or misuse. Over time, most of the strains of bacteria and infections present will be the type resistant to the antimicrobial agent being used to treat them, making this agent now ineffective to defeat most microbes. With

729-403: A number of antibiotics used to treat a dysentery epidemic. Shigella is a genus of Gram-negative, aerobic, non-spore-forming, non-motile, rod-shaped bacteria. Resistance genes are ones that give rise to proteins that modify the antibiotic or pump it out. They are different from mutations that give bacteria resistance to antibiotics by preventing the antibiotic from getting in or changing the shape of

810-492: A number of resistance-related molecules, such as carbapenemases and ESBLs. Examples of resistance mechanisms include different Qnr proteins, aminoglycose acetyltransferase aac(6')-Ib-cr that is able to hydrolyze ciprofloxacin and norfloxacin , as well as efflux transporters OqxAB and QepA. xResistance to aminoglycosides in Gram-negative pathogens is primarily caused by enzymes that acetylate, adenylate, or phosphorylate

891-471: A pattern which may have worsened during the COVID-19 pandemic. Studies have shown that common misconceptions about the effectiveness and necessity of antibiotics to treat common mild illnesses contribute to their overuse. Important to the conversation of antibiotic use is the veterinary medical system . Veterinary oversight is required by law for all medically important antibiotics. Veterinarians use

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972-400: A population of bacteria . Also, R-factors can be taken up by "DNA pumps" in their membranes via transformation , or less commonly through viral mediated transduction , or via bacteriophage, although conjugation is the most common means of antibiotic resistance spread. They contain the gene called RTF (Resistance transfer factor). it is a family of Gram-negative rod-shaped (bacilli) bacteria,

1053-724: A reduction of the prevalence of antimicrobial resistance in humans. In the United States the Veterinary Feed Directive went into practice in 2017 dictating that All medically important antibiotics to be used in feed or water for food animal species require a veterinary feed directive (VFD) or a prescription. Most pesticides protect crops against insects and plants, but in some cases antimicrobial pesticides are used to protect against various microorganisms such as bacteria, viruses, fungi, algae, and protozoa. The overuse of many pesticides in an effort to have

1134-461: A screening of 3,537 articles published in Europe, Asia, and North America was done. Of the 55,225 total people surveyed in the articles, 70% had heard of antibiotic resistance previously, but 88% of those people thought it referred to some type of physical change in the human body. Clinical misuse by healthcare professionals is another contributor to increased antimicrobial resistance. Studies done in

1215-713: A significant AMR subset, enables bacteria to survive antibiotic treatment, complicating infection management and treatment options. Resistance arises through spontaneous mutation, horizontal gene transfer , and increased selective pressure from antibiotic overuse, both in medicine and agriculture, which accelerates resistance development. The burden of AMR is immense, with nearly 5 million annual deaths associated with resistant infections. Infections from AMR microbes are more challenging to treat and often require costly alternative therapies that may have more severe side effects. Preventive measures, such as using narrow-spectrum antibiotics and improving hygiene practices, aim to reduce

1296-556: A virus for example. Excessive antimicrobial use has become one of the top contributors to the evolution of antimicrobial resistance. Since the beginning of the antimicrobial era, antimicrobials have been used to treat a wide range of infectious diseases. Overuse of antimicrobials has become the primary cause of rising levels of antimicrobial resistance. The main problem is that doctors are willing to prescribe antimicrobials to ill-informed individuals who believe that antimicrobials can cure nearly all illnesses, including viral infections like

1377-401: A wide spectrum of beta-lactam antibiotics. ESBL enzymes can hydrolyze all beta-lactam antibiotics, including cephalosporins, except for the carpabepenems. The first clinically observed ESBL enzymes were mutated versions of the narrow spectrum beta-lactamases, like TEM and SHV. Other ESBL enzymes originate outside of family Enterobacteriaceae, but have been spreading as well. In addition, since

1458-411: Is a major weakness, as livestock accounts for around 73% of global sales of antimicrobial agents, including antibiotics , antivirals , and antiparasitics . Considering the complex interactions between humans, animals and the environment, it is also important to consider the environmental aspects and contributors to antimicrobial resistance. Although there are still some knowledge gaps in understanding

