WAR AGAINST BACTERIAL RESISTANCE: VICTORY VS TRUCE
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The enormous world of microorganism source antibiotics to mankind in the war against pathogenic microbes. These microbes in turn tilt the balance to their favor by acquiring resistance against antibiotics, through borrowed genes from a pool widely distributed in the microbial world itself. This collateral damage of misuse of antibiotics on one patient is not limited to that patient, but affects whole society, through expansion of environmental resistome. Both antibiotics and resistance are secondary metabolites involved in varied process, with existence history of million years. Therefore, any antibiotic that would be discovered in future, resistance against it would already be existing in microbial world, which will be acquired by the target bacteria sooner or later. The fight against infection cannot not be won with antibiotics, but truce may be attained through infection control and antibiotic stewardship.
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WAR AGAINST BACTERIAL RESISTANCE: VICTORY VS TRUCE
- 1. WAR AGAINST BACTERIAL RESISTANCE VICTORY VS TRUCE Dr. Ubaidur Rahaman MD (Internal Medicine), EDIC Internist and Critical Care Specialist
- 2. Here is a hypothetical illustration. Mr X has a sore throat. He buys some penicillin and gives himself, not enough to kill the streptococci but enough to educate them to resist penicillin. He then infects his wife. Mrs X gets pneumonia and is treated with penicillin. As the streptococci are now resistant to penicillin the treatment fails. Mrs. X dies. Who is primarily responsible for Mrs. Xās death?ā āThe time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily under dose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant.
- 3. 1940 Penicillinase E. coli Penicillin 1943 Streptomycin 1944 1947 Penicillinase R Staph 1945 Streptomycin R Chloramphenicol and Polymyxin 1947 Erythromycin 1953 Bacitracin 1945 Tetracycline 1950 RESISTANCE AND ANTIBIOTIC DISCOVERY WALKED TOGETHER Methicillin 1960 Ampicillin
- 4. 10,000 ACTINOMYCETES SCREENED 2500 PRODUCE ANTIBIOTIC 2250 STREPTOTHRICIN 125 STREPTOMYCIN 40 TETRACYCLINE 1/100,000 VANCOMYCIN 1/1000,000 ERYTHROMYCIN 1/10,000,000 DATPOMYCIN Jon Clardy, Michael Fischbach, and Cameron Currie. The natural history of antibiotics. Curr Biol. 2009 June 9; 19(11): R437āR441. Nearly all the antibiotics discoveries, with few exception (trimethoprim, monobactams, fosfomycin and cabapenems), were serendipitous by empirical screening not innovative.
- 5. Erythromycin 1953 Tetracycline 1950 RESISTANCE IS A EMERGING PROBLEM 1959 Tetracycline R Shigella Methicillin 1960 Gentamycin 1967 Vancomycin 1972 Imipenem and Ceftazidime 1985 Levofloxacin 1996 Linezolid 2000 Ceftaroline 2010 1962 Methicillin R Staph 1968 Erythromycin R Streptococcus 1979 Gentamycin R Enterococcus 1987 Ceftazidime R Enterobacteriaceae 1988 Vancomycin R Enterococcus 1996 Levofloxacin R Pneumococcus 1998 Imipenem R Enterobacteria 2001 Linezolid R Staphylococcus 2002 Vancomycin R Staphylococcus 2004/5 PDR Acinetobacter and Pseudomonas 2009 PDR Enterobacteriaceae 2011 Ceftaroline R Staphylococcus
