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ROLE OF NANOPARTICLES IN THE EFFICACY OF ANTIBIOTICS  
  

  

1Muhammad Ukashah, 2Bareera Ijaz, 3Muhammad A. Riaz, 4Muhammad K. Javed   
1Department of Biotechnology University of Sargodha, Sargodha  
2Center for Agriculture Biochemistry & Biotechnology University of Agriculture Faisalabad  
3Center for Agriculture Biochemistry & Biotechnology University of Agriculture Faisalabad  
4Institute of Molecular Biology & Biotechnology Bahauddin Zakariya University Multan  

 

Abstract: Now a day, the reason of greater mortality rate is due to bacterial diseases. The cure of bacterial 

diseases is the use of antibiotics but there is a problem that bacteria have become multidrug resistant and so 

antibiotics can’t be used for treating bacterial diseases. A great revolution in this aspect is the use of 

nanoparticles. Nanoparticles can be made from different metals like gold, copper, zinc etc. The mode of action 

of nanoparticles is that they enter into the cell membrane of pathogen and affect their molecular pathways. 

Nanoparticles are used in combination with different drugs. The nanoparticles which have been extensively 

studied are silver nanoparticles.  Experiments were performed of check the efficiency of silver nanoparticles 

in gram positive and gram negative bacteria. Silver nanoparticles were not used with the combination of any 

drug. Nanoparticles are stable for long time as they are surrounded by capping layers because of which they 

are stable for long time. Another important function of these capping layers is that they are also providing 

active surface area for the interaction with other biological components. Shortly, we can say that nanoparticles 

can be used as an alternative to antibiotics and they can serve us in better way.  

  

Introduction: The term antibiotic is derived from the word “antibiosis” which means (against life). When we 

look on the definition of antibiotics these are defined as chemical compounds that can either kill or inhibit the 

growth of bacteria or other pathogens. These antibiotics can be antifungal, antibacterial or antiviral. However, 

in general terms the term antibiotic is used for antibacterial compounds. These antibiotics are used to treat 

bacterial disease. Their mode of action is to either interfere with DNA, RNA or protein of the host. The 

bacterial diseases are lethal as they can cause death. Recently, the greater mortality rate is due to bacterial 

diseases as due to the rapid use of these antibiotics the bacteria has developed resistance against these 

antibiotics. The main reason of resistance to antibiotics is horizontal gene transfer which is by means of biofilm 

creation, transformation, transduction or bacterial conjugation.  

The complete removal of resistance is necessary in order to compete with bacterial diseases. Both gram 

positive and gram negative bacteria can create biofilms on medical apparatus. The bacteria related to human 

diseases are Enterococcus faecalis, Staphylococcus epidermidis, E.coli and many more other bacteria. The 

greater revolution in this aspect is the use of nanoparticles. These nanoparticles can be effectively used in the 

treatment of different bacterial and infectious diseases. The nanoparticles are metallic in nature and the metals 

used are gold, silver or zinc etc.   

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In order to inhibit the growth of pathogenic microbes the ions used are copper and cobalt. The complexes of 

metals are also used to inhibit growth of pathogens that can cause diseases. The nanoparticles are used in 

combination with the different drugs in order to cure bacterial and other infectious diseases. The nanoparticles 

that are extensively studied are silver nanoparticles. In this review article we will study how nanoparticles are 

used in the treatment of different diseases as an alternative to antibiotics.  

Antibiotic Resistance:  

Antibiotics were first discovered by Sir Alexander Fleming in 1928. At that time the antibiotics were the only 

possible solution to treat different diseases. The first antibiotic discovered was “Penicillin”. Later on, these 

drugs were extensively used and because of their extensive use the bacteria developed resistance to these drugs 

leading to higher mortality rate. Resistance genes were transferred to progeny in order to transfer resistance 

to next progeny. This type of resistance is known as “acquired resistance”.  

Another type of resistance is “intrinsic resistance”. In this type of resistance the genetic traits don’t depend 

on the exposure to antibiotic that was previously done. Resistance is the development of different molecules 

that are utilized when pathogen is exposed to any drug.   

As the bacteria have developed multidrug resistance the pharmaceutical companies are not focusing greatly 

on the development of new antibiotics. Those bacteria that are multidrug resistant meaning when they are 

exposed to different antibiotics they show resistance and be killed, the bacteria of this type are known as  

“Super bugs”.   