1539-426: Is a naturally occurring process. Antimicrobial resistance can evolve naturally due to continued exposure to antimicrobials. Natural selection means that organisms that are able to adapt to their environment, survive, and continue to produce offspring. As a result, the types of microorganisms that are able to survive over time with continued attack by certain antimicrobial agents will naturally become more prevalent in

1620-431: Is a potential metric for the rate of AMR in the environment. This surveillance also allows for further investigation into the transmission routs between different ecosystems and human populations (including domesticated animals and livestock).   Such information gathered from wild bird biomes, can help identify patterns of diseased transmission and better target interventions.  These targeted interventions can inform

1701-508: Is an online global map of antimicrobial resistance developed by HealthMap which displays aggregated data on antimicrobial resistance from publicly available and user submitted data. The website can display data for a 25 miles (40 km) radius from a location. Users may submit data from antibiograms for individual hospitals or laboratories. European data is from the EARS-Net (European Antimicrobial Resistance Surveillance Network), part of

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1782-448: Is bigger than the R determinant. An IS 1 element separates the RTF and R determinant on either side before they combine into a single unit.The IS 1 components simplify it for R determinants to be transferred between different R-RTF unit types. Bacteria containing F-factors (said to be "F+") have the capability for horizontal gene transfer ; they can construct a sex pilus , which emerges from

1863-546: Is illogical as antibiotics are used to treat infections and not prevent infections. 80% of antibiotic use in the U.S. is for agricultural purposes and about 70% of these are medically important. Overusing antibiotics gives the bacteria time to adapt leaving higher doses or even stronger antibiotics needed to combat the infection. Though antibiotics for growth promotion were banned throughout the EU in 2006, 40 countries worldwide still use antibiotics to promote growth. This can result in

1944-724: Is in agriculture. A majority of these products are used to help defend against the spread of infectious diseases, and hopefully protect public health. But out of the large amount of pesticides used, it is also estimated that less than 0.1% of those antimicrobial agents, actually reach their targets. That leaves over 99% of all pesticides used available to contaminate other resources. In soil, air, and water these antimicrobial agents are able to spread, coming in contact with more microorganisms and leading to these microbes evolving mechanisms to tolerate and further resist pesticides. The use of antifungal azole pesticides that drive environmental azole resistance have been linked to azole resistance cases in

2025-606: Is limited, the World Health Organization Advisory Group on Integrated Surveillance of Antimicrobial Resistance strongly recommended the reduction of use of medically important antimicrobials in livestock. Additionally, the Advisory Group stated that such antimicrobials should be expressly prohibited for both growth promotion and disease prevention in food producing animals. By mapping antimicrobial consumption in livestock globally, it

2106-435: Is scarce, but needed to support antibiotic stewardship in veterinary medicine. By comparison there is a lack of national and international monitoring programs for antifungal resistance. Antimicrobial stewardship programmes appear useful in reducing rates of antimicrobial resistance. The antimicrobial stewardship program will also provide pharmacists with the knowledge to educate patients that antibiotics will not work for

2187-516: Is through increased contact with densely populated areas, human waste, domestic animals, and domestic animal/livestock waste. Wild migrating birds interact with sedentary birds in different environments along their migration route.  This increases the rate and diversity of AMR across varying ecosystems. Neglect of wildlife in the global discussions surrounding health security and AMR, creates large barriers to true AMR surveillance. The surveillance of anti-microbial resistant organisms in wild birds

2268-415: The COVID-19 pandemic redirected resources and scientific attention away from AMR, intensifying the challenge. The WHO defines antimicrobial resistance as a microorganism's resistance to an antimicrobial drug that was once able to treat an infection by that microorganism. A person cannot become resistant to antibiotics. Resistance is a property of the microbe, not a person or other organism infected by

2349-531: The ECDC . ResistanceMap is a website by the Center for Disease Dynamics, Economics & Policy and provides data on antimicrobial resistance on a global level. The WHO's AMR global action plan also recommends antimicrobial resistance surveillance in animals. Initial steps in the EU for establishing the veterinary counterpart EARS-Vet (EARS-Net for veterinary medicine) have been made. AMR data from pets in particular

