Sun .19 Oct 2019
TR | RU | UK | KK | BE |

New Delhi metallo-beta-lactamase 1

new delhi metallo-beta-lactamase 1
New Delhi metallo-beta-lactamase 1 NDM-1 is an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotics These include the antibiotics of the carbapenem family, which are a mainstay for the treatment of antibiotic-resistant bacterial infections The gene for NDM-1 is one member of a large gene family that encodes beta-lactamase enzymes called carbapenemases Bacteria that produce carbapenemases are often referred to in the news media as "superbugs" because infections caused by them are difficult to treat Such bacteria are usually susceptible only to polymyxins and tigecycline

NDM-1 was first detected in a Klebsiella pneumoniae isolate from a Swedish patient of Indian origin in 2008 It was later detected in bacteria in India, Pakistan, the United Kingdom, the United States, Canada, and Japan

The most common bacteria that make this enzyme are gram-negative such as Escherichia coli and Klebsiella pneumoniae, but the gene for NDM-1 can spread from one strain of bacteria to another by horizontal gene transfer


  • 1 Enzyme function
  • 2 Origin and spread
  • 3 Phenotypic detection of NDM-1
  • 4 Criticism of enzyme name
  • 5 The Lancet naming apology and aftermath
  • 6 First death
  • 7 See also
  • 8 References
  • 9 External links

Enzyme function

Structure of the carbapenem backbone

Carbapenems are a class of beta-lactam antibiotics that are capable of killing most bacteria by inhibiting the synthesis of one of their cell wall layers The carbapenems were developed to overcome antibiotic resistance mediated by bacterial beta-lactamase enzymes However, the blaNDM-1 gene produces NDM-1, which is a carbapenemase beta-lactamase - an enzyme that hydrolyzes and inactivates these carbapenem antibiotics

Carbapenemases are particularly dangerous resistance mechanisms, since they can inactivate a wide range of different antibiotics The NDM-1 enzyme is one of the class B metallo-beta-lactamase; other types of carbapenemase are class A or class D beta-lactamases The class A Klebsiella pneumoniae carbapenemase KPC is currently the most common carbapenemase, which was first detected in North Carolina, United States, in 1996 and has since spread worldwide A later publication indicated that Enterobacteriaceae that produce KPC were becoming common in the United States

The resistance conferred by this gene blaNDM-1, therefore, aids the expansion of bacteria that carry it throughout a human host, since they will face less opposition/competition from populations of antibiotic-sensitive bacteria, which will be diminished by the original antibacterial treatment

Two zinc ions present in the active binding site

NDM-1 functions through two zinc ions present in the active site that cause hydrolysis of the beta-lactams, rendering them ineffective

Origin and spread

The NDM-1 enzyme was named after New Delhi, the capital city of India, as it was first described by Yong et al in December 2009 in a Swedish national who fell ill with an antibiotic-resistant bacterial infection that he acquired in India The infection was identified as a carbapenem-resistant Klebsiella pneumoniae strain bearing the novel gene blaNDM-1 The authors concluded that the new resistance mechanism "clearly arose in India, but there are few data arising from India to suggest how widespread it is" Its exact geographical origin, however, has not been conclusively verified In March 2010, a study in a hospital in Mumbai found that most carbapenem-resistant bacteria isolated from patients carried the blaNDM-1 gene Later, the journal authority apologized for using the name of New Delhi, India to describe a pathogen

NDM-1 β-lactamase was also found in an K pneumoniae isolate from Croatia, and the patient arrived from Bosnia and Herzegovina The second geographical origin is considered to be eastern Balkans

In May 2010, a case of infection with E coli expressing NDM-1 was reported in Coventry in the United Kingdom The patient was a man of Indian origin who had visited India 18 months previously, where he had undergone dialysis In initial assays the bacterium was fully resistant to all antibiotics tested, while later tests found that it was susceptible to tigecycline and colistin The authors warned that international travel and patients' use of multiple countries' healthcare systems could lead to the "rapid spread of NDM-1 with potentially serious consequences"