More than 35000 people are subjected to death every year because of the multi drug resistant bacteria. This is 

an alarming situation as we have never won war against microorganisms. If we want to eliminate this situation 

we have to do something as soon as possible.  

The alternative to this alarming situation is the use of Nanoparticles which can effectively eliminate this 

situation.  

Mechanisms of Antibiotic Resistance:  

Here we will discuss some of the mechanisms of antibiotic resistance. These mechanisms are divided into 

following categories.  

 Enzymatic Inhibition:  

This type of inhibition happens when the antibiotics that are used are being neutralized by bacteria before 

these drugs can perform their action. The antibiotics beta lactam is targeted at transpeptidase enzymes which 

are playing their role in the synthesis of cell walls by the breakage of amide bonds of the four members[1-3]. 

In case of gram negative bacteria the genes of beta lactamase are present inside the periplasmic space but in 

case of gram positive bacteria in them beta lactamase is excreted [4].   

The genes of beta lactamase are present in transposons or plasmids that result in swift movement and the 

genetic material is conveyance to alternative bacteria. The additional changes to these genes of beta lactamase 

result in the systems that are for multidrug resistance that consist of sulphonamides, macrolides, 

aminoglycosides and chloramphenicol.  

  

  

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 Target Site Alteration:  

The alteration of target site occurs when the product of target gene of antibiotics is changed and the interaction 

between the bacteria and drug is avoided. There are both 30S and 50S ribosomes which are the target for 

antibiotic [7-8].  

Both of these ribosomes permit the changes and because of these changes permit the cells of bacteria of the 

maintain their homeostasis even during the presence of any antibiotic [10].  

 Alteration of a Metabolic Pathway:  

Sulphonamides are the example of inhibition which occurs in dihydropteroate synthase present in folic acid. 

Folic acid and nucleic acid can be synthesized by using PABA which confirms resistance in sulphonamide 

bacteria [12].  

The antibacterial activity of antibiotic can be inhibited by activating PABA [14-15]  

Membrane Permeability Shifts:  

The membrane of bacteria is made up of transport proteins, phospholipids and lipopolysaccharides. The 

hydrophobic antibiotics penetrate the membrane and then enters into the cell [15, 16].  When we change the 

penetrability of the membrane the arrangement of lipopolysaccharides is changed. If there is the expression of 

entire length of polysaccharides than the strains of bacteria show resistance to antibiotic [17, 15].  

These strains which are resistant to antibiotic limit the penetration of the hydrophobic antibiotics.   

Experimental:  

The alternative to antibiotics is the use of metallic nanoparticles. Here we will discuss the preparation of 

nanoparticles through some examples.  

 Preparation of citrate capped gold nanoparticles:  

Take boiling solution of the HAuCl4.6H2O, distilled water and trisodium citrate because of this addition the 

color of solution gold chloride that was yellow than turned into wine red and show absorbance at 518nm at 

UV spectrum. The diameter of these nanoparticles is 12-15 nm.  

 Preparation of antibiotic coated gold nanoparticles:  

In the preparation of drug coated nanoparticles following steps are performed. The stabilized 0.1 mM citrate 

gold nanoparticles were mixed with 5cm3 of 3mM drugs in water and then stir them for 2h. Two different 

concentrations of gold particles 0.3mM and 0.5mM were prepared.  

 Preparation of Co nanoparticles:  

In order to prepare cobalt nanoparticles reduce a cobalt (2) salt by using a reducing agent hydrazine hydrate. 

Take 10 gram of cobalt chloride and dissolve it into 150ml of ethylene glycol and water and then stir the 

solution until it is dissolved completely. Adjust the Ph of the solution to 12 by adding NaOH solution. Than 

treat the solution of cobalt chloride with 50% of hydrazine hydrate.   

After that centrifugation of reaction mixture is carried out. Than collect the black particles and wash it with 

water in order to remove chloride, sodium and hydrazine. Than dry the final product in oven at 60C.   

  

  

  

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 Preparation of Silver nanoparticles:  

Take 1.2% of metallic silver and than stabilize it with 18.8% of PVP (polyvinyl chloride) in water. When 

observed on UV spectrum they show absorbance at 400nm. The shape of silver nanoparticles is sphere and 

diameter is 35 -15nm.   

 Preparation of ZnO nanoparticles:  

Take 0.2 gram of the CTAB and than add it into the bi-distilled water in a flask. Take 10mL of the 

Zn(CH3COO)2.2H2O was added into the solution. Than stir the solution at different conditions. Add NaOH 

drop wise and after that the solution turns milky. Than retain the solution for half hour and cool it, than 

centrifuge and dry it at room temperature and thanwash with methanol and water.   