2430-687: The Pharmacokinetic /pharmacodynamic model (PK/PD) approach to ensuring that the correct dose of the drug is delivered to the correct place at the correct timing. Increased antibiotic use during the early waves of the COVID-19 pandemic may exacerbate this global health challenge . Moreover, pandemic burdens on some healthcare systems may contribute to antibiotic-resistant infections. On the other hand, "increased hand hygiene, decreased international travel, and decreased elective hospital procedures may have reduced AMR pathogen selection and spread in

2511-520: The 30 most common infections in adults and children to reduce inappropriate prescribing in primary care and hospitals. Narrow-spectrum antibiotics are preferred due to their lower resistance potential, and broad-spectrum antibiotics are only recommended for people with more severe symptoms. Some antibiotics are more likely to confer resistance, so are kept as reserve antibiotics in the AWaRe book. Various diagnostic strategies have been employed to prevent

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2592-448: The AMR umbrella, posing significant challenges to healthcare worldwide. Misuse and improper management of antimicrobials are primary drivers of this resistance, though it can also occur naturally through genetic mutations and the spread of resistant genes. Microbes resistant to multiple drugs are termed multidrug-resistant (MDR) and are sometimes called superbugs . Antibiotic resistance,

2673-409: The EU and European Economic Area caused by antibiotic-resistant bacteria, resulting in 33,110 deaths. Most were acquired in healthcare settings. In 2019 there were 133,000 deaths caused by AMR. AMR is driven largely by the misuse and overuse of antimicrobials. Yet, at the same time, many people around the world do not have access to essential antimicrobials. This leads to microbes either evolving

2754-466: The R-RTF (Resistance Transfer Factor) molecules are found in the resistance plasmid, which can be conceptualized as a circular piece of DNA with a length of 80 to 95 kb. This plasmid shares many genes with the F factor and is largely homologous to it. Additionally, it has a fin 0 gene that inhibits the transfer operon's functionality. The size and number of drug resistance genes in each R factor varies.The RTF

2835-848: The UK," highlights the urgency of reevaluating antibiotic treatment durations amidst the global challenge of antimicrobial resistance (AMR). It investigates the effectiveness of shorter versus longer antibiotic regimens for respiratory tract infections (RTIs) in a UK secondary care setting, emphasizing the need for evidence-based prescribing practices to optimize patient outcomes and combat AMR. There are multiple national and international monitoring programs for drug-resistant threats, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant S. aureus (VRSA), extended spectrum beta-lactamase (ESBL) producing Enterobacterales , vancomycin-resistant Enterococcus (VRE), and multidrug-resistant Acinetobacter baumannii (MRAB). ResistanceOpen

2916-590: The US show that the indication for treatment of antibiotics, choice of the agent used, and the duration of therapy was incorrect in up to 50% of the cases studied. In 2010 and 2011 about a third of antibiotic prescriptions in outpatient settings in the United States were not necessary. Another study in an intensive care unit in a major hospital in France has shown that 30% to 60% of prescribed antibiotics were unnecessary. These inappropriate uses of antimicrobial agents promote

2997-503: The aggressive prescription of antibiotics as necessary to avoid failing to provide adequate care. This demonstrates how a majority of doctors underestimate the impact that their own prescribing habits have on antimicrobial resistance as a whole. It also confirms that some physicians may be overly cautious and prescribe antibiotics for both medical or legal reasons, even when clinical indications for use of these medications are not always confirmed. This can lead to unnecessary antimicrobial use,

3078-515: The amount of anti-microbial resistance (AMR) to the bird population.  The introduction of AMR to wild birds positively correlates with human pollution and increased human contact.  Additionally, wild birds can participate in horizontal gene transfer with bacteria, leading to the transmission of antibiotic-resistant genes (ARG). For simplicity, wild bird populations can be divided into two major categories, wild sedentary birds and wild migrating birds.  Wild sedentary bird exposure to AMR

3159-492: The bacteria to resist the mechanism to kill the microbe associated with certain antibiotics. Clinical resistance is shown through the failure of many therapeutic techniques where the bacteria that are normally susceptible to a treatment become resistant after surviving the outcome of the treatment. In both cases of acquired resistance, the bacteria can pass the genetic catalyst for resistance through horizontal gene transfer: conjugation, transduction , or transformation . This allows

