Tuesday, 30 December 2014

Synthetic DNA and artificial cell  what are the ethical issues its application in the real life and in human disease at cost of 400 million dollars Research"

Authors are
o*Professor Pranab Kumar Bhattacharya MD(cal univ) FIC path(Ind),Professor Dept of pathology
*Rupak Bhattacharya Bsc(cal.univ )MSc(JU), **Ritwik Bhattacharya B.com(cal.Univl), **Somayak Bhattacharya BSC (HM)(IGNOU)  MSc( PUSHA) - Asst Lecturer of IHM Ahemadabad India - Residences 7/51 Purbapalli,Sodepur, Kol­110, ***Miss Upasana Bhattacharya - “  Only Daughter of Prof PK Bhattacharya  **Dalia Mukherjee BA(hons) cal Univ, Miss Oindrila Mukherjee, Miss Ayshi Mukherjee    Dr Hriday Das MD(cal.Univ ) DTM&H(cal Univ) Dr Tarun Biswas MBBS(cal Univ) Dept of Pathology
*Previously  at Institute of Post Graduate Medical Education Research 244 AJC Bose Road kol-20 West Bengal, India, Now Posted as Professor&HOD of Pathology  at Murshidabad District Medical College Behrampore Murshidabad West Bengal
Published online 24 May 2010 | Nature | doi:10.1038/news.2010.261

A synthetic creation story Claims of 'synthetic life' reflect only our changing conception of what life is and how it might be made, says Philip Ball. Philip Ball Last week's announcement of the 'chemical synthesis of a living organism' by Craig Venter and his colleagues at the J. Craig Venter Institute1heads up a very long tradition. Claims such as this have been made throughout history.That's not to cast aspersions on the new results. One can challenge the idea that Venter's bacterium stands apart from Darwinian evolution, modelled as it is on Mycoplasma mycoides.It is nonetheless an unprecedented triumph of biotechnological ingenuity.
But, set in a historical context, what the researchers have achieved is not so much a 'synthesis
of life' as a semi-synthetic recreation of what we currently deem life to be. And, as with
previous efforts, it should leave us questioning the adequacy of that view.
To see that the new results reiterate a perennial theme, consider the headline of the Boston
Herald in 1899: "Creation of Life. Lower Animals Produced by Chemical Means." The article
described how German biologist Jacques Loeb induced an unfertilized sea-urchin egg to divide
and develop into a larva by treating it with salts. Loeb went on to talk in earnest about "the artificial production of living matter", and he was not alone in blending his discovery with speculations about the de novo creation of life. In 1912, the physiologist Edward Albert Schäfer alluded optimistically to Loeb's results in his presidential address to the British Association, in which he expressed great optimism about "the possibility of the synthesis of living matter"2 .Such claims are commonly seen to imply that artificial human life is next on the agenda. It wasa sign of the times that the New York Times credulously reported in 1910 that, "Prof.Herrera, a Mexican scientist, has succeeded in forming a human embryo by chemical combination". It is surely no coincidence that many media reports have compared Venter to Frankenstein, or that the British newspaper The Observer mistakenly suggested he has"succeeded in 'creating' human life for the first time".
What is life?
Beliefs about the feasibility of making artificial organisms have always been governed by the
prevailing view of what life is. When the Universe was seen as an intrinsically fecund matrix,
25-5-2010 A synthetic creation story : Nature Ne…nature.com/…/news.2010.261.html 1/7“'Life' in biology,rather like 'force'in physics, is aterm carried over from a time when scientists thought quite differently,when it served as a makes hift bridge over the inexplicable.”permitting bees and vermin to emerge from rotten flesh by spontaneous generation, it seemed natural to imagine that sentient beings might issue forth from insensate matter. Mechanical models of biology developed during the seventeenth century fostered the idea that a 'spark of life' — after the discovery of electricity, literally that — might animate a suitably arranged assembly of organic parts. The blossoming of chemistry and evolutionary theory in the nineteenth century, meanwhile, spurred a conviction that it was all about getting the recipe right, so that nature's diverse grandeur sprung from primordial colloidal jelly called protoplasm. Yet each apparent leap forwards in this endeavor more or less coincided with a realization that the problem is not so simple. Protoplasm appeared as organic chemists were beginning to erode the concept of vital ism and to appreciate the baffling constitution of organic matter. The claims of Loeb and Schäfer came just before tools for visualizing the sub cellular world began to show the incredible complexity of life's micro structure. And it was the same story for the next big splash in 'making life', when in 1953 Harold Urey and Stanley Miller announced their celebrated 'prebiotic soup' experiment, in which they conjured amino acids from simple raw materials. Some press reports regarded this as a new genesis, in principle if not in practice. Yet that same year saw the game-changing discovery oflife's informational basis in the work of Crick and Watson. Now life was not so much about molecules, but about cracking, and perhaps then rewriting, the genetic code.No more codes Which brings us to Venter et al. Now that the field of genomics has fostered the belief that in sequencing genomes we are reading a 'book of life', it's easy to see why 'booting up' a wholly synthetic genome in a bacterial host should be popularly deemed a synthesis of life itself. Here the membranes, the cytoplasm — everything except the genes — are mere peripherals to the hard drive of life, whose algorithmic instructions need only be rejigged to produce new organisms. But this latest work should encourage us to lay aside the very concepts of an 'artificial organism'and a 'synthesis of life'. Life is not a thing one makes, nor is it even a process that arises or is set in motion. It is a property we may chooseto bestow, more or less colloquially, on certain organizations of matter.25-5-2010 A synthetic creation story : Nature News…nature.com/…/news.2010.261.html 2/7#10725
Comment  No#10725
Title­"Synthetic DNA and artificial cell – what are the ethical issues its application in the
real life and in human disease at cost of 400 million dollars Research"
Authors
o*Professor Pranab Kumar Bhattacharya MD(cal) FIC path(Ind),Professor Dept of pathology
oRupak Bhattacharya Bsc(cal)MSc(JU), Ritwik Bhattacharya B.com(cal), Somayak Bhattacharya MBA 7/51 Purbapalli,Sodepur, Kol­110, Miss Upasana Bhattacharya – daughter of Prof PK Bhattacharya Dr. Avisnata Das MBBs(cal) Dalia Mukherjee BA(hons) cal Miss Oindrila Mukherjee, Mrs Chandrani Dutta BSC(Zoology)* Dr Hriday Das MD(cal) DTM&H(cal) *Dr Tarun Biswas MBBS(cal) Dept of Pathology
*Institute of Post Graduate Medical Education Research 244a AJC Bose Road kol-20 West Bengal,
India
25-5-2010 A synthetic creation story : Nature Ne… nature.com/…/news.2010.261.html 3/7 India