As of June 2010, there were three reported cases of Enterobacteriaceae isolates bearing this newly described resistance mechanism in the US, the Centers for Disease Control and Prevention CDC stated that "All three US isolates were from patients having received recent medical care in India" However, US experts stated that it is unclear as to whether this strain is any more dangerous than existing antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus, which are already common in the USA

Structure of colistin, one of the few antibiotics able to treat NDM-1 positive bacterial infections

In July 2010, a team in New Delhi reported a cluster of three cases of Acinetobacter baumannii bearing blaNDM-1 that were found in the intensive care unit of a hospital in Chennai, India, in April 2010 As previously, the bacteria were fully resistant to all the aminoglycoside β-lactam and quinolone antibiotics, but were susceptible to tigecycline and colistin This particularly broad spectrum of antibiotic resistance was heightened by the strain's expressing several different resistance genes in addition to blaNDM-1

A study by a multi-national team was published in the August 2010 issue of the journal The Lancet Infectious Diseases This examined the emergence and spread of bacteria carrying the blaNDM-1 gene This reported on 37 cases in the United Kingdom, 44 isolates with NDM-1in Chennai, 26 in Haryana, and 73 in various other sites in Pakistan and India The authors' analysis of the strains showed that many carried blaNDM-1 on plasmids, which will allow the gene to be readily transferred between different strains of bacteria by horizontal gene transfer All the isolates were resistant to multiple different classes of antibiotics, including beta-lactam antibiotics, fluoroquinolones, and aminoglycosides, but most were still susceptible to the polymyxin antibiotic colistin

On 21 August 2010, Ontario, Canada, had its first confirmed case of the "superbug" in Brampton There were other confirmed cases in British Columbia and Alberta These confirmed NDM-1 infected cases have no relationship with New Delhi, India The patients or their relatives never travelled India in the last decade

In August 2010, a chemical compound GSK 299423 was found to significantly fight against antibiotic-resistant bacteria by making such bacteria unable to reproduce, citing a likely treatment to the NDM-1 strain

On 6 September 2010, Japan detected its first ever case of the NDM-1 enzyme In May 2009, a Japanese man in his 50s who had recently returned from vacation in India was struck with a fever and hospitalized, later making a full recovery Hospital officials confirmed that tests carried out after the patient's recovery were positive for the NDM-1 enzyme

An environmental point prevalence study conducted between 26 September and 10 October 2010 found bacteria with the NDM-1 gene in drinking water and seepage samples in New Delhi 50 tap water samples and 171 seepage samples were collected from sites within 12 km of central New Delhi Of these samples, 20 strains of bacteria were found to contain NDM-1 gene in 51 out of 171 seepage samples and 2 out of 50 tap water samples

On 8 May 2012, the presence of NDM was found in a patient who died at Royal Alexandra Hospital in Edmonton, Alberta The patient was also found to be carrying an Acinetobacter strain The patient contracted the bacteria after another patient, who had surgery on the Indian subcontinent, traveled to Canada and was admitted to hospital with an infection

Science Daily reported on the 16 December 2013 that a team of scientists from Rice, Nankai and Tianjin universities found NDM-1 in two wastewater treatment plants in northern China In fact, the NDM-1 was unable to be removed after several treatments and attempts to disinfect the plants Disinfection by chlorine, one of the most effective methods currently, also failed to eradicate the beta-lactamase

In June 2014 it was reported that the molecule aspergillomarasmine A from the Aspergillus fungus turns off the resistance mechanism of NDM-1 and thus makes bacteria once again sensitive to traditional antibiotics It has been shown to be effective in mice and rats but has not yet been tested in humans for safety or effectiveness

In September 2016, a 70-year-old woman in Reno, Nevada, died of septic shock following infection with NDM-producing Klebsiella pneumoniae She had been on an extended trip to India and was admitted to a hospital there for an infected right hip

Phenotypic detection of NDM-1

Detection of NDM-1 gene depends upon the phenotypic determination of the enzyme activity These enzymes are zinc dependent and therefore termed as metallo-beta-lactamase Indian studies have been done which demonstrate their dependency on zinc and the ability of zinc chelating agents like EDTA to decrease their activity The Modified Hodge Test and the Re-Modified Hodge Test were developed for detection on a routine basis in resource limited laboratories Other tests for phenotypic detection are:

  • Double disk synergy testing DDST
  • Vitek detection Automated system
  • E-test E-Strip

Criticism of enzyme name

The Indian health ministry has disputed the conclusion of the August 2010 Lancet study that the gene originated in India, describing this conclusion as "unfair" and stating that Indian hospitals are perfectly safe for treatment Indian politicians have described linking this new drug resistance gene to India as "malicious propaganda" and blamed multinational corporations for what they describe as selective malignancy A Bharatiya Janata Party politician has instead argued that the journal article is bogus and represented an attempt to scare medical tourists away from India The Indian Ministry of Health released a statement "strongly refut" naming the enzyme "New Delhi" A co-author of the 2010 Lancet study, who is based in the University of Madras, has stated that he does not agree with the part of the article that advises people to avoid elective surgeries in India

In contrast, an editorial in the March 2010 issue of the Journal of Association of Physicians of India blamed the emergence of this gene on the widespread misuse of antibiotics in the Indian healthcare system, stating that Indian doctors have "not yet taken the issue of antibiotic resistance seriously" and noting little control over the prescription of antibiotics by doctors and even pharmacists The Times of India states that there is general agreement among experts that India needs both an improved policy to control the use of antibiotics and a central registry of antibiotic-resistant infections

The Lancet naming apology and aftermath

The British journal The Lancet refused to publish a rebuttal from the Indian National Centre for Disease Control, claiming lack of space and that the journal's editors felt it would be better placed elsewhere However, on 12 January 2011, the editor of The Lancet, Richard Horton, apologized and acknowledged that naming a superbug after New Delhi was an "error" Following this, Ajai R Singh, editor of Mens Sana Monographs, demanded that such 'geographic names giving' be abandoned and replaced by 'scientific name giving' He proposed changing NDM-1 to PCM plasmid-encoding carbapenem-resistant metallo-beta-lactamase

First death

In August 2010, the first reported death due to bacteria expressing the NDM-1 enzyme was recorded after a Belgian man, who had become infected while being treated in a hospital in Pakistan, died despite being administered colistin A doctor involved in his treatment said:"He was involved in a car accident during a trip to Pakistan He was hospitalised with a major leg injury and then repatriated to Belgium, but he was already infected"

See also

  • Antibiotic resistance
  • List of antibiotic resistant bacteria
  • Medical tourism
  • Methicillin-resistant Staphylococcus aureus
  • MCR-1
  • Nosocomial infection
  • Transduction genetics