 Bismuth based nanoparticles:  

Bismuth is a brittle and crystalline metal, and when we freeze this metal it expands. Its thermal conductivity 

is low than any other metal. This method of preparation of nanoparticles is cost effective and can be employed 

on industrial scale. These bismuth based nanoparticles are used in the treatment against different pathogens.  

 Gold based nanoparticles:  

The gold combinations can be used in the treatment of different diseases like juvenile arthritis, palindromic 

rheumatism, rheumatic diseases [84]. Apparently gold nanoparticles have no antibacterial activity, Vidya et 

al .[85] synthesized and than functionalized in a process in which antibiotics of third generation are used and 

also of second generation.  

Nanoparticles As Antimicrobial Agents:  

The number of first line antibiotics is decreasing and the number of last line antibiotics is increasing in order 

to treat infectious diseases thus, decreasing the options of treatment for patients. Nanoparticles can be used in 

combination with the different antibiotic drugs. For example, silver nanoparticles used in combination with 

drugs can be used to overcome bacterial resistance.   

When we observed the effect of silver nanoparticles used in combination with antibiotics like vancomycin, 

amoxicillin and erythromycin showed that this combination is effective only against gram positive bacteria 

[34]. Deng showed that when silver nanoparticles alone were used they resulted in antibacterial activity against 

Salmonella typhinium.  

When the complex of tetracycline-silver nanoparticles were used it showed elevated drug action because of 

the accumulation of silver outside the cell and this inhibited the action of bacteria. Banoee and his colleagues 

when used zinc oxide it showed increased antibacterial activity against S.aureus and E.coli [36]. It was 

observed that if we use zinc oxide nanoparticles combined with nitrofurantoin and amoxicillin than 

antibacterial activity was decreased against S.aureus and E.coli. This combination with drugs not all the times 

the antibacterial activity is increased it can also be decreased depending on the drug and nanoparticles [36].  

Mechanisms of drug resistance to antimicrobials:  

These mechanisms are as follows:  

 Decreased Uptake:  

When drugs uptake is decreased than it does not allow the storage of drugs in cells to such level that is not 

effective for the killing of cells. Bacteria contain the resistance genes against specific antibiotics. For example, 

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gram negative and gram positive bacteria possesses genes for tetracycline TetK, TetB, TetA. Under native 

conditions the TetA gene is repressed by its repressor gene TetR.   

When tetracycline binds to TetR and then inactivates it and TetA is expressed. The TetA gene than flushes 

out tetracycline making the bacteria resistant to tetracycline. Other such examples of resistance are resistance 

against fluoroquinolones in gram negative bacteria and also the resistance against macrolide in gram positive 

bacteria [5]. Examples of less uptake of drugs include resistance against aminoglycoside in gram negative 

bacteria.  

 Alteration of Antimicrobial Target:  

In bacteria, resistance is also developed by expressing genes that codes for alternative version for antibiotic 

target. The wild type versions have more binding affinity than altered substrates so altered substrates can 

decrease the activity of antibiotics. For example, Staphylococcus aureus is resistant to methicillin. In case of 

PBP2A and PBP the beta lactam has low binding affinity and mccA confers resistance against beta lactams 

[5,38,39].  

The resistance against glycopeptides is conferred by gene vanA which is involved in the expression of enzyme 

known as D-alanine D-lactate ligase. The peptidoglycan precursor D-ala-D-ala is converted into D-ala-

Dlactate by this enzyme. The wild type version of this precursor is 1000 times greater than this modified 

precursor and thus showing resistance towards vancomycin [5 , 40]. Other examples are sulfonamide 

resistance in E.coli, resistance in gram positive and gram negative bacteria against quinolones [5, 41].  

 Modification of Antimicrobial Drugs:  

Bacteria also has resistance genes that code for enzymes that modify antibiotic. For example, the acetylation 

of NH2 group of aminoglycoside is catalyzed by ACT N-acetyltransferase, the phosphorylation of OH group 

of aminoglycoside catalyzed by APH O-phosphotransferase, the adenylation of OH group of aminoglycoside 

catalyzed by ANT O-adenyltransferase. In all these cases it is observed that due to modification the affinity 

of antibiotics is reduced, the antimicrobial activity is also reduced by 30S ribosomal subunit. The development 

of chloramphenicol resistance is done by inactivation of chloramphenicol by acetyltransferases.   

