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Clinical Research in Animal Science

Green Nano-therapeutics as an Alternative to Conventional Strategies for Combating Multi-drug Resistant Bacteria

Priya Verma1,2, Navinit Kumar1,2, Pallavi Shukla1,2, Ashutosh Tripathi1,2, Ved Prakash Giri1, Shipra Pandey1,2 and Aradhana Mishra1,2*

1Division of Microbial Technology, CSIR- National Botanical Research Institute, India

2Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India

*Corresponding author: Aradhana Mishra, Principal Scientist, Division of Microbial Technology, CSIR-National Botanical Research Institute, Rana Pratap Marg, India

Submission: March 23, 2022;Published: May 03, 2022

Volume2 Issue1
May, 2022

Abstract

The increasing threat of infection caused by multi-drug resistant bacteria is a global health concern that has become a serious medical emergence due to the rapid use of novel class antibiotics for curing infections. Nanotechnology introduces innovative strategies for addressing this challenge. This article concluded the recent development in the nanotechnology field and approaches for combating drug resistance in bacteria. It includes the development of nanomaterials that directly target the resistance mechanisms such as the production of reactive oxygen species or indirectly target the resistance by interfering with cellular metabolism. Nanotechnology may emerge as a potential remedy to cure MDR bacteria.

Introduction

Multi-drug resistance in bacterial strains is genetically conferred and transferred to other strains through acquisition of plasmid by horizontal gene transfer [1]. The drug resistance in bacteria is due to the low permeability of the outer membrane, efflux pumps, and synthesis of antibiotic degrading enzymes as well as modification of targets. The exaggerated use of antibiotics for treating the infectious diseases, use of multiple-broad spectrum drugs and scarcity of novel antimicrobial agents are the key factors for the spread of multi-drug resistance (MDR) species [2].

In spite of advance antimicrobial therapies, antibiotic resistance becomes life threatening, especially in immuno-compromised hosts [3]. Among most challenging MDR infections, approx 50% due to the methicillin-resistant Staphylococcal infections and 30% due to the Vancomycin Resistant Enterococci (VRE) have been reported [4-6]. These MDR bacteria causes nosocomial infections leads to prolonged hospitalization and can be life threatening [7]. In multi-drug resistant bacterial infections, gram-negative pathogens can cause high mortality rates and leave very few effective antimicrobial options [3]. Gram-negative bacteria contain a unique component on their outer membrane like lipopolysaccharide (LPS), several proteins and phospholipids which act as a permeability barrier for excluding the various drugs and antibiotics from entering the cell. The LPS itself is toxic and categorized as an endotoxin that induces a strong immune response when bacterial infection occurs in animals [8].

Thereby we need development of novel drugs and antimicrobial strategies for combating multi drug resistant bacteria. Nano-therapeutics may confer as key factor for overcoming the bacterial resistance as nanomaterials and have desirable physicochemical properties that can induce a new line of defense against MDR microorganisms [9]. Nanoparticles have large surface area so they can directly contact with cell membrane and efficiently penetrate the biofilm [10]. Apart from this, nanomaterials can increase the intracellular accumulation of the drugs and effectively prevent the transporter activity [11].

Green nano-therapeutics/nano-antibiotics as an alternative technology for combating the drug resistant bacteria

Nanoparticles can be synthesized through several methods such as chemical, physical and biological approaches. Chemically synthesized nanoparticles exert non-eco-friendly by-products that are toxic to cells. So, an increasing demand for eco-friendly, nontoxic approaches for nanomaterial synthesis which excludes use of toxic chemicals as by products. Biological moieties represents high antimicrobial activity which can reduce and stabilize the metal ions to produce nanoparticles capped with antimicrobial compounds, therefore particles also can improve the antagonistic potential in cost-efficient and eco-friendly manner [12] Coupling of nanoparticles with herbal antimicrobials are one of the less toxic and more-effective strategy to combat multi-drug resistant bacteria by inhibiting efflux pumps, biofilm formation, interference of quorum sensing in bacteria. Nano-scale materials can be used as antimicrobial agents or novel drug delivery carriers [13]. Kumari et al. [14] biosynthesized silver nanoparticles of different dimensions such as spherical, rectangular, penta and hexagonal in an ecofriendly manner through biocontrol agent Trichoderma viride, they have also performed the shape and size dependent antimicrobial activity of nanoparticles. Authors are concluded that spherical nanoparticles of 2-5nm showed excellent synergistic antimicrobial activity with antibiotics against MDR pathogens i.e., Shigella sonnei, E.coli, Serratia marcescens, Staphylococcus aureus and Pseudomonas aeruginosa. Similarly, Giri et al. [15] formulated a Biogenic Silver Nanoparticles (BSNP) based ointment and evaluated its activity against wound-infection caused by MDR bacteria S. aureus, P. aeruginosa and E. coli. They found that BSNP based ointment efficiently accelerate the wound healing activity than conventional wound healer.

