Last week (18 – 24 November) marked World Antimicrobial Resistance (AMR) Awareness Week (WAAW), a WHO-led initiative to improve understanding of antimicrobial resistance and promote best practices that help prevent the further emergence and spread of resistant infections.
The WHO theme for 2025 is “Act Now: Protect Our Present, Secure Our Future,” emphasising the urgent need for coordinated, cross-sector action as AMR continues to impact health systems, food production, the environment, and global economies.
According to World Health Organization (WHO) report of 2019, AMR is responsible for the deaths of 700,000 people, while it’s estimated that by 2050 the figure will have risen to 20 million, costing over $ 2.9 trillion [4]. As a result, it has become a major problem, posing a serious danger to our lives and economy
What is AMR: Antimicrobial resistance (AMR) refers to the survivability of pathogens against the exposure and administration of antibiotics that could kill them or restrict their proliferation. This happens when parasite change or adopt over time, making the medicine used against them less effective or completely ineffective, as a result infections become harder to treat, leading to increased risk of disease spread widely. Antimicrobial resistance has become major global health concern due to the misuse and overuse of antibiotics. The Gram-positive and Gram-negative bacteria-related infections became difficult to treat due to multidrug resistance, and could not be treated with traditional antibiotics. In both pre-antibiotic and antibiotic periods, antibiotic resistance has badly affected antibiotic efficacy in clinical practices
Despite mounting attention in recent years, the health threats posed by antimicrobial resistance are not new. Antimicrobial resistance has dogged infectious disease treatment processes since the first modern antimicrobials were discovered. In fact, resistance began to appear soon after the introduction of early antibiotics such as penicillin, with some bacteria developing mechanisms to evade their effects within only a few years. Over time, the widespread and sometimes inappropriate use of antimicrobials in human medicine, agriculture, and animal husbandry has accelerated the evolution and spread of resistant strains. Today, antimicrobial resistance is recognized as a global health crisis, undermining our ability to treat common infections, increasing healthcare costs, and threatening medical procedures that rely on effective antibiotics, such as surgeries, cancer chemotherapy, and organ transplants.
Mechanism of Antimicrobial Resistance (How do organisms make antibiotics less effective or ineffective):
Before we understand the mechanism of Antimicrobial Resistance by pathogens it is important first to understand the mechanism of antibiotics which are used to treat microbial infections. The antibiotics mainly attack the biochemistry and physiology of the microbial cells to reduce their growth or cause death. Some antibiotics destroy the cell walls or cell membranes of bacterial cells by dissolving the β-lactam and glycopeptide components, while other antibiotics target the protein synthetic machinery by linking with ribosomal units, which stops the antibacterial activity of those microbes These cell-wall-targeting antibiotics include aminoglycosides, tetracycline, linezolid, chloramphenicol, and macrolides. The other cell-machinery-targeting antibiotics and nucleic acid synthesis interfering molecules include rifampin and fluoroquinolones (FQ). The remaining antibiotics are those that interfere with metabolic pathways and destroy the membrane matrix, including folic acid analogs, daptomycin, polymyxins, and sulphonamides.
Now understanding how bacteria deceive the above antibiotics mechanism and make them ineffective against them. There are two ways by which pathogens can counter back the medicine (antibiotics) one known as inherent AMR and another acquired AMR.
Inherent AMR refers to the resistance of pathogens due to its naturally existing structural and functional characteristics. This type of resistance is not acquired by the mutations or gene tranfer, as of mycoplasma's resistance to penicillin.
Acquired Resistance is due to the change in the genome (Mutations) of bacteria that converts it from one that is sensitive to antibiotic to one that is now resistant.