Artificial life is a field of study and an associated art form which examine systems related to life, its
processes, and its evolution through simulations using computer models, robotics, and biochemistry.
There are three main kinds of artificial life named for their approaches: soft from software; hard , from hardware; and wet, from biochemistry molecules. Artificial life imitates traditional biology by trying to recreate biological phenomena. Artificial life has had a controversial history. John Maynard Smith11 criticized certain artificial life work in 1994 as "fact-free science". However, the recent publication of artificial life articles in widely read world’s top impact factor and coveted science journals such as Science and Nature is evident that artificial life techniques are becoming more accepted in the mainstream­as synthetic biology, at least as a method of studying Darwin’s Chemical evolution. Synthetic and self replicating DNA or RNA is part of such an artificial life and tool for studying evolution of life in earth. Evolving such an artificial DNA in laboratory was thus for long years before attempt of research since Watson and Crick Double Helix. The artificial DNA-like molecule directed the synthesis of copies of itself and then copies of the copies, mimicking the natural process of evolution as it was first outlined by Charles Darwin. A polynucleotide is a building block of DNA, or a "letter" in the genetic alphabet used to write the "book" describing our genetic inheritance. The first Synthetic Virus was done in 2002 in stony brook university Newyork by a team of scientist led by Eckarde wimmr (Science, 9 August 2002, p. 1016) Benner and Michael Sismour- two Graduate student of university of California in 2004 first made a synthetic DNA of 12 nucleotides of a virus but it could not however copied itself. In 2010, The first synthetic and self replicating DNA /cell as a bacterium has been claimed by Professor Dr C J Venter of J. Craig Venter Institute (JCVI) in Rockville, Maryland, and San Diego, California, [ He was best known for his work with the Human Genome Project] is successful and same is published in journal the science[ 1]. The cell is claimed totally derived from a synthetic chromosome [They bought it from a company more than 1000 -1080-base sequences that covered the whole M. mycoides genome], made with four bottles of chemicals on a chemical synthesizer, starting with information and using genetic code created by a super computer. The Venterâ team [20 members team] synthesized the largest piece of DNA so far ” a million units in length ” and in making it accurate enough to substitute for the cell  own DNA at cost of $40 million research. Venter's team said they worked with a synthetic version of the DNA from a small bacterium called Mycoplasma mycoides which was transplanted into another bacterium called Mycoplasma capricolum, which had most of its insides DNA removed. The new microbe came to life and began replicating in the lab dish. Specifically, the team showed that the artificially created DNAlike molecule containing six gene ­building nucleotides – instead of the four found in natural DNA –could support the molecular "photocopying" operation known as polymerase chain reaction. The genome Dr. Venter synthesized is copied from a natural bacterium that infects goats. 580,000 DNA units in length, of a small bacterium, Mycoplasma genitalium. His goal however was to make cells that might take carbon dioxide out of the atmosphere and produce methaneose .Replacing the genome of any bacterial cell with one from another species by transplanting a whole genome as naked DNA is however a long known method as gene cloning[3] / and or gene transfer mechanism called genome transplant. Gene cloning will result a new species[ 2] De novo synthesis of a self replicating bacterial or human DNA is here an increasingly valuable resource for a broad research and future application. Synthesis of Gene /DNA is also not new but an old concept. Synthesis of gene length (1-3Kb) DNA is however very common. The Process of Synthetic DNA construction involves the assembly of Overlapping Oligonucleotides into contiguous fragments of dsDNA using PCR based and or ligation based methods[4 ,5] or by Pair wise Selection assembly(PSA) methods for large scale long length automated synthetic DNA production more then 91Kb DNA6, where A target assembly sequence is broken down into sub-fragments that are synthesized with flanking tags .At PSA level 0, sub-fragments are inserted into one of two PSA vectors where tags activate two, diver gently oriented select-able 25-5-2010 A synthetic creation story : Nature Ne… nature.com/…/news.2010.261.html 4/markers . Level 0 sub-fragment pairs are excised so that only one activation tag is retained for each sub-fragment. Subsequent pair ligation occurs in a second PSA vector where tags activate a second set of select-able markers , producing a PSA level 1 product. This hierarchical process is repeated, switching between two vectors with different selectable markers, until the full-length product is assembled 6.Recently, recombination-based methods were also used range of applications to construct a 134-kb fragment in Bacillus subtilis and 583- Kb fragment of Saccharomyces cerevisiae Synthetic DNA (7,8 ). While synthesis of gene ­length DNA (13 kb) is common, the ability to quickly and cost effectively assemble longer-length DNA (>10 kb) remained of course a challenge. 256 orthologous