3240-443: The chances of members of the population acquiring a mutation that increases resistance. Many individuals stop taking antibiotics when they begin to feel better. When this occurs, it is possible that the microbes that are less susceptible to treatment still remain in the body. If these microbes are able to continue to reproduce, this can lead to an infection by bacteria that are less susceptible or even resistant to an antibiotic. AMR

3321-518: The clinical setting. The same issues confront the novel antifungal classes (e.g. orotomides ) which are again being used in both the clinic and agriculture. Wildlife, including wild and migratory birds , serve as a reservoir for zoonotic disease and antimicrobial-resistant organisms.  Birds are a key link between the transmission of zoonotic diseases to human populations.  By the same token, increased contact between wild birds and human populations (including domesticated animals), has increased

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3402-401: The common cold. In an analysis of drug prescriptions, 36% of individuals with a cold or an upper respiratory infection (both usually viral in origin) were given prescriptions for antibiotics. These prescriptions accomplished nothing other than increasing the risk of further evolution of antibiotic resistant bacteria. Using antimicrobials without prescription is another driving force leading to

3483-466: The considerable size of DNA required to encode the conjugation mechanisms that allow for cell-to-cell conjugation. R-factors are also called a resistance factors or resistance plasmid. They are tiny, circular DNA elements that are self-replicating, that contain antibiotic resistance genes. They were first found in Japan in 1959 when it was discovered that some Shigella strains had developed resistance to

3564-427: The contemporary bacteria from the active layer of thawed ground above them, which may mean that this risk is "no greater" than from any other soil. There have been increasing public calls for global collective action to address the threat, including a proposal for an international treaty on antimicrobial resistance. Further detail and attention is still needed in order to recognize and measure trends in resistance on

3645-492: The development of resistance. Stewardship interventions may reduce the length of stay by an average of slightly over 1 day while not increasing the risk of death. Dispensing, to discharged in-house patients, the exact number of antibiotic pharmaceutical units necessary to complete an ongoing treatment can reduce antibiotic leftovers within the community as community pharmacies can have antibiotic package inefficiencies. Plasmid Too Many Requests If you report this error to

3726-526: The donor bacterium and ensnares the recipient bacterium, draws it in, and eventually triggers the formation of a mating bridge, merging the cytoplasms of two bacteria via a controlled pore. This pore allows the transfer of genetic material, such as a plasmid . Conjugation allows two bacteria , not necessarily from the same species , to transfer genetic material one way. Since many R-factors contain F-plasmids, antibiotic resistance can be easily spread among

3807-494: The environment, and those without this resistance will become obsolete. Some contemporary antimicrobial resistances have also evolved naturally before the use of antimicrobials of human clinical uses. For instance, methicillin -resistance evolved as a pathogen of hedgehogs , possibly as a co-evolutionary adaptation of the pathogen to hedgehogs that are infected by a dermatophyte that naturally produces antibiotics. Also, many soil fungi and bacteria are natural competitors and

3888-399: The evolution of antimicrobial resistance by supporting the bacteria in developing genetic alterations that lead to resistance. According to research conducted in the US that aimed to evaluate physicians' attitudes and knowledge on antimicrobial resistance in ambulatory settings, only 63% of those surveyed reported antibiotic resistance as a problem in their local practices, while 23% reported

3969-487: The food industry, specifically with food producing animals. With an ever-increasing human population, there is constant pressure to intensify productivity in many agricultural sectors, including the production of meat as a source of protein. Antibiotics are fed to livestock to act as growth supplements, and a preventive measure to decrease the likelihood of infections. Farmers typically use antibiotics in animal feed to improve growth rates and prevent infections. However, this

4050-466: The genes encoding virulence determinants, specific enzymes or resistance to toxic heavy metals . Multiple resistance genes are commonly arranged in the resistance cassettes. The antibiotic resistance genes found on the plasmids confer resistance to most of the antibiotic classes used nowadays, for example, beta-lactams , fluoroquinolones and aminoglycosides . It is very common for the resistance genes or entire resistance cassettes to be re-arranged on

