Hello Dear

The four main mechanisms by which microorganisms exhibit resistance to antimicrobials are:

Drug inactivation or modification: for example, enzymatic deactivation of penicillinG in some penicillin-resistant bacteria through the production of β-lactamases. Most commonly, the protective enzymes produced by the bacterial cell will add an acetyl or phosphate group to a specific site on the antibiotic, which will reduce its ability to bind to the bacterial ribosomes and disrupt protein synthesis.[128]

Alteration of target site: for example, alteration of PBP—the binding target site of penicillins—in MRSA and other penicillin-resistant bacteria. Another protective mechanism found among bacterial species is ribosomal protection proteins. These proteins protect the bacterial cell from antibiotics that target the cell’s ribosomes to inhibit protein synthesis. The mechanism involves the binding of the ribosomal protection proteins to the ribosomes of the bacterial cell, which in turn changes its conformational shape. This allows the ribosomes to continue synthesizing proteins essential to the cell while preventing antibiotics from binding to the ribosome to inhibit protein synthesis.

Alteration of metabolic pathway: for example, some sulfonamide-resistant bacteria do not require para-aminobenzoic acid (PABA), an important precursor for the synthesis of folic acid and nucleic acids in bacteria inhibited by sulfonamides, instead, like mammalian cells, they turn to using preformed folic acid.

Reduced drug accumulation: by decreasing drug permeability or increasing active efflux(pumping out) of the drugs across the cell surface[129] These specialized pumps can be found within the cellular membrane of certain bacterial species and are used to pump antibiotics out of the cell before they are able to do any damage. These efflux pumps are often activated by a specific substrate associated with an antibiotic.

Antibiotic resistance can be a result of horizontal gene transfer,[131] and also of unlinked point mutations in the pathogen genome at a rate of about 1 in 108 per chromosomal replication. Mutations are rare but the fact that bacteria reproduce at such a high rate allows for the effect to be significant. A mutation may produce a change in the binding site of the antibiotic, which may allow the site to continue proper functioning in the presence of the antibiotic or prevent the binding of the antibiotic to the site altogether. Research has shown the bacterial protein LexA may play a key role in the acquisition of bacterial mutations giving resistance to quinolones and rifampicin. DNA damage induces the SOS gene repressor LexA to undergo autoproteolytic activity. This includes the transcription of genes encoding Pol II, Pol IV, and Pol V, which are three nonessential DNA polymerases that are required for mutation in response to DNA damage.

Please see also

Arias CA, Murray BE (2009). "Antibiotic-Resistant Bugs in the 21st Century — A Clinical Super-Challenge". New England Journal of Medicine. 360 (5): 439–443. doi:10.1056/NEJMp0804651. PMID 19179312.

Goossens H, Ferech M, Vander Stichele R, Elseviers M (2005). Esac Project. "Outpatient antibiotic use in Europe and association with resistance: a cross-national database study". Lancet. Group Esac Project. 365 (9459): 579–87. doi:10.1016/S0140-6736(05)17907-0. PMID 15708101.

Hawkey, PM; Jones, AM (September 2009). "The changing epidemiology of resistance". The Journal of antimicrobial chemotherapy. 64 Suppl 1: i3–10. doi:10.1093/jac/dkp256. PMID 19675017.

Soulsby EJ (2005). "Resistance to antimicrobials in humans and animals: Overusing antibiotics is not the only cause and reducing use is not the only solution". British Medical Journal. 331 (7527): 1219–20. doi:10.1136/bmj.331.7527.1219. PMC 1289307free to read. PMID 16308360.