genes shared by the Gram-negative Haemophilus influenzae and the Gram-positive bacterial life
Mycoplasma genitalium genomes are a close approximation of a minimal gene set . The Mollicutes,
generically known as the mycoplasmas, are the best experimental platform for experimentally defining a minimal gene set. Mycoplasmas are obligate parasites that live in relatively unchanging nichesrequiring little adaptive capability. M. genitalium, a human urogenital pathogen, is the extreme manifestation of this genomic parsimony, having only 482 protein-coding genes and the smallest genome, at 580 kb, of any known free-living organism capable of being grown in axenic culture[9]
Mycoplasma genitalium has the smallest genome of any organism that can be grown in pure culture. It has a minimal metabolism and little genomic redundancy. Consequently, its genome is expected to be a close approximation to the minimal set of genes needed to sustain bacterial life. To construct synthetic DNA of Mycoplasma genetelium it is always very essential to identify and delete all the putative nonessential gene, isolation and characterization of trasposon mutants and mixture of mutant genes butpreservation and non-disruptions of DNA recombination & six DNA repair gene like recA,recU, DNA hellicase gene like ruvA, ruvB DNA Glycosylase gene mute M which excises oxidized purine from DNA and DNA damage inducible gene[10]In 1995, a team led by the trio Venter, Smith and Hutchison sequenced the 600,000-base chromosome of bacterium Mycoplasma genitalium, the smallest genome of a free-living organism. The microbe has about 500 genes, and researchers found they could delete100 individual genes without ill effect (Science, 14 February 2003, p. 1006) In 2007, Venter, Smith,Hutchison, and colleagues finally demonstrated that they could transplant natural chromosomes fromone microbial species to another (Science, 3 August 2007, p. 632). By 2008, they showed that theycould make an artificial chromosome that matched M. genitalium's but also contained "watermark"DNA sequences that would enable them to tell the synthetic genome from the natural one (Science, 29February 2008, p. 1215) The first Synthetic Virus was done in 2002 in stony brook university Newyork by a team of scientist led by Eckarde wimmr (Science, 9 August 2002, p. 1016)
The synthetic genome created by Venter's team is almost identical to that of a natural bacterium. It
was achieved at great expense; an estimated $40 million, and effort, 20 people working for more than
a decade. Dr. Venter took a first step toward this goal three years ago, showing that the natural DNA
from one bacterium could be inserted into another and that it would take over the host cell’s
operation. He said that before copying the DNA, he excised 14 genes likely to be pathogenic, so the
new bacterium, even if it escaped, would be unlikely to cause goats harm.Dr. Venter calls the result synthetic cell and is presenting the research as a landmark achievement that will open the way to creating useful microbes from scratch to make products like biofuels. At a press conference Thursday, Dr. Venter described the converted cell as “the first self replicating species weâve had on the planet Though the scientists claim for creation of artificial living cell “He has not created life, only mimicked it,â€what we want to say There remains much about the ethical issues to be solved
1] Consequence of progress in the new field of synthetic biology is an emerging view of cells as
assemblages of parts that can be put together to produce an organism with a desired phenotype
2].Over the long term, the approach will be used to synthesize increasingly novel designed genomes,
and may be a tool for bioterrorism and we need protections from military or terrorist misuse and
25-5-2010 A synthetic creation story :
3]. Will the newer synthetic biology help human mankind by detecting where is the defect lies the
human genome that give rise cancer or in formulation of new drug or vaccine?
4]. is it a step towards ... creation of living beings or artificial life with capacities and natures that could
never have naturally evolved."
5]. In Future Can some one will design for Human clone?
Nature Ne…nature.com/…/news.2010.261.html 5/7 comment 2010-05-25 08:14:52 AM  Posted by: Prof. Pranab Kumar Bhattacharya
References
1] Elizabeth Pennisi Synthetic Genome Brings New Life to Bacterium News of the Week Genomics:
Science 21 May 2010:Vol. 328. no. 5981, pp. 958 – 959 DOI: 10.1126/science.328.5981.958