4131-718: The inability of known causative agents of contagious diseases to survive being frozen and thawed makes this threat unlikely. Instead, there have been suggestions that when modern pathogenic bacteria interact with the ancient ones, they may, through horizontal gene transfer , pick up genetic sequences which are associated with antimicrobial resistance, exacerbating an already difficult issue. Antibiotics to which permafrost bacteria have displayed at least some resistance include chloramphenicol , streptomycin , kanamycin , gentamicin , tetracycline , spectinomycin and neomycin . However, other studies show that resistance levels in ancient bacteria to modern antibiotics remain lower than in

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4212-416: The increased use of antimicrobial agents, there is a speeding up of this natural process. In the vast majority of countries, antibiotics can only be prescribed by a doctor and supplied by a pharmacy. Self-medication by consumers is defined as "the taking of medicines on one's own initiative or on another person's suggestion, who is not a certified medical professional", and it has been identified as one of

4293-454: The infection and other health problems a person may have. For many infections once a person has improved there is little evidence that stopping treatment causes more resistance. Some, therefore, feel that stopping early may be reasonable in some cases. Other infections, however, do require long courses regardless of whether a person feels better. Delaying antibiotics for ailments such as a sore throat and otitis media may have not different in

4374-501: The international level; the idea of a global tracking system has been suggested but implementation has yet to occur. A system of this nature would provide insight to areas of high resistance as well as information necessary for evaluating programs, introducing interventions and other changes made to fight or reverse antibiotic resistance. Delaying or minimizing the use of antibiotics for certain conditions may help safely reduce their use. Antimicrobial treatment duration should be based on

4455-401: The lack of knowledge of the public on, firstly, the dangerous effects of certain antimicrobials (for example ciprofloxacin which can cause tendonitis , tendon rupture and aortic dissection ) and, secondly, broad microbial resistance and when to seek medical care if the infection is not clearing. In order to determine the public's knowledge and preconceived notions on antibiotic resistance,

4536-419: The majority of antibiotics being used in the community rather than hospitals. The prevalence of self-medication in low- and middle-income countries (LMICs) ranges from 8.1% to 93%. Accessibility, affordability, and conditions of health facilities, as well as the health-seeking behavior, are factors that influence self-medication in low- and middle-income countries. Two significant issues with self-medication are

4617-400: The mechanisms and transmission pathways, environmental pollution is considered a significant contributor to antimicrobial resistance. Important contributing factors are through "antibiotic residues", "industrial effluents", " agricultural runoffs ", "heavy metals", " biocides and pesticides " and "sewage and wastewater" that create reservoirs for resistant genes and bacteria that facilitates

4698-459: The medication. On mobile elements, such as plasmids, are the genes that encode these enzymes. Aminoglycoside resistance genes are also commonly found together with ESBL genes. Resistance to aminoglycosides is conferred via numerous aminoglycoside-modifying enzymes and 16S rRNA methyltransferases. Resistance to aminoglycosides is conferred via numerous mechanisms: Study investigating physiological effect of pHK01 plasmid in host E.coli J53 found that

4779-400: The next six years. In their first major declaration on the issue since 2016, global leaders also committed to raising $ 100 million to update and implement AMR action plans. However, the final draft of the declaration omitted an earlier target to reduce antibiotic use in animals by 30% by 2030, due to opposition from meat-producing countries and the farming industry. Critics argue this omission

4860-444: The original antibiotic penicillin discovered by Alexander Fleming rapidly lost clinical effectiveness in treating humans and, furthermore, none of the other natural penicillins (F, K, N, X, O, U1 or U6) are currently in clinical use. Antimicrobial resistance can be acquired from other microbes through swapping genes in a process termed horizontal gene transfer . This means that once a gene for resistance to an antibiotic appears in

4941-506: The overuse of antibiotics to self-treat diseases like the common cold, cough, fever, and dysentery resulting in an epidemic of antibiotic resistance in countries like Bangladesh, risking its spread around the globe. Introducing strict antibiotic stewardship in the outpatient setting to reduce inappropriate prescribing of antibiotics may reduce the emerging bacterial resistance. The WHO AWaRe (Access, Watch, Reserve) guidance and antibiotic book has been introduced to guide antibiotic choice for

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5022-426: The overuse of antifungal therapy in the clinic, proving a safe alternative to empirical antifungal therapy, and thus underpinning antifungal stewardship schemes. Antimicrobial stewardship teams in hospitals are encouraging optimal use of antimicrobials. The goals of antimicrobial stewardship are to help practitioners pick the right drug at the right dose and duration of therapy while preventing misuse and minimizing

