MCB6937 Exam 3
*KNOW* Rapid Dereplication with Genomics and Transcriptomics
"Natural product discovery from microorganisms (the Waksman platform) collapsed owing to overmining The *large background of known compounds makes discovery impractical* *Rapid identification of targets* by *transcription profiling of extracts* will *solve the problem of the large background*, and *new sources of secondary metabolites will produce discovery platforms*"
*KNOW* CLSI
CLSI = *Clinical and Laboratory Standards Institute* -makes standard format and standard lab practices that labs all over the world use -for standardized methods to get accurate/quality results -used by healthcare workers, drug manufacturers, and governmental agencies Formerly known as *National Committee for Clinical Laboratory Standards* (*NCCLS*) -international organization with over 60 countries -*Test standardization* -*Monitor test quality*
*KNOW* Out of 40M people annually who are prescribed antibiotics for respiratory issues:
-27M get antibiotics unnecessarily -Only 13M people actually need them -The *most important diagnostic tools* is the one that will *tell the difference between a viral and a bacterial infections without making assumptions*
Quiz 8: The purpose of antibiotic surveillance is to (check al that apply):
-Better understand AMR patterns -Provide appropriate response
Quiz 9: There are a number of bacterial vaccines available. What are some of them? (Select all that apply)
-Clostridium tetani -Bordetella pertussis
Quiz 8: What are some ways to enhance drug penetration?
-Drug modification -Inhibition of efflux pumps
*KNOW* What is the goal of diagnostic?
-Is the infection bacterial or viral? -What type of bacteria are causing the infection? -Are the bacteria resistant to a particular drug? -Which drugs are the bacteria susceptible to? *Ultimate Goal* of diagnostics is to *provide patients with the best care* and to *provide epidemiological data on disease and resistance*
Quiz 9: Which of the following are parts of the innate immune system? (Check all that apply)
-Skin -Macrophages
Quiz 9: What's the advantage of potential host-directed antimicrobial drugs? (Check all that apply)
-Stimulate the immune system -Enhance the efficacy of antibiotics -Circumvent antibiotic resistance -Low the risk of developing resistance
Quiz 9: Therapeutic vaccines can potentially ___ bacterial infections; however, the challenge with their development is that bacterial infections progress ___ for vaccines to work.
-Treat -Too fast
*KNOW* GLASS Objectives
-foster national surveillance systems and harmonized global standards -estimate the extent and burden of AMR globally by selected indicators -analyze and report data on AMR on a regular basis -detect emerging resistance and its international spread -inform implementation of targeted prevention and control programs -assess the impact of interventions
*KNOW* General Conclusions on the Surveillance of AMR by WHO
-there are many gaps in information on pathogens of major concern -surveillance is neither coordinated nor harmonized -many common treatment options for bacterial infections are becoming ineffective across parts of the world -ABR has a negative impact on outcomes for affected patients and health-care expenditures -very high levels of resistance have been observed in bacteria that cause common HAI and CAI across all WHO regions -use TB, malaria, and HIV as a model to determine disease burden and interventions
*KNOW* Purpose of Surveillance on AMR according to WHO
-to determine the scope of the problem -formulate effective response to AMR -monitor effectiveness of the response to AMR
*KNOW* CDC Provides 4 Core Actions to Battle Antibiotic Resistance
1) Preventing infections, Preventing the spread of resistance -"Avoiding the infections in the fist place reduces the amount of antibiotics that have to be used, and reduces the likelihood that resistance will develop during therapy" -"There are many ways that drug-resistant infections can be prevented: -immunization -safe food preparation -handwashing -using antibiotics as directed and only when necessary -In addition, preventing infections also prevents the spread of resistant bacteria
Control Measures
Actions that we can take to limit or prevent exposure
*KNOW* Vaccine Components
Active Component = Antigen -weakened microbes -inactivated microbes -parts of microbes -modified microbial toxins
*KNOW* What makes us prone to bacterial attack?