Pathogens can use multiple ways to make antibiotics
Altering Target sites of Antibody: This occurs by mutating a gene that functions in the synthesis of the target or by acquiring by HGT a gene that either encodes an alternative version of the target or encodes an enzyme that modifies the target. This resistance mechanism is possible because each chemotherapeutic agent acts on a specific target enzyme or cellular structure. e.g. resistance to vancomycin arises when bacteria “pick up” the vanA gene that encodes a protein that changes the terminal d-alanine in the pentapeptide of peptidoglycan to either d-lactate or d-serine. The affinity of ribosomes for erythromycin and chloramphenicol can be decreased by mutating the 23S rRNA to which they bind. Antimetabolite action may be resisted through alteration of susceptible enzymes. For example, in sulphonamide-resistant bacteria, the enzyme that uses p-aminobenzoic acid during folic acid synthesis often has a much lower affinity for sulphonamides
Drug Inactivation or Drug Degradation: A well-characterized mechanism of antimicrobial resistance is the enzymatic hydrolysis of the β-lactam ring in penicillin by penicillinase and other β-lactamases, rendering the drug incapable of binding its target PBPs.
Antibiotics may also undergo enzymatic inactivation via covalent modification. Like chloramphenicol is neutralized through acetylation, in which chloramphenicol acetyltransferase (CAT) transfers an acetyl group from acetyl-CoA to either of the drug’s hydroxyl moieties.
Similarly, aminoglycosides are inactivated through a diverse set of modifying enzymes, including: Aminoglycoside acetyltransferases (AACs) that acetylate amino groups, Aminoglycoside phosphotransferases (APHs) that phosphorylate hydroxyl groups, and Aminoglycoside nucleotidyltransferases (ANTs) that adenylylate hydroxyl groups.
Drug alteration: This resistance strategy of pathogens minimises the concentration of the antibiotic in the cell. This can be accomplished by altering membrane structure. In Gram-negative bacteria in particular, this is often achieved by modifying the structure or permeability of the outer membrane, which normally acts as a selective barrier. By altering porin proteins or reducing the number of poring, the bacteria allow fewer antibiotic molecules to diffuse into the cell. As a result, the effective intracellular concentration of the antibiotic remains too low to be harmful.
Drug extruding by efflux pumps: This approach is to pump the drug out of the cell after it has entered, using translocate, often called efflux pumps, that expel drugs. Efflux pumps are relatively nonspecific and pump many different drugs; therefore, they often confer multidrug resistance. Many efflux pumps are drug/proton ant porters that is, protons enter the cell as the drug leaves.
Horizontal gene transfer: The lateral gene transfer or horizontal gene transfer (HGT) contributes to the transfer of resistivity, its evolution, and maintenance among pathogenic bacteria and also plays a role in the destruction of antibiotic resistance genes (ARGs) transferred from the natural environment in clinical settings . The best example of HGT is the spread of carbapenem resistance in Enterobacteriaceae. The blaNDM-1 gene, which encodes a carbapenemase enzyme that breaks down carbapenem antibiotics, can spread rapidly through horizontal gene transfer. This gene has been found in various Enterobacteriaceae species, allowing them to resist the effects of carbapenem antibiotics. The spread of this gene among different bacterial species contributes to the widespread resistance to these last-resort antibiotics. An additional instance of horizontal gene transfer (HGT) is evident in the Shigella outbreak within the United Kingdom, resulting from the transfer of a plasmid-borne antibiotic resistance gene [48]. This dissemination of a plasmid carrying resistance to azithromycin enabled the proliferation of pathogens that were once infrequent, due to the decreased effectiveness of conventional antibiotics. In the end, several outbreaks involving distinct strains emerged as a consequence of these strains independently acquiring the same plasmid
Conjugation: . Conjugation is the mechanism by which DNA is transferred from cell to cell via cell surface pili or adhesions. It is aided by conjugative machinery, which is encoded by genes on autonomously replicating plasmids or integrative conjugative elements in the chromosome. The challenges of antibiotic resistance (AR) in hospital settings are further complicated by horizontal gene transfer (HGT), and this is prominently illustrated in the context of plasmid-mediated resistance to β-lactam antibiotics. Resistance mechanisms involving extended-spectrum β-lactamases (ESBLs) and carbapenemase, for instance, operate by breaking down β-lactam antibiotics like penicillin, carbapenems, and cephalosporins [50]. Notably, β-lactam resistance genes are frequently situated on plasmids, leading to their dissemination through conjugation within and between different species, particularly within the Enterobacteriaceae, Pseudomonas, and Acinetobacter families.

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