5103-459: The pathogenic bacteria that are most frequently found in the environment and clinical cases, as a result, they are significantly impacted by the use of antibiotics in agriculture, the ecosystem, or the treatment of diseases. In Enterobacteriaceae, 28 different plasmid types can be identified by PCR-based replicon typing (PBRT).The plasmids that have been frequently reported [IncF, IncI, IncA/C, IncL (previously designated IncL/M), IncN, and IncH] contain

5184-450: The permafrost, and it is possible for microorganisms to resume their life functions once it thaws. While some common pathogens such as influenza , smallpox or the bacteria associated with pneumonia have failed to survive intentional attempts to revive them, more cold-adapted microorganisms such as anthrax , or several ancient plant and amoeba viruses, have successfully survived prolonged thaw. Some scientists have argued that

5265-621: The plasmid during cell division. Plasmids often carry multiple antibiotic resistance genes, contributing to the spread of multidrug-resistance (MDR). Antibiotic resistance mediated by MDR plasmids severely limits the treatment options for the infections caused by Gram-negative bacteria , especially family Enterobacteriaceae . The global spread of MDR plasmids has been enhanced by selective pressure from antimicrobial medications used in medical facilities and when raising animals for food. Resistance plasmids by definition carry one or more antibiotic resistance genes. They are frequently accompanied by

5346-913: The plasmid reduced bacterial motility and conferred resistance to beta-lactams. The pHK01 produced plasmid-encoded small RNAs and mediated expression of host sRNAs. These sRNAs were antisense to genes involved in replication, conjugate transfer and plasmid stabilisation : AS-repA3 (CopA) , AS-traI, AS-finO, AS-traG, AS-pc02 . The over-expression of one of the plasmid-encoded antisense sRNAs : AS-traI shortened t la log phase of host growth. Antibiotic resistance Antimicrobial resistance ( AMR or AR ) occurs when microbes evolve mechanisms that protect them from antimicrobials , which are drugs used to treat infections. This resistance affects all classes of microbes, including bacteria ( antibiotic resistance), viruses ( antiviral resistance), protozoa ( antiprotozoal resistance), and fungi ( antifungal resistance). Together, these adaptations fall under

5427-732: The plasmids that carry ESBL genes also commonly encode resistance determinants for many other antibiotics, ESBL strains are often resistant to many non-beta-lactam antibiotics as well, leaving very few options for the treatment. Carbapenemases represent type of ESBL which are able to hydrolyze carbapenem antibiotics that are considered as the last-resort treatment for ESBL-producing bacteria. KPC, NDM-1, VIM and OXA-48 carbapenemases have been increasingly reported worldwide as causes of hospital-acquired infections . Several studies have shown that fluoroquinolone resistance has enhanced worldwide, especially in Enterobacteriaceae members. QnrA

5508-406: The primary reasons for the evolution of antimicrobial resistance. Self-medication with antibiotics is an unsuitable way of using them but a common practice in resource-constrained countries. The practice exposes individuals to the risk of bacteria that have developed antimicrobial resistance. Many people resort to this out of necessity, when access to a physician is unavailable, or when patients have

5589-488: The problem. It is possible that as many as 1 in 3 prescriptions written for antibiotics are unnecessary. Every year, approximately 154 million prescriptions for antibiotics are written. Of these, up to 46 million are unnecessary or inappropriate for the condition that the patient has. Microbes may naturally develop resistance through genetic mutations that occur during cell division, and although random mutations are rare, many microbes reproduce frequently and rapidly, increasing

5670-486: The protein family known as the "b-lactamase superfamily". it is hypothesized that b-lactamases also serve a double purpose, such as housekeeping and antibiotic resistance. Both narrow spectrum beta-lactamases (e.g. penicillinases) and extended spectrum beta-lactamases (ESBL) are common for resistance plasmids in Enterobacteriaceae . Often multiple beta-lactamase genes are found on the same plasmid hydrolyzing

5751-410: The rate of complications compared with immediate antibiotics, for example. When treating respiratory tract infections , clinical judgement is required as to the appropriate treatment (delayed or immediate antibiotic use). The study, "Shorter and Longer Antibiotic Durations for Respiratory Infections: To Fight Antimicrobial Resistance—A Retrospective Cross-Sectional Study in a Secondary Care Setting in