All either directly affect the *Immune System* or our *Microbiota* (2 categories) -Microbiota is involved in the regulation of the Immune system, but not well understood *Age* -young and elders are most vulnerable to infections -time of life when immune system is under development, or declining with age *Underlying Conditions* -Diabetes, genetics, etc. *Viral Infections* -Influenza weakens immune system and allows opportunistic infections *Physical Trauma* -Breaks barrier between 2 environments, allowing migration of bacteria *Medical Procedures* -Surgeries, catheters, implants *Antibiotics* *Drugs* -Antifungal, immunosuppressants *Lifestyle* -Smoking, drinking, sleeping *Hygiene* -Poor vs Extreme *Diet* -Malnutrition
*KNOW* Prodrugs
Delivered in inactive form and get activated once inside of a bacterial cell Increases activity against strains overexpressing activating enzymes Examples: -Prontosil -Isoniazid
*KNOW* Dilution Method: MIC
Determines the minimal concentration of antibiotic required to inhibit/kill bacteria Can be done on either solid or liquid media
*KNOW* Target the Host to Enhance the Immune System
Directly target the host so that the immune system works better by itself to clear pathogens and bacteria -without need for antibiotics
*KNOW* Antimicrobial Property of Honey
Antibacterial activity between different honeys can vary by 100-fold MRSA and VRE were as sensitive to antibacterial activity of honey as MSSA and VSE Out of 130 clinical isolates of MDR bacteria, 6-8% honey exhibited MIC for A. baumannii (including pan-resistant strains) and 12-14% for all other bacterial species tested Constant exposure of bacteria to sublethal concentrations of honey did not result in resistance
*KNOW* Scope of Search: Global
Antibiotics and antimicrobial compounds are made by: -Bacteria -Plants -Animals
*KNOW* Antibiotic Prophylaxis for Medical Conditions
Antibiotics are commonly prescribed by physicians for the prevention of: -Herpes simplex virus -Influenza -Rheumatic fever -Recurrent cellulitis -Meningococcal disease -Pertussis -Recurrent uncomplicated UTI -Spontaneous bacterial peritonitis in cirrhosis patients -Infective endocarditis -Acute necrotizing pancreatitis -Open fractures -Prosthetic join replacement -Bite wounds
*KNOW* Peptide Antibiotics are not the Same as Antimicrobial Peptides
Antimicrobial Peptides = synthesized by ribosomes Peptide Antibiotics = are non-ribosomal -no mRNA template
*KNOW* Sweet Wormwood
Artemisinin = most effective treatment against malaria -Extracted from Sweet Wormwood -Youyou Tu received the Nobel Prize in Medicine (2015) for her discovery of artemisinin
*KNOW* The American Dental Association Recommends
As part of the evidence-based approach to care, this clinical recommendation should be integrated with the *practitioner's professional judgments (up to the dentist)* in *consultation with the patient's physician*, and the *patient's needs and preferences (ultimate decision left to the patient)* These considerations include: -Previous artificial join infections and complications -Patients undergoing treatment of oral infections -Increased susceptibility for systemic infections -Immunodeficiencies and immunosuppressive medication -Diabetes -Autoimmune disease (rheumatoid arthritis or lupus) -Extensive and invasive procedures
Quiz 9: A person who carriers an infective organism, but who does not manifest any signs of infection.
Asymptomatic carrier
*KNOW* Virulence Factors
Bacteria are less likely to develop resistance to drugs that target virulence as opposed to drugs that target fitness Inhibition of virulence factors in combination with antibiotics can battles infection of allow clearance by the immune system
Targeting the host to inhibit bacterial infections is a promising approach that can be used instead of antibiotics
This approach can also be used in combination with current antibiotics or molecules that target bacteria -Additive or Synergistic Effect
Quiz 9: You are a scientist working in the Microbiology & Cell Science Department at UF. You've read that Native Indians living in Florida used to treat skin infections by rubbing leaves from the Gatortree. Being very interested in natural anti-infective compounds, you found the Gatortree, collected its leaves, and extracted the fraction that has an antimicrobial effect. After a couple of tests, you found that it's potency in killing MRSA is similar to vancomycin. What can you tell about the active compound?