 Production of Competitive Inhibitor:  

A competitive inhibitor is also produced to develop antibiotic resistance. For example, species like S.aureus 

and N.meningitides both produce enhanced concentration of PABA that is involved in competition with 

sulfonamide for its target that is dihydropteroate synthetase and thus developing resistance against 

sulfonamide drugs.  Persister Cells:  

When small number of bacteria slow down their metabolic activity when they express toxin-antitoxin and then 

they become more tolerant towards antimicrobial drug. Such type of cells is known as persister cells. When 

bacterial population is exposed to antibiotics than most of the bacteria are killed leaving behind the persisters. 

When the metabolic activity of persisters is resumed than the chances of reoccurrence of infection are there 

[5, 36].  

  

  

  

 Biofilm Formation:  

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When the bacterial cells attach to medical implants and human tissues than they immobilize themselves. Due 

to the presence of extracellular polymeric substance around the bacterial cells the treatment of infections that 

are associated with biofilm are difficult to treat. This EPS matrix is resistant towards many antibiotics thus 

causing chronic infections in humans [5, 43]. The barrier between bacterial cells and antibiotics is caused by 

this EPS matrix.   

The molecules that have greater size than a certain size, also including antibiotics, are unable to pass through 

this EPS matrix. In case of antibiotics because of their negative charge they are also trapped into EPS matrix. 

In EPS matrix certain enzymes are present that reduces the affinity of antibiotics. If the concentration of 

antibiotics below their MIC value than EPS matrix also develops resistance in bacteria [5, 44].  

 Swarming:  

In case of bacteria the multicellularity observed is known as swarming. This situation occurs when on 

semisolid surfaces the swarm cells come together as a single unit. In case of planktonic cells they are elongated 

and then develop multiple flagella. The swarm cells migrate with each other like raft. These swarm cells are 

resistant towards several antibiotics. When we culture the swarm cells in a liquid media they restore their 

susceptibility towards antibiotics [5, 38].  

 Intracellular Microbes:  

As the drugs have limited affinity to enter into the bacterial cells so, when the intracellular microbes are inside 

the host cells they are protected [5].   

 Factors which affect antimicrobial activity: Size:  

The size of nanoparticles is important in this aspect that this determine the degree of penetration of 

nanoparticles in the bacterial cell wall. This has direct correlation with the degree to which the nanoparticles 

penetrate into the cell wall. The mechanism of action through which the nanoparticles adhere to the surface of 

cell wall also depends on the type of nanoparticles being used.  

The nanoparticles of size 50nm can penetrate beyond the cell wall and can also target the DNA that is present 

inside the cell. Morones and his colleagues observed that the silver nanoparticles having the size 10nm have 

the ability to penetrate bacteria and showed antimicrobial action [66]. Hsueh and his colleagues reported the 

activity of silver nanoparticles against Bacillus subtilis [51].   

Besides the size, the morphology of nanoparticles is also important in their affectivity. Sadeghi and his 

reporters showed the activity of silver nanoparticles against S.aureus and E.coli [67]. They also observed that 

regardless of shape the activity of nanoparticles can be achieved. So, this one showing that morphology is not 

playing an important role in the activity of nanoparticles [67].  

Zeta potential:  

Zeta potential is also important in the antimicrobial activity of nanoparticles. Zeta potential determines the 

interaction of nanoparticles with the surface of bacterial cell wall [68]. Zeta potential also determines that how 

nanoparticles can be used as drug carriers. This zeta potential also determines the pharmacokinetic behavior 

of the nanoparticles, it is important because of the ph changes that occur inside the body that can affect the 

charge of nanoparticles.  

In case of bacteria, this zeta potential determines that how much associations and repulsions occur between 

the bacterial cell and the nanoparticles [69]. In case of gram positive bacteria teichoic acid is present on the 

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cell surface and inn case of gram negative bacteria, lipopolysaccharides are present on the cell surface [9].  

These components present on the surface of cell affect the stability of nanoparticles. As in case gram negative 

bacteria most of the cell surface is covered with LPS which gives negative charge to the surface. This negative 

charge explains that why nanoparticles rather than penetrating the prokaryotic cell they accumulate on their 

surface [71]. In case of bacteria that are susceptible to antibiotic the antibiotics like aminoglycosides which 

are lipid soluble they can easily penetrate.  

