Mechanisms of Antibiotic Resistance: Understanding the Molecular and Genetic Basis of Bacterial Resistance

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Iheakolam Uchenna Caleb¹ , Moses Adondua Abah^2,3 , Micheal Abimbola Oladosu^3,4 , Micah Nnabuko Okwah^5,6 , Nathan Rimamsanati Yohanna^2,3 , Abah Sarah Onyeoche⁷ , Emmanuel Godwin Ogunjobi⁸ , Ebenezer Morayo Ale² , Ismaila Emmanuel Oluwasegun⁹ , Ejim Thomas Ejim¹⁰ , Amarachukwu Bernaldine Isiaka ¹¹

¹Department of Microbiology, Faculty of Biological and Physical Sciences, Abia State University, Uturu, Abia State, Nigeria

²Department of Biochemistry, Faculty of Biosciences, Federal University Wukari, Taraba State, Nigeria

³ResearchHub Nexus Institute, Nigeria

⁴Department of Biochemistry, Faculty of Basic Medical Sciences, University of Lagos, Lagos State, Nigeria

⁵Department of Internal Medicine, Cardiology Unit, Lagos University Teaching Hospital, Lagos State, Nigeria

⁶Department of Chronic Disease Epidemiology, Yale University, Connecticut, United States

⁷Department of Nursing, College of Health Sciences, Benue State University, Makurdi, Nigeria

⁸Department of Microbiology, Faculty of Science, Adekunle Ajasin University, Akungba-Akoko, Ondo state, Nigeria.

⁹Project Center for Agro Technologies, Skolkovo Institute of Science and Technology, Moscow, Russian Federation

¹⁰Department of Surgery, Faculty of Clinical Sciences, University College Hospital, Ibadan, Oyo State, Nigeria

¹¹School of Public Health, University of Port Harcourt, Rivers State, Nigeria

Corresponding Author Email: m.abah@fuwukari.edu.ng

DOI : https://doi.org/10.51470/APR.2025.04.02.51

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Introduction

Antibiotics have revolutionised the treatment of infectious diseases and dramatically decreased morbidity and mortality globally, making them one of the most revolutionary discoveries in contemporary medicine [1]. Antibiotics have made it possible to treat once-fatal bacterial infections, made complicated surgical procedures easier, and helped immunocompromised patients receiving chemotherapy or organ transplants since the discovery of penicillin in the early 20th century [2]. In addition to saving many lives, their widespread usage has improved worldwide public health and increased life expectancy. However, the unrelenting rise of antibiotic resistance has threatened to undo decades of medical advancement, undermining the astonishing effectiveness of antibiotics. The table below gives an overview of the major antibiotics, resistant pathogens and resistance patterns of the underpinned resistant organisms [3].

Antimicrobial resistance (AMR) has a startling global burden. According to recent systematic estimates, AMR was linked to around 5 million deaths globally and directly caused about 1.27 million deaths in 2019 alone [4]. The financial ramifications of resistant infections, which result in longer hospital stays, higher medical expenses, and lost productivity, exacerbate the clinical burden. AMR has been ranked as one of the top ten worldwide public health hazards by the World Health Organisation (WHO), highlighting its potential to undermine the effectiveness of critical medical interventions and destabilise health systems [5]. Due to restricted availability of new medications and diagnostic resources, the impact is especially acute in low- and middle-income nations [6].

Knowing the molecular and genetic mechanisms of resistance is essential, given the scope of the crisis. Bacteria use a variety of tactics to avoid the effects of antibiotics, such as biofilm formation, enzymatic drug degradation, target site modification, and efflux pump activation [7, 8]. Resistance determinants are frequently encoded on integrons, transposons, and plasmids at the genetic level, which speeds up the spread of resistance traits and allows horizontal gene transfer between species [9]. The intricacy of resistance evolution is highlighted by the interaction between molecular mechanisms and genetic mobility, underscoring the necessity of integrated surveillance and intervention strategies.

There are still gaps in our understanding despite advances in molecular microbiology and genomics. Especially in environments with limited resources, surveillance systems frequently fall short of capturing the entire range of resistance determinants. Moreover, few new antibiotics have been used in clinical settings in recent decades due to weak drug development pipelines [10]. The development of long-lasting treatment approaches is hampered by the absence of predictive models for resistance emergence and the incomplete knowledge of bacterial adaptive responses. A multidisciplinary strategy that integrates clinical epidemiology, public health policy, and molecular insights is needed to close these gaps.