2] R. L. Warren, J. D. Freeman, R. C. Levesque, D. E. Smailus, S. Flibotte, and R. A. Holt Transcriptionsof foreign DNA in Escherichia coli Genome Res. 18, 1798-1805. 2008

3] G. A. Benders, V. N. Noskov, E. A. Denisova, C. Lartigue, D . G. Gibson, N. AssadGarcia,
R. Y. Chuang, W. Carrera, M. Moodie, M. A. Algire, et a Cloning wholebacterial genomes in yeast. Nucleic Acids Res. 38, 2558-2569 2010

4] Tian,J., Gong,H., Sheng,N., Zhou,X., Gulari,E., Gao,X. andChurch,G. (2004) Accurate multiplex
gene synthesis fromprogrammable DNA microchips. Nature, 432, 1050–1054.

5] Mandecki,W. and Bolling,T.J. (1988) FokI method of genesynthesis. Gene, 68, 101–107.

6] *, William J. Blake Brad A. Chapman, Anuradha Zindal, Michael E. Lee, Shaun M. Lippow and BrianM. Baynes , Pair wise selection assembly for sequence-independent construction of long-length DNANucleic Acids Research, 2010, Vol. 38, No. 8P 2594–2602 Published online 1 March 2010
doi:10.1093/nar/gkq123

7] Gibson,D.G., Young,L., Chuang,R.Y., Venter,J.C.,Hutchison,C.A. III and Smith,H.O. (2009)
Enzymatic assembly ofDNA molecules up to several hundred kilo bases. Nat. Methods, 6, 343â
€“345,2009.