This is most likely a novel antibacterial compound -it does NOT have a MoA similar to vancomycin, because MoA for plant antimicrobials are not well understood
*KNOW* Current Guidelines on Prophylactic Use of Antibiotics for Prevention of IE
UK: Insufficient evidence on the benefits of prophylactic antibiotic -No antibiotic prophylaxis recommendation remains in effect for dental treatment for patients at high risk for IE The rest of Europe and US continue recommending antibiotic prophylaxis for patients who are at high risk of developing IE
*KNOW* Targeting Host Metabolism Inhibits Bacterial Infection
Under normal conditions, Macs metabolize glucose through glycolysis -End product is pyruvate that enters TCA cycle in mitochondria -Amino acids are also metabolized in mitochondria Czyz found some intracellular bacteria shift the metabolism in the host ell into aerobic glycolysis -means glucose can now ferment into lactic acid in presence of oxygen -Phenomenon is hallmark of cancer cells, known as "the Warburg effect" -means the bacteria most likely feeds on elevated levels of lactic acid inside of the cells
Prophylaxis
Use of antibiotics to prevent any future infections
*KNOW* Diffusion Method: Kirby-Bauer
Uses antibiotic-containing disks to test A paper disk with a standardized quantity of antibiotic generates a concentration gradient of antibiotics in the agar -Zone of Inhibition around the antibiotic disk will form -similar to what was observed by Fleming -Zone of Inhibition is proportional to bacteria's susceptibility to specific antibiotic -Resistant, Intermediate, and Susceptible Procedure and measurements have been standardized by CLSI
*KNOW* Diffusion Method: Stokes Method
Variation of the Kirby-Bauer Method Uses bacteria with *known* antibiotic susceptibility (sensitive) as *control* -unknown bacteria are compared to known Plate is divided into 3 regions: -2 outside regions are seeded with control bacteria with known antibiotic activity -Middle region is seeded with test bacteria
*KNOW* Take-home Messages about GLASS
WHO initiated Global Antimicrobial Resistance Surveillance System (GLASS) -early implementation stage 2016-2019 -majority of countries are still not registered, and many do not report -funding and resources are major limitation Antibiotic resistance surveillance is difficult even at the national level
*KNOW* Targeting Human Cell to Modulate Bacterial Uptake
We can target human cells and still be able to inhibit bacterial infections -but do any of these drugs actually affect bacterial uptake? -Drug inhibits bacterial entry, will only be effective when used *prior* to infection
*KNOW* Immunosuppressing Medical Conditions
i.e. Severe burns, Cancer, HIV/AIDS, Diabetes, Cystic Fibrosis, Organ Transplant Certain medical conditions suppress the ability of the immune system to work properly Immune system can be restored and enhanced with antibiotics -To defend against bacteria -But they do *NOT* stimulate the immune system, and are only good as long as the bacteria are sensitive
*KNPW* Using ancient medicine is not such a bad idea
Hippocrates recommended to drink tea brewed from a Willow Tree bark as a potent fever reducer -later found to be ingredient used in Aspirin
*KNOW* Current and Future Applications of Metal Surfaces
Hospitals are major incubator of superbugs that can survive on surfaces for a long time Coating highly touched areas with copper can prevent the spread of such bugs
*KNOW* Rules of Penetration
Identification of antibiotics against Gram- bacteria is challenging due to intrinsic barrier is not penetrable for most molecules Measuring penetration of a large set of compounds and ranking them will enable the deduction of rules of penetration
*KNOW* Stimulation of the Immune System
If we could find a way to *boost the immune system* to the point that *bacteria would be eliminated before they get a chance to progress into infection*, we can perhaps *decrease the use of antibiotics* or *slow down the development of ABR* Boosting the immune system is not an easy approach -Overactivity can lead to autoimmune diseases
*KNOW* The Immune System
Immune System is orchestrated by complex interactions between organs, tissues, and different bod parts *Innate Immunity* =immediate response that allows the body to respond quickly as the invader is detected -composed of cells that can rapidly mount a response against pathogen with antimicrobial responses -Epithelial barriers -Phagocytes -Dendritic cells -Complement -NK Cells *Adaptive Immunity* =long-term protection against reinfections -response takes much longer than innate -ability to activate the immune response can allow us to fight infections (vaccines are an example of how adaptive is established by using Ag) -B lymphocytes -> Plasma cells -> Ab -APCs -> T lymphocytes -> Effector T cells