This study has two goals and objectives. With a focus on the variety of tactics used by pathogens to avoid antimicrobial action, it first aims to critically explain the molecular, genetic, and biochemical mechanisms underpinning bacterial resistance. Second, it seeks to draw attention to the clinical implications of these mechanisms and investigate potential therapeutic approaches, such as the creation of new drugs, alternative treatments, and enhanced surveillance systems. This review aims to provide a thorough understanding of antibiotic resistance and guide strategies to lessen its worldwide impact by bridging molecular biology with clinical practice.

Literature review

Classification of Antibiotic Resistance

The complex phenomenon of antibiotic resistance is influenced by clinical procedures, environmental factors, and microbial genetics. Developing focused interventions and directing therapeutic choices requires an understanding of their classification. In general, resistance mechanisms can be divided into three categories: intrinsic versus acquired, phenotypic versus genotypic, and cross-resistance versus multidrug resistance. Each of these categories has unique treatment and surveillance implications.

Intrinsic vs Acquired Resistance

The natural, innate insensitivity of some bacterial species to particular antibiotics is known as intrinsic resistance. This resistance is not caused by previous exposure to antibiotics; rather, it is encoded in the bacterial genome. For instance, Pseudomonas aeruginosa’s low outer membrane permeability and efflux systems make it inherently resistant to many β-lactams [11]. Similarly, due to the lack of target penicillin-binding proteins, Enterococcus species show intrinsic resistance to cephalosporins [12].

On the other hand, acquired resistance results from horizontal gene transfer or genetic mutations, which are frequently brought on by exposure to antibiotics. Because it can spread quickly among bacterial populations, this type of resistance is more dynamic and clinically concerning. Carbapenemase genes in Klebsiella pneumoniae and plasmid-mediated β-lactamase production in Escherichia coli are examples of mechanisms 13]. Multidrug-resistant (MDR) infections are primarily caused by acquired resistance, which presents serious problems for public health [14].

Phenotypic vs Genotypic Resistance

When bacteria with no known genetic resistance markers survive exposure to antibiotics, this is known as phenotypic resistance. Transient physiological conditions like biofilm formation, changed metabolic activity, or stress-induced tolerance can cause this [15]. For example, biofilm-forming Staphylococcus aureus may be less susceptible to vancomycin if it does not carry van genes. Conversely, genotypic resistance is characterised by the existence of particular resistance genes or mutations that can be identified using molecular diagnostics. Examples include the rpoB mutations that confer rifampicin resistance in Mycobacterium tuberculosis and the mecA gene in methicillin-resistant Staphylococcus aureus (MRSA) [16]. Due to compensatory mechanisms or variability in gene expression, genotypic methods may not always correlate with phenotypic outcomes, despite providing quick and accurate detection [17].

Cross-Resistance and Multidrug Resistance

When a single resistance mechanism provides defence against several antibiotics, frequently from the same class, this is known as cross-resistance. For instance, fluoroquinolones and chloramphenicol can be expelled by efflux pumps such as AcrAB-TolC in E. coli [18]. This phenomenon calls for cautious antibiotic stewardship and complicates empirical therapy. Resistance to three or more antimicrobial classes is known as multidrug resistance (MDR), which is often caused by cumulative genetic events. Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa are examples of multidrug-resistant (MDR) pathogens that are well-known for their tenacity and correlation with nosocomial infections [19]. MDR mechanisms, which are frequently encoded on mobile genetic elements that enable quick dissemination, include enzymatic degradation, target modification, and membrane impermeability [20].

Molecular Mechanisms of Antibiotic Resistance

Bacteria use a wide range of molecular tactics to withstand antimicrobial pressure, which leads to antibiotic resistance. Treatment is made more difficult by the multidimensional resistance phenotypes that result from these mechanisms’ frequent overlap rather than their isolation [21]. The molecular landscape is dominated by four main categories: active efflux pumps, altered drug targets, decreased drug permeability, and enzymatic drug inactivation. Each mechanism highlights the critical need for new therapeutic approaches and reflects the adaptability of bacteria.