- 6. DISCOVERY VOID OF ANTIBIOTICS (dates are reported initial discovery or patent) 1920 1930 1940 1950 1960 1970 1980 1990 2000 2010 PENICILLIN SULFONAMIDE SREPTOMYCIN BACITRACIN NITROFURAN CHLORAMPHENICOL POLYMYXIN CHLOROTETRACYCLIN CEPHALOSPRORIN ERYTHROMYCIN ISONIAZID VANCOMYCIN CYCLOSERINE NOVOBIOCIN RIFAMPICIN METRONIDAZOLE LINCOMYCIN TRIMETHOPRIM NALIDIXIC ACID FUSIDIC ACID MUPIROCIN CARBAPENEM MONOBACTUM OXAZOLIDINONE FOSFOMYCIN DAPTOMYCIN DISCOVERY VOID Lynn L. Silver. Challenges of Antibacterial Discovery. CLINICAL MICROBIOLOGY REVIEWS, Jan. 2011, p. 71ā109
- 7. 1940 1950 1960 1970 1980 1990 2000 PENICILLINASE DISCOVERY ANTIBIOTIC RESISTANCE PLASMID TRANSMISSIBLE FLOUROQUINOLONE RESISTNCE INCREASING ANTIBIOTIC RESISTANCE THE DARK AGE (SEMMELWEIS) DISENCHANTMENT (SEMMELWEIS) (AGAIN) PHARMACOLOGIC BIOCHEMICAL TARGET GENOMIC HTSPRIMORDIAL GOLDEN FDA OFFICE OF NEW DRUG Julian Davies* and Dorothy Davies . Origins and Evolution of Antibiotic Resistance. MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, Sept. 2010, p. 417ā433 COMPLETING A FULL CIRCLE
- 8. ā¢ Enterococcus faecium (VRE)E ā¢ Staphylococcus aureus (MRSA)S ā¢ Clostridium difficileC ā¢ Acinatobaer baumanniiA ā¢ PseudomonasP ā¢ Enterobacteriaceae (CRE)E
- 9. WHO REALLY DISCOVERED ANTIBIOTICS? WHO IS THE FIRST FARMER?
- 10. DESPITE UTILIZING ANTIBIOTICS OVER MILLIONS OF YEARS, ANTIBIOTIC RESISTANCE DID NOT DEVELOP IN WILD ENVIRONMENT OF ATTINI ANTS[9], WHILE HUMANS COULD NOT PREVENT THIS CATASTROPHE IN JUST 80 YEARS OF USE
- 12. RESISTANCE IS ANCIENT Soldier died in WW1 (March 1915) Shigella flexneri R to Penicillin and Erythromycin Penicillin discovered in 1929 Erythromycin discovered in 1953 Soil from beringian permafrost, place near bering strait in Alaska genes encoding resistance to beta lactam, tetracycline and glycopeptide antibiotics ESBL enzymes originated more than two billion years ago Beta lactamase is evolving for more than 100 million years
- 13. Abraham, E. P., and E. Chain. 1940. An enzyme from bacteria able to destroy penicillin. Rev. Infect. Dis. 10:677ā678. ANTIBIOTICS AND RESISTANCE ARE PRESENT IN MICROBIAL WORLD FOR MILLENNIA, WE ONLY ACKNOWLEDGED ITS EXISTENCE RECENTLY. ANTIBIOTICS AND RESISTANCE ARE ANCIENT
- 14. WHAT IS THE ROLE OF SO CALLED ANTIBIOTICS AND RESISTANCE IN NATURE? ANTIBIOTICS QUORUM SENSING BIOFILM FORMATION VIRULENCE IMMUNO- MODULATION ANTIBIOTICS ARE MESSENGER RESISTANCE ARE BLOCKERS Grace Yim, Helena Huimi Wang, Julian Davies. The truth about antibiotics. International Journal of Medical Microbiology 296 (2006) 163ā170
- 15. WHAT IS THE ROLE OF SO CALLED ANTIBIOTICS AND RESISTANCE IN NATURE? Diego Romero, Matthew F. Traxler, Daniel LĆ³pez, Roberto Kolter. Antibiotics as Signal Molecules. Chem Rev. 2011 Sep 14; 111(9): 5492ā5505. ā¢ ABILITY TO INDUCE DIVERSE RESPONSE DEPENDING ON CONCENTRATION USED HORMESIS SO CALLED ANTIBIOTICS ARE NOT MEANT FOR ANTIBIOSIS IN NATURE, IT EXERTS THIS EFFECT ONLY IN CONCENTRATION MUCH ABOVE THAN PRESENT IN NATURE
- 17. 1962 SIR FRANK MACFARLANE BURNET Virologist and immunologist āone can think of the middle of the 20th century as the end of one of the most important social revolutions in history, the virtual elimination of the infectious diseases as a significant factor in social lifeā Gerald B. Pier. On the Greatly Exaggerated Reports of the Death of Infectious Diseases. Clin Infect Dis 2008;47(8):1113-4 Rustam I. Aminov. The role of antibiotics and antibiotic resistance in nature. Environ Microbiol 2009;11(12), 2970-88. BUTā¦.. COMPLACENCY PREVAILED 1965 Dr WILLIAM J. STEWART US SURGEON GENERAL āIt is time to close the book on infectious diseases, and declare the war against pestilence wonā