8] Gibson,D.G., Benders,G.A., Andrews-Pfannkoch,C.,Denisova,E.A., Baden-Tillson,H., Zaveri,J.,
Stockwell,T.B., Brownley,A., Thomas,D.W., Algire,M.A. et al Complete chemical synthesis, assembly,and cloning of a Mycoplasma genitalium genome., Science 319, 1215–1220.2008

9] Fraser, C. M., Gocayne, J. D., White, O., Adams, M. D., Clayton, R. A.,Fleischmann, R. D., Bult, C. J.,Kerlavage, A. R., Sutton, G., Kelley, J. M., et al. 1995) Science 270, 397–403.1995

10] John I. Glass, Nacyra Assad-Garcia, Nina Alperovich, Shibu Yooseph, Matthew R. Lewis, Mahir
Maruf,Clyde A. Hutchison III, Hamilton O. Smith*, and J. Craig Venter Essential genes of a minimal
bacterium, proceeding Nat Academy Science USA PNAS _ January 10, 2006 _ vol. 103 ,425-30
www.pnas.org_cgi_doi_10.1073_pnas.0510013103

11] Horgan, J. 1995. From Complexity to Perplexity. Scientific American. p107
 This comment is cited by 2
1] Synthetic Cells and Their Regulatory Challenges by J C Varela - Eur. J. Risk Reg., 2010 - Hein Online

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Monday, 15 December 2014

Emergence of antibiotic-resistant bacterial strains,methicillin-resistant Staphylococcus aureus, extendedspectrum beta lactamases, and multi-drug resistance is a problem similar to global warming



 Revista da Sociedade Brasileira de Medicina Tropical 47(6):815-816, Nov-Dec, 2014
http://www.scielo.br/pdf/rsbmt/v47n6/0037-8682-rsbmt-47-06-815.pdf                                               

 Running Title -: Bhattacharya PK – MRSA problem  is similar to global warming

Address to: Dr. Pranab Kumar Bhattacharya. Dept. of Pathology/District
Medical College. Station Road 742101 Berhampore, Murshidabad,
West Bengal, India.
Phone: 91 92 3151-0435
e-mail: profpkb@yahoo.co.in

Received 11 June 2014
Accepted 26 November 2014

Emergence of antibiotic-resistant bacterial strains,methicillin-resistant Staphylococcus aureus, extended spectrum beta lactamases, and multi-drug resistance is a problem similar to global warming
                     Pranab Kumar Bhattacharya[1]
[1]. Department of Pathology, Murshidabad District Medical College, Berhampore, Murshidabad, West Bengal, India.