β-lactamases: These enzymes make penicillins, cephalosporins, and carbapenems inactive by hydrolysing their β-lactam ring. Because of their wide substrate range and widespread distribution, extended-spectrum β-lactamases (ESBLs) and carbapenemases like KPC, NDM, and OXA-type enzymes are especially dangerous [22]. Enzymes that modify aminoglycosides (AMEs): In order to stop aminoglycosides from attaching to ribosomal targets, bacteria produce acetyltransferases, nucleotidyltransferases, and phosphotransferases. These enzymes contribute to high-level resistance in Pseudomonas aeruginosa and Enterobacteriaceae [23]. Figure 1 illustrates two major biochemical mechanisms by which β-lactamase enzymes inactivate β-lactam antibiotics:

Panel A: Mechanism of serine β-lactamase

In this process, the antibiotic’s β-lactam ring is attacked by a serine residue in the enzyme’s active site, creating a covalent acyl-enzyme intermediate. Water quickly hydrolyses this intermediate, producing an inactive antibiotic molecule. Class A, C, and D β-lactamases, which are present in Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli, share this mechanism [24].

Panel B: Mechanism of metallo-β-lactamase

On the other hand, a zinc ion (Zn²⁺) coordinated by histidine residues is used by metallo-β-lactamases (MBLs) to activate a water molecule that hydrolyses the β-lactam ring directly. Class B enzymes like NDM, VIM, and IMP, which are common in strains resistant to carbapenem, exhibit this non-covalent mechanism [25].

Alteration of Drug Target

Ribosomal mutations: Aminoglycoside and macrolide resistance is conferred by mutations in 16S rRNA or ribosomal proteins. For instance, macrolide binding is inhibited when erm genes methylate 23S rRNA [25].  Changes in penicillin-binding proteins (PBPs) decrease the binding of β-lactam antibiotics. PBP2a, which has a low affinity for β-lactams, is encoded by the mecA gene in methicillin-resistant Staphylococcus aureus (MRSA) [26].

DNA gyrase and topoisomerase IV mutations: Point mutations in the gyrA and parC genes that change the quinolone-binding pocket cause fluoroquinolone resistance. There have been more reports of these mutations in Klebsiella pneumoniae and Escherichia coli [27].

Reduced Drug Permeability

The outer membrane of gram-negative bacteria serves as a selective barrier. Loss or remodelling of porins can lead to resistance, which lowers the influx of antibiotics.
Porin loss: In E. coli, mutations or downregulation of porins like OmpF and OmpC restrict the entry of β-lactams and fluoroquinolones [28]. Membrane remodelling: Permeability can be decreased by structural alterations in lipid composition. To withstand polymyxins, for instance, Pseudomonas aeruginosa alters its outer membrane [29].

Active Efflux Pumps

Antibiotics are actively removed from bacterial cells by efflux pumps, which reduces intracellular concentrations. They fall into the following major families namely; ATP-binding cassette (ABC) transporters which exports medications by hydrolysing ATP and
Major Facilitator Superfamily (MFS) whose transport is dependent on the proton motive force [30].

Resistance-nodulation-division (RND) family: Common in Gram-negative bacteria, such as MexAB-OprM in P. aeruginosa and AcrAB-TolC in E. coli [31]. Broad-spectrum resistance is provided by efflux pumps, which frequently overlap with other mechanisms. Global stress responses and transcriptional regulators are involved in their intricate regulation [32]. Figure 2 depicts the structural organisation of the AcrAB-TolC multidrug efflux pump, a prototypical RND-family system in Gram-negative bacteria:

The AcrAB-TolC multidrug efflux pump, a model RND-family system in Gram-negative bacteria, is shown structurally in Figure 2: A channel is created through the outer membrane by TolC (blue). The substrate transporter is AcrB (purple), which is embedded in the inner membrane. AcrA (green) connects AcrB to TolC and stabilises the complex by bridging the periplasmic space [15].

A variety of antibiotics, such as fluoroquinolones, β-lactams, and chloramphenicol, are actively expelled from the cytoplasm to the external environment by this tripartite system using the proton motive force. These elements work together to guarantee effective drug clearance and promote multidrug resistance [5, 10, 22].

Genetic Basis of Resistance

Antibiotic resistance has deep roots in the genetic makeup and evolutionary dynamics of bacterial populations, making it more than just a biochemical phenomenon. Both chromosomal mutations and horizontal gene transfer (HGT), which together propel the emergence and dissemination of resistance traits across various microbial communities, are included in the genetic basis of resistance [23]. Furthermore, biofilms act as ecological niches that promote gene exchange and shield resistant phenotypes, increasing the persistence of resistance in environmental and clinical contexts.