  1. ^ a b Kumarasamy KK, Toleman MA, Walsh TR, et al August 2010 "Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK:a molecular, biological, and epidemiological study" Lancet Infect Dis 10 9:597–602 doi:101016/S1473-30991070143-2 PMC 2933358  PMID 20705517 
  2. ^ "Health Protection Report" Health Protection Agency 3 July 2009 
  3. ^ Stephen Smith 13 September 2010 "New drug-resistant 'superbug' arrives in Mass" The Boston Globe Retrieved 18 September 2010 
  4. ^ "Superbug detected in GTA" Toronto Star 22 August 2010 
  5. ^ Shino Yuasa 8 September 2010 "Japan confirms first case of superbug gene" The Boston Globe Associated Press Retrieved 14 February 2016 
  6. ^ Hudson, Corey; Bent, Zachary; Meagher, Robert; Williams, Kelly June 7, 2014 "Resistance Determinants and Mobile Genetic Elements of an NDM-1-Encoding Klebsiella pneumoniae Strain" PLOS ONE 9:e99209 doi:101371/journalpone0099209 PMC 4048246  PMID 24905728 
  7. ^ Queenan AM, Bush K July 2007 "Carbapenemases:the versatile beta-lactamases" Clinical Microbiology Reviews 20 3:440–458 doi:101128/CMR00001-07 PMC 1932750  PMID 17630334 
  8. ^ Miriagou V, Cornaglia G, Edelstein M, et al February 2010 "Acquired carbapenemases in Gram-negative bacterial pathogens:detection and surveillance issues" Clin Microbiol Infect 16 2:112–122 doi:101111/j1469-0691200903116x PMID 20085605 
  9. ^ Nordmann P, Cuzon G, Naas T April 2009 "The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria" Lancet Infect Dis 9 4:228–236 doi:101016/S1473-30990970054-4 PMID 19324295 
  10. ^ Cuzon G, Naas T, Nordmann P February 2010 "KPC carbapenemases:what is at stake in clinical microbiology"Pathol Biol Paris in French 58 1:39–45 doi:101016/jpatbio200907026 PMID 19854586 
  11. ^ a b Yong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K, Walsh TR December 2009 "Characterization of a new metallo-beta-lactamase gene, blaNDM-1, and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India" Antimicrob Agents Chemother 53 12:5046–5054 doi:101128/AAC00774-09 PMC 2786356  PMID 19770275 
  12. ^ Deshpande Payal; Rodrigues Camilla; Shetty Anjali; Kapadia Farhad; Hedge Ashit; Soman Rajeev 2010 "New Delhi Metallo-β lactamase NDM-1 in Enterobacteriaceae:Treatment options with Carbapenems Compromised" J Assoc Physicians India 58:147–150 PMID 20848811 
  13. ^ Kalenić, Smilja 2013 Medicinska mikrobiologijain Croatian Zagreb:Medicinska naklada ISBN 978-953-176-637-1 
  14. ^ Muir A, Weinbren MJ July 2010 "New Delhi metallo-beta-lactamase:a cautionary tale" J Hosp Infect 75 3:239–240 doi:101016/jjhin201002005 PMID 20435372 
  15. ^ "Detection of Enterobacteriaceae Isolates Carrying Metallo-Beta-Lactamase — United States, 2010" MMWR Morb Mortal Wkly Rep 59 24:750 25 June 2010 PMID 20577157 
  16. ^ McNeil Jr, Donald G 11 August 2010 "Antibiotic-Resistant Bacteria Moving From South Asia to US" The New York Times Retrieved 13 August 2010 
  17. ^ Karthikeyan K, Thirunarayan MA, Krishnan P July 2010 "Coexistence of blaOXA-23 with blaNDM-1 and armA in clinical isolates of Acinetobacter baumannii from India" J Antimicrob Chemother 65 10:2253–2254 doi:101093/jac/dkq273 PMID 20650909 
  18. ^ "First NDM-1 superbug case confirmed in Ontario" CTV News Archived from the original on 2010-08-24 
  19. ^ "299423:GSK cites progress with a new-gen antibiotic - FierceBiotech" 
  20. ^ Bax BD; et al 4 August 2010 "Type IIA topoisomerase inhibition by a new class of antibacterial agents" Nature 466 7309:935–940 doi:101038/nature09197 PMID 20686482  primary source
  21. ^ Alazraki, Melly 6 August 2010 "GlaxoSmithKline Finds Compound That Could Help Fight 'Superbugs'" dailyfinancecom Retrieved 13 August 2010 
  22. ^ "NDM1 - Origin, Symptoms and Cure for NDM1" 13 August 2010 
  23. ^ "News" 
  24. ^ Walsh, Timothy R; Janis Weeks; David M Livermore; Mark A Toleman 7 April 2011 "Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health:an environmental point prevalence study" The Lancet Infectious Diseases 11 5:355–362 doi:101016/S1473-30991170059-7 PMID 21478057 Retrieved 7 April 2011 
  25. ^ "Antibiotic-resistant bacteria suspected in Royal Alex death" CBC News May 18, 2012 Retrieved 22 January 2017 
  26. ^ a b Yi Luo, Fenxia Yang, Jacques Mathieu, Daqing Mao, Qing Wang, and PJJ Alvarez December 4, 2013, Proliferation of Multidrug-Resistant New Delhi Metallo-β-lactamase Genes in Municipal Wastewater Treatment Plants in Northern China, Environmental Science & Technology Letters, doi:101021/ez400152e
  27. ^ "'Superbugs' found breeding in sewage plants" Science Daily December 16, 2013 Retrieved 22 January 2017 
  28. ^ "Antibiotic-resistant bacteria disarmed with fungus compound" CBC News June 25, 2014 
  29. ^ Chen, Lei; Todd, Randall; Kiehlbauch, Julia; Walters, Maroya; Kallen, Alexander 1 January 2017 "Notes from the Field:Pan-Resistant New Delhi Metallo-Beta-Lactamase-Producing Klebsiella pneumoniae — Washoe County, Nevada, 2016" MMWR Morbidity and Mortality Weekly Report doi:1015585/mmwrmm6601a7 
  30. ^ a b Rai, S; Manchanda, V; Singh, NP; Kaur, IR Jul–Sep 2011 "Zinc-dependent carbapenemases in clinical isolates of family Enterobacteriaceae" Indian journal of medical microbiology 29 3:275–9 doi:104103/0255-085783912 PMID 21860109 
  31. ^ a b Pandey, Geeta 12 August 2010 "India rejects UK scientists' 'superbug' claim" BBC News Retrieved 13 August 2010 
  32. ^ Telegraphcouk:Indian Government angry over claims its hospitals are fuelling global superbug
  33. ^ "Linking India to superbug unfair and wrong, says India" Hindustan Times 12 August 2010 Archived from the original on 14 August 2010 Retrieved 13 August 2010 
  34. ^ "'Superbug' an MNC conspiracy:BJP leader" 
  35. ^ Sharma, Sanchita 13 August 2010 "'Don't blame superbug on India, it's everywhere'" Hindustan Times Archived from the original on 14 August 2010 Retrieved 13 August 2010 
  36. ^ a b Narayan, Pushpa 13 August 2010 "Indian author says superbug report is fudged" The Times of India Retrieved 13 August 2010 
  37. ^ Abdul Ghafur K March 2010 "An obituary- On the Death of antibiotics!" Journal of Association of Physicians of India 58 
  38. ^ Lancet won't publish India's rebuttal, NEW DELHI, Special Correspondent, April 13, 2011, thehinducom
  39. ^ "Lancet says sorry for 'Delhi bug'" The Times Of India 12 January 2011 Retrieved 2011-01-12 
  40. ^ "Science, names giving and names calling:Change NDM-1 to PCM" Mens Sana Monographs Retrieved 2011-03-11 
  41. ^ "Belgian man dies of South Asian superbug" 