In case of MDR bacteria the composition of cell wall is changed in order to prevent the entry of antibiotics 

inside the cell wall [73]. Due to opposite charges the nanoparticles remain on the surface of cell wall [75].   

Pharmacokinetic And pharmacodynamic Characteristics Of Nanoparticles:  

The pharmacokinetics of nanoparticles depend on different factors like surface charge, size, surface coating, 

exposure route, animal species and dose. Their comprehensive study of these factors is important for biosafety 

and risk assessment in clinical practice [Lin et al, 20150]. Most of the nanoparticles are distributed into spleen 

and liver but silver nanoparticles can be modified to enhance the distribution of these nanoparticles towards 

the specific organ [Lin et al, 2015].  

 Dose Optimization:  

The optimum dose is very important for treating any disease and minimizing the toxic effects of the drugs 

[Khan et al., 2016; Hua et al., 2018]. The dose of nanoparticles to kill the cell is very high and we can’t apply 

this higher dose to humans. The data that we collect from animal studies cannot be applied directly to humans 

[Khan et al., 2016; Hua et al., 2018]. Experiments are being applied on adult volunteers to observe which dose 

is effective in treatment and these studies are continue.   

 Clearance and Elimination;  

Nanoparticles can be long term accumulated in the spleen and liver [Lin et al, 2015]. Nanoparticles are not 

biodegradable and they can accumulate into tissues for long time [Zaidi et al., 2017]. A greater accumulation 

of nanoparticles has been observed in the kidneys but the reason for this accumulation was that less number 

of large nanoparticles were present as their greater concentration was accumulated in liver and spleen [Hoshyar 

et al., 2016].  

 Toxicity:  

In terms of toxicity the nanoparticles themselves and their degradation products cause toxicity as they cause 

hemolysis and also interfere with coagulation pathways of blood [Kandi and Kandi., 2015]. The toxic 

complications that are caused by nanoparticles, their exact mechanism is unknown but it is observed that large 

size of nanoparticles is the cause of toxicity [Dos Santos et al., 2014].  

When the toxicity of nanoparticles is studied, the extensive study is performed on silver nanoparticles and 

these nanoparticles have proven to be more toxic against cells [Bondarenko et al., 2013; lvask et al., 2014].  

The accumulation of silver nanoparticles in lungs, liver and spleen and in other organs result in the damage of 

organs and their loss of function [Hemeg, 2017].  

These nanoparticles can also be accumulated in bone marrow, lymphatic system, liver and spleen [Hagens et 

al., 2007] and also their inhalation  may cause cytotoxicity in the organs like lungs [Leucuta, 2013]. No life 

threatening toxicity is caused by nanoparticles [Pfurtscheller et al, 2014; Sengupta et al, 2014; Wei et al, 2015; 

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Zazo et al, 2016].The evaluation of toxicity is important for clinical practices and in order to check any 

therapeutic effect [Khan et al, 2016].  

 Targeted antibiotic therapies:  

The infection site of bacteria is rich in molecular and physiological cues that are useful in the release of drug 

and also support the attachment of nanoparticles to bacteria. There are three ways for targeted drug delivery 

which are physical-chemical gradients, Passive targeting and active targeting. 71,72In case of passive targeting 

there is dysfunctional lymphatic drainage and also enhanced permeability and these changes occur at infection 

site.  

At the surface of gram negative bacteria, the negative charge is present and that negative charge can be used 

to affect target site but some bacteria can resist this by secreting acetic acid and lactic acid.82 In order to 

overcome this problem, many groups have developed micelles in order to switch charge and also the 

nanoparticles that affect the cell wall that has negative charge.83,84  

A ph sensitive polymer that is zwitterion is used that can slow down the growth of S.aureus and E.coli at low 

ph.85 In order to synthesize nanoparticles and the micelles that can switch the charge this includes beta-

amino ester,86 poly-L-histidine,84 and many other chemical functionalities.87   

Nanoparticles can be used to treat bacterial infections in stomach but the challenge in this aspect is that to 

develop nanoparticles that can work at various ph values in gastrointestinal tract. In addition to problems of 

ph gradients and negative charge, the bacteria can also secrete several virulence factors like collagen 

adhesions, toxins, fibronectin and many enzymes.97 The simplest way to target the infection site is to dope the 

surface of delivery vehicle with antibody.   