Mutations in the Chromosome

The structure or function of antibiotic targets can be changed by chromosomal mutations, which are induced or spontaneous changes in bacterial DNA. Reduced drug binding or changed cellular pathways can result from these mutations, which can happen in genes encoding ribosomal proteins, DNA gyrase, RNA polymerase, or metabolic enzymes [24].

Target site mutations: For instance, by altering the quinolone-binding site of DNA gyrase and topoisomerase IV, point mutations in the gyrA and parC genes provide resistance to fluoroquinolones [25]. Similarly, by changing the RNA polymerase β-subunit, mutations in the rpoB gene cause rifampicin resistance in Mycobacterium tuberculosis [26].

Regulatory mutations: By altering promoter regions or transcriptional regulators, resistance can be indirectly increased by upregulating efflux pumps or downregulating porins. For example, in Escherichia coli, mutations in the marR gene increase the expression of the AcrAB-TolC efflux system [27].

Fitness compensation: Bacteria frequently acquire compensatory mutations that restore growth rates without losing resistance, enabling long-term persistence, even though resistance mutations may impose fitness costs [28].

Table 3 displays Resistance genes encode proteins or mutations that counteract the effects of antibiotics through target modification (e.g., mecA, rpoB, gyrA), drug inactivation (e.g., β-lactamases, aminoglycoside-modifying enzymes), or alternative pathways (e.g., sul genes, tet genes). They are essential to the worldwide antimicrobial resistance crisis because their presence on plasmids, transposons, and integrons speeds up their spread throughout bacterial populations.

Horizontal Gene Transfer

The transfer of genetic material between organisms outside of conventional reproduction is known as horizontal gene transfer. It facilitates the quick spread of resistance genes among species and genera and is the main cause of acquired resistance Figure 3.

Plasmids
Extrachromosomal DNA elements known as plasmids are capable of independent replication and frequently contain several resistance genes. Transfer machinery that enables direct gene exchange between cells is encoded by conjugative plasmids. In Enterobacteriaceae, extended-spectrum β-lactamases (ESBLs) like bla_CTX-M, bla_TEM, and bla_SHV are frequently plasmid-borne [29]. Additionally, plasmid-encoded, carbapenemases such as bla_NDM, bla_KPC, and bla_OXA-48 have spread throughout the world, especially in Klebsiella pneumoniae and Acinetobacter baumannii [30].

Transposons
DNA sequences known as “jumping genes,” or transposons, are able to travel both within and between genomes. They frequently have insertion sequences and resistance genes that help them integrate into chromosomes or plasmids. Multidrug-resistant strains often contain Tn3 family transposons, which carry β-lactamase genes. Tn7 and Tn10 integrate into conserved chromosomal sites and carry genes for tetracycline and aminoglycoside resistance, respectively [32].

Integrons

Gene cassettes, including resistance determinants, are captured and expressed by integrons, which are genetic platforms. They are made up of a promoter that controls cassette expression, an integrase gene (intI), and a recombination site (attI). The most clinically significant integrons are class 1 integrons, which frequently carry several resistance cassettes, including aadA, dfrA, and sul1, which provide resistance to trimethoprim, aminoglycosides, and sulfonamides [11].

Role of Biofilms in Gene Dissemination

Structured microbial communities embedded in an extracellular matrix that they produce themselves are known as biofilms. They develop on tissues, medical equipment, and environmental surfaces, giving bacteria a safe haven.

Physical defence: The biofilm matrix inhibits the penetration of antibiotics and produces oxygen and nutrient gradients, which trigger stress reactions that increase tolerance [16].

Enhanced HGT: Because biofilms promote stable microenvironments and close cell proximity, conjugation, transformation, and transduction occur more frequently. Compared to planktonic cultures, biofilms have much higher plasmid transfer rates [30].
Resistance persistence: Biofilm-resistant cells are able to withstand therapy and spread infections. For instance, multidrug-resistant subpopulations that avoid immune clearance are present in Pseudomonas aeruginosa biofilms in the lungs of people with cystic fibrosis [33].