Besides, nano-emulsification of essential oil can be one of the effective strategies for synthesizing potent herbal formulations against MDR bacteria. Essential oil-based nano emulsions are an emerging alternative antimicrobial compound for controlling MDR pathogens. Nano emulsion synthesized from Thymus daenensis essential oil showed an excellent antibacterial and anti-biofilm activity against MDR bacteria Acinetobacter baumannii [16]. Similarly, Cleome viscose essential oil nano emulsion has synthesized by Krishnamoorthy et al. [17] and showed drastic inhibition of several MDR bacteria by blocking the drug efflux mechanism of methicillin-resistant S. aureus (MRSA), Drug resistant (DR) Streptococcus pyogenes, and DR extended spectrum beta-lactamase (ESBL)-producing E. coli, K. pneumoniae, and P. aeruginosa. They reported that nanoemulsion disrupts the functional group of lipids, proteins and nucleic acid, leading to damage of the cell membrane and walls of drug resistant bacteria. Moreover, the bioactive phytochemicals present in the nanoemulsion inhibit the drug efflux mechanism and metabolic enzymes in MDR pathogens. Four mechanisms of antibacterial activity have been hypothesized which are as follows:
A. The accumulation of nanomaterial in the bacterial membrane affects the permeability which leads to release of intracellular biomolecules and also disrupts the proton motive force of the plasma membrane.
B. Nanoparticles produce reactive oxygen species (ROS) in the cell which leads to oxidative damage of cellular structures.
C. Absorption of nanomaterials by the cells, leading to subsequent reduction of intracellular ATP production and it also leads to DNA damage of MDR bacteria.
D. Binding of nanoparticles and its active ions with different enzymes causing arrest of cellular respiration.

The generation of reactive oxygen species, inactivation of cellular enzymes, disruption of cellular membrane, and DNA damage are some mechanisms of nanomaterials which leads to cell lysis and death of MDR bacteria [18-22].

Conclusion

The widely spread threat of multi-drug resistance create immense pressure on pharmaceutical sector to search for novel antimicrobial agents. In a battle against MDR bacteria, nanotechnology has a potential to change the conditions and prevent the spread of drug resistance. Importantly, green metallic nanoparticles as well as essential oil nano emulsions are ecofriendly, cost-effective, and known to be efficient antimicrobial agents against MDR bacteria. The article showcased the emergence of multi-drug resistance in bacteria and role of nano-therapeutics against MDR bacteria. Further work is still required in order to elucidate the whole mechanism to action of nanomaterials and toxicity of nanomaterials in humans.