"Alternatives to Antibiotics Reduce Animal Disease". Commonwealth Scientific and Industrial Research Organization. 9 Jan 2006

Hello Dear

The four main mechanisms by which microorganisms exhibit resistance to antimicrobials are:

Drug inactivation or modification: for example, enzymatic deactivation of penicillinG in some penicillin-resistant bacteria through the production of β-lactamases. Most commonly, the protective enzymes produced by the bacterial cell will add an acetyl or phosphate group to a specific site on the antibiotic, which will reduce its ability to bind to the bacterial ribosomes and disrupt protein synthesis.[128]

Alteration of target site: for example, alteration of PBP—the binding target site of penicillins—in MRSA and other penicillin-resistant bacteria. Another protective mechanism found among bacterial species is ribosomal protection proteins. These proteins protect the bacterial cell from antibiotics that target the cell’s ribosomes to inhibit protein synthesis. The mechanism involves the binding of the ribosomal protection proteins to the ribosomes of the bacterial cell, which in turn changes its conformational shape. This allows the ribosomes to continue synthesizing proteins essential to the cell while preventing antibiotics from binding to the ribosome to inhibit protein synthesis.

Alteration of metabolic pathway: for example, some sulfonamide-resistant bacteria do not require para-aminobenzoic acid (PABA), an important precursor for the synthesis of folic acid and nucleic acids in bacteria inhibited by sulfonamides, instead, like mammalian cells, they turn to using preformed folic acid.

Reduced drug accumulation: by decreasing drug permeability or increasing active efflux(pumping out) of the drugs across the cell surface[129] These specialized pumps can be found within the cellular membrane of certain bacterial species and are used to pump antibiotics out of the cell before they are able to do any damage. These efflux pumps are often activated by a specific substrate associated with an antibiotic.

Antibiotic resistance can be a result of horizontal gene transfer,[131] and also of unlinked point mutations in the pathogen genome at a rate of about 1 in 108 per chromosomal replication. Mutations are rare but the fact that bacteria reproduce at such a high rate allows for the effect to be significant. A mutation may produce a change in the binding site of the antibiotic, which may allow the site to continue proper functioning in the presence of the antibiotic or prevent the binding of the antibiotic to the site altogether. Research has shown the bacterial protein LexA may play a key role in the acquisition of bacterial mutations giving resistance to quinolones and rifampicin. DNA damage induces the SOS gene repressor LexA to undergo autoproteolytic activity. This includes the transcription of genes encoding Pol II, Pol IV, and Pol V, which are three nonessential DNA polymerases that are required for mutation in response to DNA damage.

Please see also

Arias CA, Murray BE (2009). "Antibiotic-Resistant Bugs in the 21st Century — A Clinical Super-Challenge". New England Journal of Medicine. 360 (5): 439–443. doi:10.1056/NEJMp0804651. PMID 19179312.

Goossens H, Ferech M, Vander Stichele R, Elseviers M (2005). Esac Project. "Outpatient antibiotic use in Europe and association with resistance: a cross-national database study". Lancet. Group Esac Project. 365 (9459): 579–87. doi:10.1016/S0140-6736(05)17907-0. PMID 15708101.

Hawkey, PM; Jones, AM (September 2009). "The changing epidemiology of resistance". The Journal of antimicrobial chemotherapy. 64 Suppl 1: i3–10. doi:10.1093/jac/dkp256. PMID 19675017.

Soulsby EJ (2005). "Resistance to antimicrobials in humans and animals: Overusing antibiotics is not the only cause and reducing use is not the only solution". British Medical Journal. 331 (7527): 1219–20. doi:10.1136/bmj.331.7527.1219. PMC 1289307free to read. PMID 16308360.

"Alternatives to Antibiotics Reduce Animal Disease". Commonwealth Scientific and Industrial Research Organization. 9 Jan 2006

"Research" is an interesting concept! 

Dear Büşra Aktaş

Pls. find the attached files

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202223/

http://jb.asm.org/content/181/2/618.full

http://science.sciencemag.org/content/321/5887/365

https://ardb.cbcb.umd.edu/

http://jac.oxfordjournals.org/content/50/suppl_3/1.full.pdf

http://broom02.revolvy.com/main/index.php?s=Plasmid%20vector&item_type=topic

https://www.researchgate.net/profile/Dieter_Adam/publication/11298181_Global_antibiotic_resistance_in_Streptococcus_pneumoniae/links/540ef6e30cf2f2b29a3d1142.pdf

http://www.euroformhealthcare.biz/antibiotic-resistance.html

https://ardb.cbcb.umd.edu/tutorial.shtml

http://emerald.tufts.edu/med/apua/about_issue/about_antibioticres.shtml

http://aac.asm.org/content/57/7/3348.full

https://en.wikipedia.org/wiki/Antimicrobial_resistance

http://www.livescience.com/45446-antibiotic-resistance-genes-everywhere.html

http://learn.genetics.utah.edu/content/microbiome/resistance/

Hoping this will be helpful            

Regards

Prof. Houda Kawas

Article Global antibiotic resistance in Streptococcus pneumoniae

Dear Busra

Antibiotic resistance can be classified using database sources as:

You can find more informations in the following publication:

-Molecular sequence data in the CARD

-The Antibiotic Resistance Ontology

-Horizontal gene transfer and pathogen diversity

-Integration with NCBI, PDB, and other resources

-Integration with NCBI, PDB, and other resources

The Comprehensive Antibiotic Resistance Database. Andrew et al. Antimicrob Agents Chemother. 2013 Jul; 57(7): 3348–3357.

Find some review details:

Antibiotic resistance is an increasing crisis as both the range of microbial antibiotic resistance in clinical settings expands and the pipeline for development of new antibiotics contracts (1). This problem is compounded by the global genomic scope of the antibiotic resistome, such that antibiotic resistance spans a continuum from genes in pathogens found in the clinic to those of benign environmental microbes along with their proto-resistance gene progenitors (2, 3). The recent emergence of New Delhi metallo-ß-lactamase (NDM-1) in Gram-negative organisms (4), which can hydrolyze all β-lactams with the exception of monobactams, illustrates the capacity of new antibiotic resistance genes to emerge rapidly from as-yet-undetermined reservoirs. Surveys of genes originating from both clinical and environmental sources (microbes and metagenomes) will provide increasing insight into these reservoirs and offer predictive capacity for the emergence and epidemiology of antibiotic resistance.

The increasing opportunity to prepare a broader and comprehensive antibiotic resistance gene census is facilitated by the power and falling costs of next-generation DNA sequencing. For example, whole-genome sequencing (WGS) is being increasingly used to examine new antibiotic-resistant isolates discovered in clinical settings (5). Additionally, culture-independent metagenomic surveys are adding tremendously to the pool of known genes and their distribution outside clinical settings (6, 7). These approaches have the advantage of providing a rapid survey of the antibiotic resistome of new strains, the discovery of newly emergent antibiotic resistance genes, the epidemiology of antibiotic resistance genes, and the horizontal gene transfer (HGT) of known antibiotic resistance genes through plasmids and transposable elements. However, despite the existence of tools for general annotation of prokaryotic genomes (see, e.g., reference8), prediction of an antibiotic resistance phenotype from a genome sequence is not straightforward and, to date, computational tools for comprehensive prediction of antibiotic resistance genes within genomes have been lacking.

The proliferation of genetic and biochemical information on antibiotic resistance is resulting in a massive increase in molecular information that will facilitate our understanding of the evaluation, spread, and mechanism of antibiotic resistance. However, mining of this information is greatly hampered by the lack of a database that can unify information in a fashion that enables the gathering of over 5 decades of literature and data and includes up-to-date entry of new antibiotic resistance elements and curation of known and new genes. Such databases are increasingly common in other areas of biology and medicine, for example, InnateDB for innate immunity interactions and pathways (http://innatedb.ca/) (9). There have been efforts to establish such knowledge resources in the area of antibiotic resistance: for example, the Lahey clinic database on Ser β-lactamases (www.lahey.org/studies/), the Repository of Antibiotic Resistance Cassettes (http://www2.chi.unsw.edu.au:8080/rac/) (10) that lists a number of antibiotic resistance elements and provides some automatic annotation, the Resistance Map (http://www.cddep.org/resistancemap/) that offers an interactive format to view antibiotic resistance surveillance data, and the Antibiotic Resistance Genes Database (http://ardb.cbcb.umd.edu/) (11). These databases have proven too narrow in scope, are not regularly updated, or offer limited resources and data to integrate molecular information from genes and their products, antibiotics, and the associated literature.

Cordialy

Marius