Clinical and Public Health Implications

Not only is antibiotic resistance a molecular or genetic phenomenon, but it also directly affects patient outcomes, healthcare costs, and global health security in clinical practice and public health systems. The ramifications are extensive, encompassing the emergence of resistant pathogens in hospitals and communities, treatment failure in individual patients, and the wider ecological aspects encompassed by the One Health viewpoint.

Unsuccessful Treatment

Treatment failure, where conventional therapies lose their effectiveness against resistant pathogens, is one of the most direct clinical effects of antibiotic resistance. Longer illness, a higher chance of complications, and higher death rates are the results of this failure. For instance, infections brought on by methicillin-resistant Staphylococcus aureus (MRSA) or carbapenem-resistant Klebsiella pneumoniae frequently call for last-resort medications like colistin or linezolid, which may be more toxic and less effective [21]. Additionally, treatment failure raises healthcare expenses and lengthens hospital stays. Multiple rounds of therapy, combination regimens, or experimental treatments are frequently required for resistant infections, placing a burden on healthcare resources. Multidrug-resistant tuberculosis (MDR-TB), which necessitates prolonged treatment courses with second-line medications that are less effective and more costly, is caused by resistance to rifampicin and isoniazid [12].

Resistance Acquired in a Hospital versus the Community

Hospital-acquired (nosocomial) and community-acquired antibiotic resistance present in different ways, each with unique clinical and epidemiological ramifications.

Hospital-Acquired Resistance

Because of their high antibiotic usage, invasive procedures, and susceptible patient populations, hospitals are hotspots for resistant pathogens. MRSA, multidrug-resistant Acinetobacter baumannii, and carbapenem-resistant Enterobacteriaceae are common hospital-acquired resistant organisms [13]. These infections are challenging to prevent and treat because they are frequently linked to catheters, ventilators, and surgical wounds. Because resistant infections greatly raise mortality rates in intensive care units, the burden is especially severe there.

Community-Acquired Resistance

Hospitals are no longer the only places where resistance occurs. Pathogens that spread widely outside of healthcare settings include resistant Neisseria gonorrhoeae and community-acquired MRSA (CA-MRSA). Resistant UTIs brought on by ESBL-producing E. coli are becoming more frequent in many areas among otherwise healthy people [14]. Widespread antibiotic abuse, such as self-medication, incomplete courses, and over-the-counter access without a prescription, is reflected in community-acquired resistance.

One Viewpoint on Health

In addressing antibiotic resistance, the One Health framework highlights the interdependence of environmental, animal, and human health. Due to the use of antibiotics in veterinary care, agriculture, and environmental contamination, resistance genes and pathogens spread throughout these domains.

Human health: Overprescription and clinical abuse of antibiotics hasten the development of resistance in pathogens like Mycobacterium tuberculosis and Streptococcus pneumoniae.
Animal health: Antibiotics are frequently used to prevent disease and promote growth in livestock. This procedure favours resistant bacteria that can spread to humans through food chains, such as Salmonella and ESBL-producing E. coli [21].

Environmental health: Hospital waste, pharmaceutical production, and agricultural runoff all introduce antibiotic residues and resistant bacteria into soil and water systems. These environments serve as reservoirs for resistance genes, which can be transferred to human pathogens via horizontal gene transfer [15].

Strategies to Combat Antibiotic Resistance

The growing threat of antibiotic resistance calls for creative, multidimensional approaches that go beyond conventional drug development. Although the 20th century saw the discovery of antibiotics, their abuse and overuse have accelerated resistance, leaving doctors with fewer treatment options. Antibiotic stewardship, the creation of new antimicrobials, and the investigation of alternative treatments like phage therapy and CRISPR-based interventions are the main strategies used today to fight resistance. When combined, these tactics signify a paradigm change in the direction of precision-driven and sustainable infection control.

Antibiotic Stewardship

Antibiotic stewardship programs (ASPs) are designed to optimize antibiotic use, ensuring that patients receive the right drug, at the right dose, for the right duration. Stewardship is critical in reducing unnecessary prescriptions, curbing misuse, and slowing the emergence of resistance. Evidence shows that ASPs significantly decrease inappropriate antibiotic use in hospitals and improve patient outcomes without increasing mortality [28]. In community settings, stewardship involves public education, stricter regulation of over-the-counter sales, and integration of rapid diagnostic tools to guide therapy. As summarised in Table 4, stewardship remains the most immediate and cost-effective strategy, reducing misuse and preserving antibiotic efficacy for future generations.