- 18. 1968 USPUBLICHEALTHSERVICE āThe emphasis of epidemiologic investigation has shifted markedly in the last two decades. A decline in the interest in the infectious diseases and increase in concern with the non-infectious diseases has resulted from the change in relative importance of these categories of disease in many parts of the world, including the United States. It is also recognized that, although major tasks still remain in the improvement of control over the infectious diseases [emphasis added]. . .the identification of cigarette smoking as the major cause of this centuryās epidemic of lung cancer. . .[and] chronic diseases. . .now constitute the predominant health problems in this country.ā BUTā¦.. COMPLACENCY PREVAILED It was presumed initially, that antibiotic resistance would largely be result of target modification through MUTATION which will remain limited to bacterial clone by VERTICAL INHERITANCE.
- 19. Cell-to-cell contact was required for resistance-gene transfer, indicating that bacterial conjugation was involved. This was subsequently confirmed by experiments that showed that blending (agitation) interfered with transfer. Multiple antibiotic resistance of Shigella dysenteriae strains could be transferred to other Enterobacteriaceae, simply by mixing liquid cultures of resistant and sensitive bacteria and plating on solid medium containing the appropriate antibiotics as selective agents WAR TORN JAPAN 1959 Epidemic multidrug resistant Shigella dysenteriae (Streptomycin, Chloramphenicol, Tetracycline, Sulfonamide) HGT
- 20. Naomi Dutta UNITED KINGDOM 1959 multidrug resistant Salmonella typhimurium G. LEBEK obtained evidence for transferable, multiple antibiotic resistance in Salmonella typhimurium and E. coli isolated from children in 1960. The presentation of his results was met with āharsh and unpleasantā criticism (his words) in Munich and LEBEK was dismissed. He was unemployed for several months and then accepted a position in Bern, Switzerland. A report of his work was eventually published in 1963 Lebek G. Uber die Enstehung mehrfachresistanter Salmonellen- Ein experimenteller Beitrag. Zbl. Bact., Dept. I, Orig. 1963;188:494-499. HGT
- 21. BORROWER BACTERIA RESISTANCE GENE DONOR BACTERIA CARBAPENEM R ENTEROBAC, ACINATOBACTER, PSEUDOMONAS blaCTX-M KLUYVERA CARBAPENEM R ENTEROBAC, ACINATOBACTER, PSEUDOMONAS blaNDM ERYTHROBACTER LITORALIS VRSA VanA VRE
- 22. HGT Plasmid carry considerable variety of genes determining resistance to multiple antibiotics as well as genes conferring virulence to bacterium.
- 23. MILLION YEARS OF MACRO EVOLUTION BY MAINLY VERTICAL GENE TRANSFER (MUTATION) 80 YEARS OF MICRO EVOLUTION MAINLY BY HGT EVOLUTION OF ANTIBIOTIC RESISTANCE AND SELECTION PRESSURE
- 24. PAN MICROBIOME, PANGENOME AND RESISTOME PAN MICROBIOME A B C D E F G H I J PANGENO ME RESISTO ME PANGENOME
- 25. GLOBAL MICROBIOME PANGENOME PANPROTEOME MOBILOZOME RESISTOME PARVOME CLINICALLY IMPORTANT RESISTANCE GENES CLINICALLY IMPORTANT ANTIBIOTIC MOLECULES HUMAN ANTIBIOTIC PRODUCTION Gillings MR. Evolutionary consequences of antibiotic use for the resistome, mobilome and microbial pangenome. Front Microbiol. 2013 Jan 22;4:4. CONCEPTUAL REPRESENTATION OF THE BIOLOGICAL MOLECULES OF RELEVANCE TO ANTIBIOTIC RESISTANCE.