External links

  • BBC News Health - Questions&Answers about NDM-1 superbugs
  • National Resistance Alert 3 addendum in UK PDF
  • ESBL Threat already known to exist2004
  • ESBL Possible treatment approach2006
  • Moellering, Robert C December 2010 "NDM-1 — A Cause for Worldwide Concern" N Engl J Med 363:2377–9 doi:101056/NEJMp1011715 PMID 21158655 
  • PBS Frontline Oct 22, 2013 Hunting the Nightmare Bacteria
  • Molecular and Cellular Biology portal

new delhi metallo-beta-lactamase 1

New Delhi metallo-beta-lactamase 1 Information about

New Delhi metallo-beta-lactamase 1

  • user icon

    New Delhi metallo-beta-lactamase 1 beatiful post thanks!


New Delhi metallo-beta-lactamase 1
New Delhi metallo-beta-lactamase 1
New Delhi metallo-beta-lactamase 1 viewing the topic.
New Delhi metallo-beta-lactamase 1 what, New Delhi metallo-beta-lactamase 1 who, New Delhi metallo-beta-lactamase 1 explanation

There are excerpts from wikipedia on this article and video

Random Posts

IP address blocking

IP address blocking

IP address blocking prevents connection between a server or website and certain IP addresses or rang...
Gisele Bündchen

Gisele Bündchen

Gisele Caroline Bündchen1 Portuguese pronunciation: ʒiˈzɛli kaɾoˈlini ˈbĩtʃẽj, German pronuncia...
Sheldon, West Midlands

Sheldon, West Midlands

Sheldon is an area of east Birmingham, England Historically part of Warwickshire, it is close to the...
Beverly, Chicago

Beverly, Chicago

Beverly is one of the 77 community areas of Chicago, Illinois It is located on the South Side on the...