Novel Antimicrobials

Despite the urgent need, the pipeline for new antibiotics has remained limited. However, recent advances in genomics, synthetic biology, and natural product discovery have reinvigorated antimicrobial research. Novel agents such as teixobactin, which targets lipid II and lipid III in bacterial cell walls, show promise against multidrug-resistant Gram-positive pathogens [17]. Similarly, antimicrobial peptides (AMPs) derived from host defence proteins are being explored for their broad-spectrum activity and reduced likelihood of resistance development [20]. Another promising avenue is the use of non-traditional therapeutics, including anti-virulence drugs that disarm pathogens rather than kill them, thereby reducing selective pressure for resistance [3]. As highlighted in Table 4, these novel antimicrobials expand the therapeutic arsenal by introducing new targets and mechanisms that circumvent conventional resistance pathways.

Phage Therapy

Bacteriophages, viruses that infect and kill bacteria, are re-emerging as viable alternatives to antibiotics. Phage therapy offers specificity, targeting particular bacterial strains while sparing commensal microbiota. Clinical trials have demonstrated phage efficacy against resistant pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus [17]. Moreover, phages can be engineered to enhance their lytic activity or deliver antimicrobial payloads. Unlike antibiotics, phages evolve alongside bacteria, potentially overcoming resistance mechanisms. However, challenges remain, including regulatory hurdles, variability in phage-host interactions, and the need for personalised phage cocktails. As shown in Table 4, phage therapy represents a promising adjunct to conventional treatment, particularly for multidrug-resistant infections where traditional antibiotics fail.

CRISPR-Based Approaches

CRISPR-Cas systems, originally discovered as bacterial adaptive immune mechanisms, are now being harnessed to combat resistance at the genetic level. CRISPR-based antimicrobials can selectively target and cleave resistance genes, effectively resensitizing bacteria to antibiotics [7]. For instance, CRISPR-Cas9 constructs delivered via plasmids or phagemids have been used to eliminate blaNDM-1 and mecA genes, restoring susceptibility in resistant strains. Beyond gene editing, CRISPR can be applied for rapid diagnostics, enabling precise detection of resistance determinants in clinical samples [24]. As summarised in Table 4, CRISPR-based approaches represent a cutting-edge strategy, offering precision medicine solutions that directly reverse resistance rather than merely bypass it.

Conclusion

One of the most urgent issues facing contemporary medicine is antibiotic resistance, which threatens the security of global health and undermines decades of advancements in the control of infectious diseases. The remarkable adaptability of bacteria under selective pressure is demonstrated by the molecular and genetic mechanisms underlying resistance, which range from enzymatic drug inactivation and target modification to decreased permeability and efflux pump activity. These processes are further amplified by chromosomal mutations, horizontal gene transfer, and the ecological resilience of biofilms, creating a dynamic and interconnected resistome that transcends clinical boundaries. The clinical implications are profound, manifesting in treatment failures, prolonged hospitalisations, and increased mortality, while the public health burden extends across hospitals, communities, and ecosystems.

In the future, a comprehensive and integrated strategy will be necessary to combat antibiotic resistance. Antibiotic stewardship, which makes sure that current medications are used wisely and efficiently to slow the rate of resistance, must continue to be crucial. In order to replenish the diminishing therapeutic pipeline, investment in novel antimicrobials, such as agents that take advantage of new bacterial targets or harness host defence peptides, is crucial. A new era of customised antimicrobial therapy is being ushered in by alternative approaches like bacteriophage therapy and CRISPR-based interventions, which offer precision tools capable of directly targeting resistant pathogens or removing resistance genes.

The management of antibiotic resistance ultimately rests on the continued cooperation of researchers, physicians, legislators, and communities. Science cannot solve resistance on its own; political will, public participation, and international solidarity are all necessary. Antibiotic effectiveness can be maintained for future generations if stewardship, innovation, and ecological consciousness come together to change the course of resistance. The opportunity to transform the future of infectious disease treatment through teamwork and scientific creativity is just as great as the enormous challenge.

Acknowledgement

We thank all the researchers who contributed to the success of this research work.

Conflict of Interest

The authors declared that there are no conflicts of interest.

Funding

No funding was received for this research work

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