INTRODUCTION subgroup of beta-lactam antibiotic by various

INTRODUCTION

Utilization of drugs is conspicuous for the treatment against pathogenic strains of bacteria, viruses, parasites. But this wide application of drugs, chemicals and plant extracts on these pathogens makes them more drug-resistant, this phenomenon is called “Selection Pressure”.

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There are various species of Acinetobacter which can cause different life-threatening diseases, but A. baumannii is responsible for about 80 percent of reported Acinetobacter infections and also been reported to be a cause of up to 10% of hospital-acquired (nosocomial) infections and 8.4% of hospital-acquired pneumonia(Hidron, Edwards et al. 2008, Kallen, Hidron et al. 2010)

 

In recent time many pathogens have developed resistant against most of the combinatorial drugs being used. One of them is Acinetobacter baumannii which is resistant towards carbapenem, (Su, Wang et al. 2012) a subgroup of beta-lactam antibiotic by various mechanism which includes the recruitment of new beta-lactamases or modifications to the specifications of existing enzymes, changes in outer membrane protein(OMP ex. Porin), Aminoglycoside-modifying enzymes (AMEs), Quinolone resistance(Bonomo and Szabo 2006), permeability due to the reduced content of specific protein channels such as OprD, increased expression of efflux pumps, and modifications in the contents of penicillin-binding proteins(PBPs) (Vashist, Tiwari et al. 2011), which shows bactericidal activity by  inhibiting cell wall synthesis(Nikolaidis, Favini-Stabile et al. 2014).

Acinetobacter baumannii is a short, gram-negative coccobacillus which is aerobic, immotile pathogenic microscopic organisms. Basically, it is an opportunistic pathogen, which causes pneumonia, respiratory and urinary tract infections reside on hospital surfaces and this turned into a reason for its outbreak in immunocompromised patients (Sievert, Ricks et al. 2013, Weiner, Webb et al. 2016). Acinetobacter baumannii has been distinguished as an ESKAPE pathogen (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), a group of pathogenic bacteria with a high rate of drug-resistant to are a large number of hospital-derived (nosocomial) diseases (Mari-Almirall, Cosgaya et al. 2017). So new antibiotics or antimicrobial drugs or vectors must be used to eliminate these pathogens.

In recent years the use of Nano particles for executing resistant pathogenic strain has been increased. Easy drug delivery, antimicrobial and antibacterial activity, anti-cancerous activity has increased its uses moreover. AgNPs shows their antimicrobial activity through multifarious mechanisms, AgNPs adhesion to bacterial cells, penetration inside the cells, ROS and free radical generation, and conduction of microbial signal transduction pathways have been identified as the most prominent modes of antibacterial action.

A wide range of Nano-particles, which are being used to diagnose disease accurately, sensing technologies, drug delivery, to short-out the complicated problems in oral absorption of proteins and peptides. Silver NPs is one of them and it  have a potential antimicrobial activity (Wong and Liu 2010) against Gram-negative and Gram-positive bacteria, due to their small size and the large surface area which enables them to produce multivalent interaction and results in arising high synergy.

Despite silver, the milk also has some antimicrobial activity and pathogen killing substances which are still unknown that how they function. So, use of milk proteins as a capping of AgNPs can be a great combination to use against drug-resistant Acinetobacter baumannii.

Milk contains various carbohydrates, vitamins, minerals, lipids and  protective proteins like lactoferrin, lactoperoxidase, N-acetyl-§-glucosaminidase (NAGase), PGRP, Immunoglobulins, and lysozyme which have antibacterial, antiviral, antifungal and antiparasitic activity, immunological properties, and anti-cancerous activity (Abrhaley and Leta 2018).

We hereby intend to study the role of proteins of camel, sheep, goat, cow, buffalo milk capped with silver Nano particles in inhibiting the pathogenic and resistant strain of Acinetobacter baumannii.

 

 

 

 

 

 

REVIEW OF LITERATURE

History of acinetobactor baumannii

 

 

 

 

 

 

Acinetobacter genus

Acinetobacter is a genus which includes gram negative bacteria belongs to class Gammaproteobacteria, consists more than 50 different species of bacteria from which most of them are non-pathogenic, some of them are opportunistic human pathogens. Acinetobacter are aerobic, immobile, nonfermentive, oxidase-negative species. Acinetobacter spp. are the only members of the Moraxellaceae which lacks cytochrome c oxidases.