5832-449: The resistance to spread across the same species of pathogen or even similar bacterial pathogens. WHO report released April 2014 stated, "this serious threat is no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone, of any age, in any country. Antibiotic resistance—when bacteria change so antibiotics no longer work in people who need them to treat infections—is now

5913-551: The same plasmid or be moved to a different plasmid or chromosome by means of recombination systems. Examples of such systems include integrons , transposons , and IS CR -promoted gene mobilization. Most of the resistance plasmids are conjugative, meaning that they encode all the needed components for the transfer of the plasmid to another bacterium, and that isn't present in mobilizable plasmids. According to that, Mobilizable plasmids are smaller in size (usually < 10 kb) while conjugative plasmids are larger (usually > 30 kb) due to

5994-419: The short term" during the COVID-19 pandemic. The use of disinfectants such as alcohol-based hand sanitizers, and antiseptic hand wash may also have the potential to increase antimicrobial resistance. Extensive use of disinfectants can lead to mutations that induce antimicrobial resistance. A 2024 United Nations High-Level Meeting on AMR has pledged to reduce deaths associated with bacterial AMR by 10% over

6075-654: The spread of resistance. The WHO claims that AMR is one of the top global public health and development threats, estimating that bacterial AMR was directly responsible for 1.27 million global deaths in 2019 and contributed to 4.95 million deaths . Moreover, the WHO and other international bodies warn that AMR could lead to up to 10 million deaths annually by 2050 unless actions are taken. Global initiatives, such as calls for international AMR treaties, emphasize coordinated efforts to limit misuse, fund research, and provide access to necessary antimicrobials in developing nations. However,

6156-470: The target protein. R-factors have been known to contain up to ten resistance genes. They can also spread easily as they contain genes for constructing pili, which allow them to transfer the R-factor to other bacteria. R-factors have contributed to the growing antibiotic resistance crisis because they quickly spread resistance genes among bacteria. The R factor by itself cannot be transmitted. The majority of

6237-814: The transfer of human pathogens. Unused or expired antibiotics, if not disposed of properly, can enter water systems and soil. Discharge from pharmaceutical manufacturing and other industrial companies can also introduce antibiotics and other chemicals into the environment. These factors allow for creating selective pressure for resistant bacteria. Antibiotics used in livestock and aquaculture can contaminate soil and water, which promotes resistance in environmental microbes. Heavy metals such as zinc , copper and mercury , and also biocides and pesticides, can co- select for antibiotic resistance, enhancing their speed. Inadequate treatment of sewage and wastewater allows resistant bacteria and genes to spread through water systems. The antimicrobial resistance crisis also extends to

6318-413: The transfer of resistant bacterial strains into the food that humans eat, causing potentially fatal transfer of disease. While the practice of using antibiotics as growth promoters does result in better yields and meat products, it is a major issue and needs to be decreased in order to prevent antimicrobial resistance. Though the evidence linking antimicrobial usage in livestock to antimicrobial resistance

6399-404: The use of antimicrobial agents and reduce the persistence of multi-drug resistant organisms. Permafrost is a term used to refer to any ground that remained frozen for two years or more, with the oldest known examples continuously frozen for around 700,000 years. In the recent decades, permafrost has been rapidly thawing due to climate change . The cold preserves any organic matter inside

6480-409: Was predicted that in 228 countries there would be a total 67% increase in consumption of antibiotics by livestock by 2030. In some countries such as Brazil, Russia, India, China, and South Africa it is predicted that a 99% increase will occur. Several countries have restricted the use of antibiotics in livestock, including Canada, China, Japan, and the US. These restrictions are sometimes associated with

6561-541: Was the first known plasmid-mediated gene associated in quinolone resistance. Quinolone resistance genes are frequently located on the same plasmid as the ESBL genes. The proteins known as QnrS, QnrB, QnrC, and QnrD are four others that are similar. Numerous variants have been found for qnrA, qnrS, and qnrB, and they are distinguished by sequential numbers. The qnr genes can be discovered in integrons and transposons on MDR plasmids of various incompatibility groups, which could carry

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