- 26. CLINICAL ECOSYSTEM HIGH SELECTION PRESSURE NON-CLINICAL ECOSYSTEM MODERATE SELECTION PRESSURE ENVIRONMENTAL ECOSYSTEM RESISTOME Eileen R. Choffnes, David A. Relman, Alison Mack. Antibiotic resistance: implications for global health and novel intervention strategies: workshop summary rapporteurs; Forum on Microbial Threats, Board on Global Health, Institute of Medicine of the National Academies. United States: Washington D.C. National Academies Press; 2010. EXPANSION OF RESISTOME
- 27. Animals- Prophylaxis and Growth Promotor 70% Animals- Therapeutic 6% Humans- Therapeutics 9% Others- Pesticides etc 15% ANTIBIOTIC EXPLOITATION
- 28. WATER TREATMENT PLANT/ SEWER RIVER/ SOIL EXPANSION OF ENVIRONMENT RESISTOME ANTIBIOTIC RESISTANCE AND WASTE DISPOSAL
- 30. CLINICAL ECOSYSTEM HIGH SELECTION PRESSURE NON-CLINICAL ECOSYSTEM MODERATE SELECTION PRESSURE ENVIRONMENTAL ECOSYSTEM RESISTOME Eileen R. Choffnes, David A. Relman, Alison Mack. Antibiotic resistance: implications for global health and novel intervention strategies: workshop summary rapporteurs; Forum on Microbial Threats, Board on Global Health, Institute of Medicine of the National Academies. United States: Washington D.C. National Academies Press; 2010. EXPANSION OF RESISTOME
- 31. BREACH IC HAI INJUDICIOUS ANTIBIOTICS AMR RESISTANT MICROBIOTIA OF SKIN AND GIT RESISTANT MICROBIOTA OF ENVIRONMENT/ SURFACE BREACHED IC SPREAD TO OTHER PATIENTS PATIENT DISCHARGED SPREADS RESISTANT MICROBIOTA- CONTACT / FEACES EXPANSION OF COMMUNITY RESISTOME PATIENT ADMITTED TO HOSPITAL
- 32. Help us from antibiotic pollution These humans polluted our environment with our secondary metabolites Not to worry mates. Borrow these variety of resistance genes How come man forget, We produce antibiotics as well as resistance. they are unleashing havoc on our siblings with weapon provided by us. We will enrich our colleagues with counter weapons They call it antibiotics Our genes will prevail over humans wits AMP C MBL MRSA MBL AMP C BACTERIAL SOCIAL SECURITY SYSTEM
- 33. āLong term harm to self, others and environment, when unrestrained individual behavior to maximize personal short-term gain, results in depletion or devastation of resourcesā
- 34. ANTIBIOTICS ARE SOCIETAL DRUGS The collateral damage of misuse of antibiotics on one patient is not limited to that patient, but affects whole society, through expansion of environmental resistome.