References

  1. Hiramatsu K, Cui L, Kuroda M, Ito T (2001) The emergence and evolution of methicillin-resistant Staphylococcus aureus. Trends Microbiol 9(10): 486-493.
  2. Du W, Chen H, Xiao S, Tang W, Shi G (2017) New insight on antimicrobial therapy adjustment strategies for gram-negative bacterial infection: A cohort study. Medicine 96(13): e6439.
  3. Bassetti M, Righi E (2013) Multidrug-resistant bacteria: what is the threat? Hematology Am Soc Hematol Educ Program 2013: 428-432.
  4. Satlin MJ, Calfee DP, Chen L, Fauntleroy KA, Wilson SJ, et al. (2013) Emergence of carbapenem-resistant Enterobacteriaceae as causes of bloodstream infections in patients with hematologic malignancies. Leuk Lymphoma 54(4): 799-806.
  5. Quilty S, Kwok G, Hajkowicz K, Currie B (2009) High incidence of methicillin‐resistant Staphylococcus aureus sepsis and death in patients with febrile neutropenia at Royal Darwin Hospital. Intern Med J 39(8): 557-559.
  6. Bow EJ (2013) There should be no ESKAPE for febrile neutropenic cancer patients: the dearth of effective antibacterial drugs threatens anticancer efficacy. J Antimicrob Chemother 68(3): 492-495.
  7. Vivas R, Barbosa AAT, Dolabela SS, Jain S (2019) Multidrug-resistant bacteria and alternative methods to control them: an overview. Microb Drug Resistance 25(6): 890-908.
  8. Exner M, Bhattacharya S, Christiansen B, Gebel J, Goroncy Bermes P, et al. (2017) Antibiotic resistance: What is so special about multidrug-resistant Gram-negative bacteria? GMS Hyg Infect Control 12: Doc05.
  9. Singh R, Smitha MS, Singh SP (2014) The role of nanotechnology in combating multi-drug resistant bacteria. J Nanosci Nanotechnol 14(7): 4745-4756.
  10. Al Fahad AJ, Aldossary AM, Alshehri AA, Alomary MN, Almughem FA, et al. (2021) Microbial nanotechnology in treating multidrug-resistance pathogens. Microbial Nanotechnology: Green Synthesis and Applications pp: 191-216.
  11. Lei Z, Karim A (2021) The challenges and applications of nanotechnology against bacterial resistance. J Vet Pharmacol Therapeutics 44(3): 281-297.
  12. Kumari M, Pandey S, Giri VP, Bhattacharya A, Shukla R, et al. (2017) Tailoring shape and size of biogenic silver nanoparticles to enhance antimicrobial efficacy against MDR bacteria. Microb Pathog 105: 346-355.
  13. Baptista PV, McCusker MP, Carvalho A, Ferreira DA, Mohan NM, et al. (2018) Nano-strategies to fight multidrug resistant bacteria- “A Battle of the Titans”. Front Microbiol 9: 1441.
  14. Kumari M, Shukla S, Pandey S, Giri VP, Bhatia A, et al. (2017) Enhanced cellular internalization: a bactericidal mechanism more relative to biogenic nanoparticles than chemical counterparts. ACS Appl Mater Interfaces 9(5): 4519-4533.
  15. Giri VP, Pandey S, Kumari M, Paswan SK, Tripathi A, et al. (2019) Biogenic silver nanoparticles as a more efficient contrivance for wound healing acceleration than common antiseptic medicine. FEMS Microbiol Lett 366(16): fnz201.
  16. Moghimi R, Aliahmadi A, Rafati H, Abtahi HR, Amini S, et al. (2018) Antibacterial and anti-biofilm activity of nanoemulsion of Thymus daenensis oil against multi-drug resistant Acinetobacter baumannii. Journal of Molecular Liquids 265: 765-770.
  17. Krishnamoorthy R, Athinarayanan J, Periasamy VS, Adisa AR, Al Shuniaber MA, et al. (2018) Antimicrobial activity of nanoemulsion on drug-resistant bacterial pathogens. Microbial Pathogenesis 120: 85-96.
  18. Das B, Dash SK, Mandal D, Ghosh T, Chattopadhyay S, et al. (2017) Green synthesized silver nanoparticles destroy multidrug resistant bacteria via reactive oxygen species mediated membrane damage. Arabian Journal of Chemistry 10(6): 862-876.
  19. Morones JR, Elechiguerra JL, Camacho A, Holt K, Kouri JB, et al. (2005) The bactericidal effect of silver nanoparticles. Nanotechnology 16(10): 2346-2353.
  20. Rai M, Yadav A, Gade A (2009) Silver nanoparticles as a new generation of antimicrobials. Biotechnol Adv 27(1): 76-83.
  21. Raffi M, Hussain F, Bhatti TM, Akhter JI, Hameed A, et al. (2008) Antibacterial characterization of silver nanoparticles against coli ATCC-15224. J Mater Sci Technol 24(2): 192-196.
  22. Rolston KV (2005) Challenges in the treatment of infections caused by gram-positive and gram-negative bacteria in patients with cancer and neutropenia. Clin Infect Dis 40(Suppl 4): S246-S252.

© 2022 Aradhana Mishra. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and build upon your work non-commercially.