Dear Editor,
I recently read the article by Porto et al. entitled Active surveillance to determine the impact of methicillin resistance on mortality in patients with bacteremia and influences of the use of antibiotics on the development of MRSA infection, published in Revista da Sociedade Brasileira de Medicina Tropical/Journal of the Brazilian Society of Tropical Medicine[1].
Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen worldwide in modern health care-associated infections. Within 1 year of introducing methicillin in clinical practice, MRSA strains were first detected in 1961 in Britain, followed by Denmark in 1963, and subsequently other parts of the world. MRSA is associated with increased morbidity and mortality from sepsis and rapidly develops multi-drug resistance (MDR). In a hospital-based study at Kolkata metro City by the author, MRSA showed in vitro drug resistance to co-trimoxazole (33%), erythromycin (75%), penicillin (22%), oxacillin (11%), ciprofloxacin (84%), mupirocin (8%), rifampicin (17%), and methicillin (85%); and MRSA also showed in vitro sensitivity to clindamycin (90%), cefotaxin (99%), vancomycin (100%) and linezolid (100%). Linezolid and vancomycin have been clinically used as reliable last resort drugs for MRSA treatment. Since 1997, vancomycin-intermediate and -resistant S. aureus and linezolid-resistant strains of S. aureus have been
reported[2,3]. Data on linezolid resistance from Asian countries, especially from the Indian subcontinent, are extremely rare, and Chakraborty et al.[4 ]found only a single case of linezolid resistant MRSA in a 33-year-old male patient with non-healing ulcers in a tertiary care medical college using polymerase chain reaction (PCR) to detect: I) mutations in the domain V region of one or more of the five copies of the 23S recombinant deoxyribonucleic acid (rDNA) gene; II) acquisition of the plasmid-mediated ribosomal methyl transferase Cfr gene, and III) deletion/mutation in the ribosomal protein L3 of peptidyl transferase center[5].
The prevalence of MRSA has increased in most private health care institutions, including Kolkata City of West Bengal, India, where it increased from 6.9% in 1988, to 54% in 2003, to 63% in 2013, varying from 8% to 71% across India[6].Resistance is due to an altered penicillin binding protein encoded by the mecA gene. MRSA can be confirmed using multiplex PCR-based detection of the mecA2 gene using the ATA3` mecA1 forward (5`GTAGAAATGACTGAACGTCCG) and reverse(5`CCATTCCACATTGTTTC) primers, as well as the oxacillin disk diffusion (ODD) and cefoxitin disk diffusion (CDD) tests.
Although considered the gold standard for MRSA diagnosis, PCR for the mecA gene is costly and requires a skilled technician; thus, many tertiary care hospitals and even medical colleges or private centers in West Bengal cannot afford to routinely perform PCR. ODD has a sensitivity of 97%, specificity of 95%, and an effectiveness of 97%; and CDD has sensitivity, specificity, and effectiveness of 100% for the diagnosis of MRSA infection when compared with PCR for mecA. In Kolkata, common causative organisms of hospital-acquired infections are Staphylococcus aureus, Streptococcus viridans, aerobic gram-negative bacilli such as Pseudomonas aeruginosa, Escherichia coli, and other MDR gram-negative organisms, including Acinobacter,
Klebsiella, E. coli, Salmonella, and extended spectrum beta lactamase (ESBL) enterobacteriaceae (E. coli and Klebsiella; prevalence,62-100%), and S. aureus, responsible for various mild to serious infections in multiple hospital units, leading to a higher median total hospital cost, longer hospital stay after infection (mean 22.9 days6), fatal sepsis, and death (mean 84%5). MRSA and methicillin-sensitive S. aureus strains with quinolone resistance have also been reported from an eye care hospital in Bhubaneswar, India7,8. Community-associated MRSA(CAMRSA) currently comprises 40-60% of all nosocomial S. aureus infections and cause sepsis at many centers worldwide, is one of the most prevalent significant pathogens, and causes a variety of infections from mild skin and soft tissue infections and necrotizing fasciitis to fatal sepsis. In one of our studies, when 336 individuals in the community were randomly screened from their deeper nasal cavity for persistence of S. auerus, the first 136 subjects showed no MRSA, whereas in the next 200 subjects, only 11%showed MRSA. In another study from Wardha, India, of 280 CAMRSA samples, 51.8% had the mecA gene[5]. CAMRSA colonizes the anterior nares, and nasal carriage of S. aureus acts as an endogenous reservoir for clinical infections in colonized individuals or as a source of cross colonization for community-based infections. Nasal S. auerus colonization is an important risk factor for life-threatening infections of the carrier. In our CAMRSA study, the overall incidence of S. aureus was 12-28%, even in healthy subjects: a higher prevalence may occur in overcrowded and slum areas.MRSA results in surgical site infection, non-healing ulcer, necrotizing fasciitis, pneumonia, urinary tract infection, and central venous catheter-associated infections. Due to use of previous third-generation antibiotics in critical care units, coagulase-negative staphylococci cause major infections, followed by Klebsiella pneumoniae, Pseudomonas aeruginosa, and non-albicans Candida -producing bio films in urinary catheters; nasogastric, parenteral nutrition, and tracheostomytubes; and mechanical ventilators. Risk factors and mortality rate are always higher with MRSA infection. Comorbid conditions that act as risk factors include cancer, heart disease, nephropathy, diabetes mellitus, chronic obstructive pulmonary disease, polytrauma, dyslipidemia, human immunodeficiency virus, cystic fibrosis, hepatitis, pulmonary emphysema, dialysis,and tobacco and marijuana smoking.
In 210 samples the neonatal intensive care unit of a tertiary care public hospital in Kolkata, the most common isolated bacteria causing sepsis (all with a high C-reactive protein value) included Klebsiella (42.3%), MRSA (32.1%), and coagulase-negative staphylococci (11.1%). Of the 44 MRSA infection cases, 2-15% showed resistance to amikacin, gentamycin, cloxacillin, ofloxacin, amoxicillin/clavulanic acid, levofloxacin, cefotaxine, and co-trimoxazole, in addition to vancomycin(100%)[ 4.]
Today, the persistent, indiscriminate, and inappropriate use of antibiotics and the increasing specter of antibiotic resistance are an emerging critical situation for healthcare. This situation needs immediate action with current anti-infective therapies in West Bengal. MDR organisms will continue to increase unless clinicians in most care hospitals and private practices improve the rational use of antibiotics. The matter is rendered increasingly complicated due to the presence of ESBL and carbapenamase-producing organisms due to the blinded use of third and fourth-generation antibiotics. The potential for misuse and abuse of antibiotics was recognized shortly after their introduction into West Bengal; this may have been further escalated by failure to obtain appropriate culture and in vitro sensitivity reports for lower respiratory and urinary tract infections and pus. Meropenem or tazobactam is routinely used as the choice first-line antibiotic in most private care hospitals and nursing homes and for some doctor’s prescriptions; this is due to kickbacks in the form of monetary commissions from pharmacy houses. We need urgent implementation of an effective antibiotic policy, and the basis of that policy rests on generating microbiological data and prescription audits through electronic prescriptions to be introduced to all public and private health care institutes(where approximately 60% of antimicrobial use is inappropriate) or at any geographical location where drug resistance has developed.
Antibiotic resistance is no less a problem than global warming. Moreover, the overuse of antibiotics causes the emergence of bacterial resistance and increases healthcare costs and sepsis-related deaths. We propose the development of a new global organization to lead the battle against antibiotic resistant
pathogens and call for this organization to be modeled on the organization created to combat global warming, the Intergovernmental Panel on Climate Change. This organization would be comprised of specialists in clinical and pathological medicine and include epidemiologists, microbiologists, pharmacologists, health economists, and international lawyers.