- 35. FROM FRIEND TO FOE Pseudomonas Acinatobacter Legionella Strenotrophomonas EVOLUTION OF NEW PATHOGENS HOW BENIGN COMMENSALS/ ENVIRONMENTAL BACTERIA TURN INTO DREADED PATHOGENS Bacteria can evolve rapidly to adapt to environmental change. When the "environment" is the immune response of an infected host, this evolution can turn harmless bacteria into life-threatening pathogens Miskinyte M, Sousa A, Ramiro RS, de Sousa JAM, Kotlinowski J, Caramalho I, MagalhĆ£es S, Soares MP and Gordo I. The Genetic Basis of Escherichia coli Pathoadaptation to Macrophages. PLoS Pathog, 9(12): e1003802
- 36. VIRULENCE VS RESISTANCE RESISTANCE COMES AT EVOLUTIONARY COST OF VIRULENCE RESISTANCE GENE VIRULENC GENE COMBIPACK Beceiro A, TomƔs M, Bou G. Antimicrobial resistance and virulence: a successful or deleterious association in the bacterial world?. Clin Microbiol Rev. 2013;26(2):185-230. HGT
- 37. WHO WILL WIN THE WAR? OUR WITS VERSUS THEIR GENES āFUTURE OF HUMANITY AND MICROBES LIKELY WILL UNFOLD AS EPISODES OF A SUSPENSE THRILLER THAT COULD BE TITLED āOUR WITS VERSUS THEIR GENESāā āAs the climax is arriving, it is becoming more evident that our wits of discovering secondary metabolites of bacteria, and tinkering, producing and using it as antibiotic in exuberant amount, cannot not keep pace with bacterial ability to manipulate its genetic pool of resistanceā
- 38. WE CAN NEVER WIN THE WAR WITH ANTIBIOTICS ALONE
- 40. SOLUTION- VICTORY VERSUS TRUCE ANY ANTIBIOTIC THAT WOULD BE DISCOVERED IN FUTURE, RESISTANCE AGAINST IT WOULD ALREADY BE EXISTING IN MICROBIAL WORLD, WHICH WILL BE ACQUIRED BY THE TARGET BACTERIA SOONER OR LATER. EXPANSION OF ENVIRONMETAL RESISTOME ANTIBIOTIC SELECTION PRESSURE
- 41. SOLUTION- VICTORY VERSUS TRUCE ā¢ STOP ANTIBIOTIC USE ā¢ ELIMINATE SELECTION PRESSURE VICTORY IMPOSSIBLE ā¢ PREVENT INFECTION AND JUDICIOUS ANTIBIOTIC USE ā¢ REDUCE SELECTION PRESSURE TRUCE POSSIBLE ā¢ PREVENT INFECTION ā INFECTION CONTROL ā¢ JUDICIOUS USE OF ANTIBIOTIC- ANTIBIOTIC STEWARDSHIP PROGRAM ā¢ DICOURAGE ANTIBIOTIC USE IN ANIMALS AND AGRICULTURE TRUCE
- 42. MILLION YEARS OF MACRO EVOLUTION BY MAINLY VERTICAL GENE TRANSFER (MUTATION) 80 YEARS OF MICRO EVOLUTION MAINLY BY HGT TRUCE MINIMIZE EVOLUTIONARY PRESSURE MINIMIZE EXPANSION OF RESISTOME
- 43. INFECTION CONTROL STANDARD PRECAUTION TRANSMISSION BASED PRECAUTION ā¢ (STANDARD, DROPLET AND AIRBORNE) HAND HYGEINE PPE ENVIRONMENTAL CLEANING COUGH ETIQUETTES ANTIBIOTIC STEWARDSHIP RIGHT DRUG RIGHT DOSE DE-ESCALATION RIGHT DURATION PHARMACOKINETIC/ DYNAMICS HOSPITAL ANTIBIOGRAM ANTIBIOTIC SENSITIVITY TESTING GOVERNMENT REGULATING AGENCY PHARMACEUTICAL INDUSTRY must be reflected in clinical examination, nursing care and invasive procedure Maximize clinical outcome and minimize collateral damage
- 44. Yong, Ed. I Contain Multitudes: The Microbes Within Us and a Grander View of Life (Kindle Location 1). Random House. Kindle Edition.
Editor's Notes
- For a short period of time, drug company chemists managed to keep ahead in the race against antibiotic resistance by making slight changes in the structures of their antibiotics. The synthesis of semi-synthetic methicillin, which was Ī²-lactamase stable, temporarily rescued the failure of the penicillin (142). Meanwhile, the production of ampicillin, another semi-synthetic Ī²- lactam antibiotic, inhibited a wide range of Gram-negative organisms, including Escherichia coli, Haemophilus influenzae, Salmonella Typhi and Shigella. As a result of the explosive antibiotic development, the market was crowded with more than one hundred antibacterial agents (143). Thinking that they had won a total victory, many pharmaceutical firms started to withdraw the efforts to develop new antibiotics in the 1980s, instead focusing on drugs for chronic illnesses such as heart disease, cancer and diabetes, the leading causes of mortality and morbidity in developed countries (128). Thus far, antibiotics have been used with unrestrained passion far surpassing the needs of management and infection control.