If the bacteria either facultative or obligate escapes the site of infection than the chances of reoccurrence of 

this infection increases. It is now observed that bacteria can escape by hiding in the phagocytic cells, 

osteoblasts and erythrocytes.9 The role of these pathogens is that they disrupt the microbicidal mechanism of 

phagocytic cells by interfering with the fusion of phagosomes with lysosomes thus increasing the duration of 

their survival.102  

Many of the pathogenic bacteria have been discovered who can perform this function and their examples are 

B.pseuomallei. S.aureus, M.tubercolosis.10  The cytoplasm of mammalian cells is used by the pathogens  to 

exchange resistance and virulent genes.103 When a macrophage is infected, than in next step the intracellular 

pathogen is targeted. Xiong et al,20 the optimum activity of any antibiotic against any cell which is infected by 

bacteria is dependent on the quantity of active drug inside the subcellular compartments, which in turn depends 

on the activity, subcellular distribution and cellular retention.  

One method to achieve this is to distribute this antibiotic to infection site or to cell should be through 

biodegradable vehicle. Many biodegradable delivery systems consist of synthetic or natural polymers like 

CS78 and albumin can be used for this purpose. The major infection site is found in liver and spleen. Outside 

the liver and spleen the macrophages that are infected by bacteria are also present in pulmonary cavities.112 

The intake of antibiotic by infected macrophages depends on concentration and size of delivery vehicles and 

the amount of macrophages present at the site of infection.   

 Vaccination Vehicles:  

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The large surface area of nanoparticles can be used for the killing of bacteria and also capturing bacterial 

toxins. A simple solution for the removal of active toxins is to use nanosponges and erythrocyte membrane 

coated polymer nanoparticles. Gold nanoparticles have adjuvant activities and can be used for the development 

of antibacterial vaccines. Gold nanoparticles also have the ability to distribute bacterial antigens.   

However, now a days such investigations can be conducted by using cheaper biodegradable polymer 

nanoparticles. Adjuvants can be used incorporation with polymer nanoparticle. Such ways have proven 

successful in the treatment TB. BCG vaccination is also used for TB and anti-TB protectin is inferior to 

BCG.166 A single dose of antigen vaccine is not sufficient for the treatment of TB. For example, there are three 

mycobacterial antigens which are Ag85B, MPT-64 and MPT-83 were placed onto PLGA nanoparticles and 

then introduced into mice through injection. After this injection the increased humoral and cellular responses 

were produced.   

Conclusion:  

This review article is aimed to provide detailed study on the role of nanoparticles in the efficacy of antibiotics. 

As bacteria are widely available on earth and they are available in different life forms. Bacterial population is 

important for our survival as they are involved in many processes and at the same time they are lethal for us 

as they can cause harm to us by causing many diseases. For centuries, thousands of humans have been died 

due to epidemics.   

Than studies lead to the discovery of antibiotics and first antibiotic was discovered by Alexender Fleming 

known as Penicillin. The antibiotics saved human life for many years but due to increased and repeated use of 

antibiotics the bacteria developed resistance towards these antibiotics. In the treatment of bacterial diseases 

the antibiotics are of no more use as bacteria are tolerant towards several antibiotics.  

In this situation when bacterial diseases are common and their sole treatment antibiotics are not effective than 

we require an alternative and the revolution in this aspect is nanoparticles. The nanoparticles are small metal 

particles that are tested to be effective in the treatment of many microbial infections. We have provided 

detailed study on the use of nanoparticles in the efficacy of nanoparticles and in future these nanoparticles will 

serve more functions and their efficiency will be enhanced soon.  

 Data Availability:  

The data that is used in this review article is provided by the relevant authors on request.  

References  

Lin, J.; Nishino, K.; Roberts, M. C.; Tolmasky, M.; Aminov, R. I.; Zhang, L.: Mechanisms of antibiotic 

resistance.  Frontiers in Microbiology 2015, 6.  

Semenitz, E.: [Mechanism of action of beta-lactam antibiotics and problems concerning the development of 

resistance in antibacterial chemotherapy]. Wiener klinische Wochenschrift. Supplementum1982, 142, 

7-11.  

Owens, R. C.; Lautenbach, E.Antimicrobial resistance: problem pathogens and clinical countermeasures; CRC 

Press, 2007.  

 Kohanski, M. A.; Dwyer, D. J.; Collins, J. J.: How antibiotics kill bacteria: from targets to networks. Nature 

Reviews Microbiology 2010, 8, 423-435.  

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