Yet again most clinically relevant members of Acinetobacter genes come under Acinetobacter calcoaceticus–baumannii (Acb) complex. The Acb complex consists of five pathogenic species: A. baumannii, Acinetobacter nosocomialis, Acinetobacter pittii, Acinetobacter seifertii and Acinetobacter dijkshoorniae, and also one nonpathogenic species, Acinetobacter calcoaceticus (Eliopoulos, Maragakis et al. 2008).

We can identify acinetobactor spp. Separately by citrate test and urease test.

Here is the taxonomical classification of Acinetobacter baumannii

Domain:          Bacteria

Kingdom:        Eubacteria

Phylum:           Proteobacteria

Class:               Gammaproteobacteria

Order:              Pseudomonadales

Family:            Moraxellaceae

Genus:             Acinetobacter

Species:           A. baumannii (Bouvet and Grimont 1986)

ANTIMICROBIAL RESISTANT TOWARDS CARBAPENEM

In 1929 the first antibiotic penicillin was discovered to use against the threat of infectious diseases being widely spread. Then after this many more drugs came in existence. But with the increasing selection pressure, less complexity of genome (plasticity of genome), fast replication and high adaption rate made these pathogens mainly bacteria and viruses resistant to nearly any drug molecule build for them.

In recent research towards the resistant strains of most pathogenic bacteria (Acinetobactor baumanii, Enterobacteriaceae, Pseudomonas aeruginosa) whom the WHO has announced as the most critical priority for development of new antibiotics, the use of antiprotozoal drug pentamidine along with some antibiotics. It disrupts the cell surface of gram negative bacteria(Stokes, MacNair et al. 2017).

Acinetobacter baumannii is a

The mechanism of resistance of bacteria towards various drugs can be defined on the basis of the target of drug inside bacteria or microbes, mainly

1. Inhibition of the cell wall synthesis

2. Inhibition of folate metabolism

3. Inhibition of cell membrane function

4. Inhibition of nucleic acid synthesis

 

 

 

Group of antimicrobial Agent

Effect on Bacteria  

Mode of action in general

 

 

 

 

 

Pencillins

Bactericidal

Inhibition of cell wall synthesis

 

Cephalosporins

Bactericidal

Inhibition of cell wall synthesis

 

Carbapenem

Bactericidal

Inhibition of cell wall synthesis

 

Polypeptide antibiotics

Bactericidal

Inhibition of cell wall synthesis

 

Quinolones

Bactericidal

Inhibition DNA synthesis

 

 

 

 

 

Metronidazole

Bactericidal

Inhibition DNA synthesis

 

 

 

 

 

Rifamycins

Bactericidal

Inhibitions of RNA transcription

 

Lincosamide

Bactericidal

Inhibitions of protein synthesis

 

Aminoglycosides

Bactericidal

Inhibitions of protein synthesis

 

Macrolides

Bacteriostatic

Inhibitions of protein synthesis

 

Tetracyclines

Bacteriostatic

Inhibitions of protein synthesis

 

Choramphenicol

Bacteriostatic

Inhibitions of protein synthesis

 

Sulfonamides

Bacteriostatic

Competitive Inhibition

 

 

 

 

Nanoparticles

Nanoparticles are the solid particles whose size ranges from 1 to100nm. These are used as The drugs carriers, drugs are being enclosed inside the  nanoparticle or attached to its outer surface. After reaching to their target site target site, the drug payload may be released from the nanoparticle by diffusion, swelling, erosion or degradation. Active systems are also possible, e.g. drug release in response to the input of external energy such as targeted ultrasound, light or magnetic field

Silver is normally used in its nitrate form to induce antimicrobial activity, but now a days AgNPs are used, there is a great enhancement in the effective surface area available for the bacteria to be exposed to.

Whole milk contains vitamins (mainly thiamine, riboflavin, niacin, pantothenic acid, folic acid, biotin, vitamins A, B6, B12, C, D, and K), minerals (calcium, potassium, magnesium, sodium, phosphorus, and trace metals like zinc, iron, copper, manganese, iodine, selenium.), proteins (almost all amino acids but some limiting amino acids are there also like in camel milk (lysine) and cow and buffalo milk(cysteine, methionine), carbohydrates (chiefly lactose), and lipids (fats). The only important elements in which milk is seriously deficient are iron and Vitamin C (Bar?owska, Szwajkowska et al. 2011) The antimicrobial activity of milk is due to lysozymes, lactoferrin, lactoperoxidase system. In some animal like goat milk have been found to have significant amount of folate binding protein also.