- Some antibiotic gene clusters are cosmopolitan, while others have cameo roles. One analysis estimated that if 10,000 actinomycetes (the family of soil bacteria that has produced most of our antibiotics and other medically useful molecules) were screened, 2,500 would produce antibiotics. Of these, 2,250 would make streptothricin, 125 streptomycin, and 40 tetracycline. Vancomycin is predicted to be made by one in a hundred thousand; erythromycin, by one in a million; and daptomycin, our newest antibiotic, by one in ten million. Because the soil bacteria that produced so many of our antibiotics live in exceptionally complex multispecies environments, tracing both neighbors and ancestors will be a daunting task.
- History of antibiotic discovery and concomitant development of antibiotic resistance. The dark ages, the preantibiotic era; primordial, the advent of chemotherapy, via the sulfonamides; golden, the halcyon years when most of the antibiotics used today were discovered; the lean years, the low point of new antibiotic discovery and development; pharmacologic, attempts were made to understand and improve the use of antibiotics by dosing, administration, etc.; biochemical, knowledge of the biochemical actions of antibiotics and resistance mechanisms led to chemical modification studies to avoid resistance; target, mode-of-action and genetic studies led to efforts to design new compounds; genomic/HTS, genome sequencing methodology was used to predict essential targets for incorporation into high-throughput screening assays; disenchantment, with the failure of the enormous investment in genome-based methods, many companies discontinued their discovery programs. Other milestones in this history include the creation of the FDA Office of New Drugs after the thalidomide disaster led to stricter requirements for drug safety, including the use of antibiotics. This slowed the registration of novel compounds. Before antibiotics were discovered, Semmelweis advocated hand washing as a way of avoiding infection; this practice is now strongly recommended as a method to prevent transmission.
- ATTINI ANTS, SCOVOSPIS A FUNGUS PARASITE, ACTINOMYCES BACTERIA Roughly 50 million years ago in South America, a lone species of ant abandoned its primitive hunterāgatherer ways and, in a unique event in ant evolution, adopted an agrarian lifestyle. Entering into a partnership with a parasol mushroom, these agricultural pioneers learned to weed, manure and propagate their fungal crops, ensuring a reliable source of food. From this innovative ancestral stock arose the ant group Attini, of which there are now about 210 species, largely concentrated in wet, South American forests. The Attini include the well-known leaf cutting ants, in which the association (or āsymbiosisā) between ants and fungi has become enormously successful. Colonies of some Atta species may contain eight million ants, with the collective biomass of an adult cow. These ants cut a cowās daily requirement of fresh vegetation, but they do not directly consume it. Instead, by chewing it into a pulp, they convert the vegetation into a substrate on which their fungal crops are grown. The fungus, in turn, produces specialized structures known as gongylidia, which serve as food for the ants. This arrangement has been called an āunholy allianceā1, because it combines the antsā ability to circumvent plant antifungal defences (such as the waxy coatings of leaves, which the ants scrape away) with the ability of the fungus to subvert plant anti-insect defences (such as chemical insecticides, which are digested by the fungus, so are absent from the fungal tissue consumed by the ants). Ā scovopsis is held in check by specific antibiotics produced by bacteria living on the bodies of the ants. It seems hardly a coincidence that these bacteria belong to the genus Streptomyces, from which over half of the antibiotics used by humans are derived. Like the parallels between ant and human agriculture 9 , understanding this use of antibiotics by ants could be directly relevant to human survival. For example, whereas humans have been using antibiotics for fewer than 60 years (longer if you consider the medicinal use of moulds in the ancient Far East, or among the Greeks and Romans), ants have been using them for 50 million years.