ACKNOWLEDGMENTS-:

The author acknowledges the following individuals for their help to carry out the work : Miss Upasana Bhattacharya,- only daughter of Prof. Dr. Pranab Kr Bhattacharya  * Mr .Rupak Bhattacharya, * Mr Ritwik Bhattacharya, * Miss Rupsa Bhattacharya, * Mr. Hindole Mukherjee, ** Mrs Dalia Mukherjee, ** Miss Oindrila Mukherjee, ** Miss Ayishi Mukherjee, *** Dr. Arya Sen and ***Prof. Pratip Kundu.
*7/51 purbapalli Sodepur Dist 24 Parganas(North) Kolkata110 ;West Bengal India ** Swamiji Nagar. South Habra, Dist 24 Pargnas(north), West Bengal, India ; *** Murshidabad District Medical college  Dept of Pathology and Dept of Microbiology

References
1. Porto JP, Santos RO, Gontijo Filho P, Ribas RM. Active surveillance to determine the impact of methicillin resistance on mortality in patients with bacteremia and influences of the use of antibiotics on the development of MRSA infection. Rev Soc Bras Med Trop 2013; 46:713-718.

2. Hiramtsu K, Hanaki H, Ino T, Yabuta K, Oguri T, Tenover FC.  Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J Antimicrob Chemother 1997; 40:135-136.

3. Centers for Disease Control and Prevention (CDC). Staphylococcus aureus resistant to vancomyci--United States, 2002. MMWR Morb Mortal Wkly Rep 2002; 51:565-567.

4. Chakraborty B, Chakraborty B, Dopthap YP, Banerjee D.  LRSA suspect, taken to molecular court, PCR trialled, proven guilty. Ann Trop Med Public Health 2013; 6:653-657.

5. Mallick S, Kumar, Basak S. Accurate detection of methicillin resistant Staphylococcus aureus in day to day practice: a great help to clinicians. J Indian Med Assoc 2011; 109:892-895.

6. Bhattacharya S. Is screening for antibiotic-resistant bacteria justified in the Indian context? Indian J Med Microbiol 2011; 29:213-217.

7. Choudhury R, PandaS, SinghDV. Emergence and disseminationof antibiotic resistance: a global problem. Indian J Med Microbiol 2012; 30:384-390.

8. Choudhury R, PandaS, Sharma S, Singh DV. Staphylococcal infection, antibiotic resistance, and theraputics. In: Pana M, editor. Antibiotic resistant bacteria- a continuous challenge in the new
millennium. Chapter 10. In Tech; 2012. p. 247-272.

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Now Posted as  Murshidabad Medical College Beharampur West Bengal , India
  Authors’ reply: Emergence of antibiotic-resistant bacterialstrains, methicillin-resistant Staphylococcus aureus andextended spectrum β-lactamases, and multi-drug resistance
are problems similar to global warming
Juliana Pena Porto[1], Deivid Willian da Fonseca Batistão[2] and Rosineide Marques Ribas[2]
[1]. Faculdade de Medicina, Universidade Federal de Uberlândia, Uberlândia, MG. [2]. Programa de Pós-Graduação em Imunologia e Parasitologia Aplicadas,
Universidade de Uberlândia, Uberlândia, MG.ly