- Soil bacteria possesses the ability to make antibiotics, as well as to live with antibiotics. Bacteria have been exposed to antibiotics produced by other competing microorganisms for millennia. Antibiotic resistance genes have a long evolutionary history predating well before the discovery and exposure of antibiotics in concentration much above that produced in nature and resultant selection pressure. Many biosynthetic gene clusters that make āantibioticsā are also known contain genes that confer āresistanceā to those same antibiotics.
- The common resource of antibiotics is not meant for antibiosis in nature, rather they exert this effect when applied at unnaturally high concentrations and bacteria combat this environmental pollution with expression of resistance. Injudicious use of antibiotics in humans, agriculture and animal husbandry has resulted in selection and spread of resistance in clinical, commensal as well as environmental bacteria
- in 1959-60, it was found that the multiple antibiotic resistance of Shigella dysenteriae strains could be transferred to other Enterobacteriaceae, simply by mixing liquid cultures of resistant and sensitive bacteria and plating on solid medium containing the appropriate antibiotics as selective agents (OCHIAeIt al. 1959; AKIBA et al. 1960). The mechanism by which the transfer occurred was revealed when the laboratories of s. MITSUHASHI (HARADA et al. 1960), R. NAKAY(ANA KAYAa nd NAKAMURA19 60a), and T. WATANABE (WATANABanEd FUKUSAW1A96 0a) all showedt hat cell-to-cell contact was required for resistance-gene transfer, indicating that bacterial conjugation was involved. This was subsequently confirmed by experiments that showed that blending (agitation) interfered with transfer and that acridine orange treatmoefn t m ultiply resistant strains caused loss of the resistance determinants
- But discovery of horizontal transfer (HGT) of resistance genes via plasmid came out to be fundamental challenge to this model. Plasmid carry considerable variety of genes determining resistance to multiple antibiotics as well as genes conferring virulence to bacterium. HGT enables bacteria to share resistant genes between themselves as survival tool.[21] This pool of vertically transmitted genes accrued over million years of evolutionary advantage, can be distributed horizontally in a single generation under antibiotic selection pressure, via HGT.
- This sharing of genes is so ubiquitous that entire bacterial world can be considered a pan organism containing pangenome[22]. Part of pangenome encoding resistance is termed as resistome, a common pool shared between all bacteria, benign or pathogenic, native to soil, animal or human[
- Ā The small cross-hatched boxes represent the antibiotics and resistance genes of relevance to clinical practice. Respectively, these are a small subset of the world of small bioactive molecules (the parvome), and the world of potential resistance determinants (the resistome). The resistome comprises the genes that potentially encode resistance to antibiotics. The mobilome comprises the mobile proportion of bacterial genomes. The mobilome and resistome overlap, since many resistance genes are located on mobile elements. Both the resistome and mobilome are a subset of the total coding capacity of prokaryotic cells, the pangenome, which is expressed as the panproteome. Note that only a small proportion of the parvome is utilized by humans for antibiotic purposes, and that the scale of commercial antibiotic production probably overwhelms the natural production of these molecules by the entire global microbiota.
- Antibiotic prescription review of multiple hospitals in 10 U.S. states expressed need to improve antibiotic prescribing in 37% of cases[29]. Data have revealed that in intensive care units 30% to 60% of prescribed antibiotics have been found to be unnecessary and inappropriate
- In agriculture and animal husbandry use of antibiotics for infection prevention and growth promotion should be strongly discouraged and vaccination and improved hygiene and welfare practices should be promoted. Antibiotics should be given for treating infection under veterinary supervision
- But discovery of horizontal transfer (HGT) of resistance genes via plasmid came out to be fundamental challenge to this model. Plasmid carry considerable variety of genes determining resistance to multiple antibiotics as well as genes conferring virulence to bacterium. HGT enables bacteria to share resistant genes between themselves as survival tool.[21] This pool of vertically transmitted genes accrued over million years of evolutionary advantage, can be distributed horizontally in a single generation under antibiotic selection pressure, via HGT.