*KNOW* Soil Bacteria
In Jordan, people used to rub red soil to treat infected skin and diaper rashes Red soil has antibiotic producing bacteria that have strong antimicrobial activity against S aureus and Micrococcus luteus
*KNOW* Exercise enhances the immune system: Evidence from animal studies
In study of mice that exercised and were sedentary: -Both groups were infected with Salmonella -Exercise group had lower bacterial load across al organs and fecal load -Sedentary group had much more
*KNOW* Innate Immunity
Innate Immunity is composed of specific cells that allow *rapid detection and response* to an invading pathogen -Rapid = minutes to hours Phagocytes: -DCs -Neutrophils -Macs -involved in *direct clearance* of pathogens
*KNOW* Prevention and Control
Only use antibiotics when prescribed by a certified health professional Never demand antibiotics if your health worker says you don't need them Always follow your health worker's advice when using antibiotics Never share or use leftover antibiotics Prevent infections by regularly washing hands, avoiding close contact with sick people, practicing safe sec, and keeping vaccinations up to date Avoid injuries and hospitals Prepare food hygienically, following the WHO 5 Keys to Safer Food -Keep clean, separate raw and cooked, cook thoroughly, keep food at safe temperatures and use safe water -Choose foods that have been produced without the use of antibiotics for growth promotion or disease prevention in healthy animals
*KNOW* Rapid Diagnostics (Point of Care/ POC)
POC Diagnostics -performed at/near patient -*Portable* Rapid turnaround time Provides actionable info that contributes to patients well being
*KNOW* Antibiotic Prophylaxis for Dental Procedures
Patients with underlying heart conditions or those who have prosthetic joints may require antibiotic prior to dental procedures Dental procedures can induce infective endocarditis
*KNOW* Beta-lactamase Testing: Modified Hodge Test (MHT)
Phenotypic test for detection of B-lactamases/carbapenemases The plat contains a carbapenem antibiotic Plate contains 4 strains: 1) *Positive Control* =producer of B-lactamases -K. pneumoniae ATCC BAA-1705 -Carbapenemase producer inhibits carbapenem antibiotic that diffuses from the disk which allows the indicator strain to grow 2) *Negative Control* =no B-lactamase activity -K. pneumoniae ATCC BAA-1706 3) *Test Strain* -shows carbapenemase activity -allows growth of Indicator Strain 4) *Indicator Strain* =sensitive to carbapenems -E. coli ATCC 25922
*KNOW* Rational Design
Prediction of target-binding molecules (molecular docking) Enhancing drug penetration will stimulate rational drug design research -Drug modification -Inhibition of efflux pumps
*KNOW* The American Heart Association Recommends
Prophylaxis against infective endocarditis (IE) as a reasonable practice before dental procedures in patients with the following: -Any prosthetics implanted in the heart -Previous IE -Congenital heart disease -Cardiac transplants and abnormal valves
*KNOW* Challenges Associated with Vaccines
Not 100% effective -selection for resistance Genetic variations between bacteria of the same species hinders vaccine specificity Associated with S. aureus -Numerous virulence mechanisms -All studies targeted cell surface components -Using wrong animal infection models -mice are less sensitive to superantigens compared to humans -i.e. LPS LD in humans ~0.01 ug/kg, in mice >80,000 ug/kg -*rabbits are a better model because they are hypersensitive like humans*
*KNOW* Scope of Search: Phage Therapy
One person's waste is another person's treasure Bacteriophages are not antibiotics -they do provide a good alternative by attacking the bacteria
*KNOW* Does Antibiotic Prophylaxis Really Work?
"Regular toothbrushing and flossing pose a greater risk in relation to both infective endocarditis and prosthetic join infection than episodical dental treatment" "Toothbrushing, flossing, pulsating water irrigators, and interdental woodsticks can all produce bacteremia" -but we don't take antibiotics prior to brushing teeth US: 3 Studied -2 showed no change in IE -1 showed increases in IE, but had design flaws France: No increase in IE -But studies had flaws UK: No change in IE -78.5% reduction in antibiotic prescription -Antibiotic use remained at 2,000 dental prescriptions per month -Another follow-up study 5 years after the "no antibiotic recommendation" showed a significant increase in the incidence of IE -However, during this study the antibiotic prescription still remained at 1,300/month
*KNOW* Waksman Revival: Culturing the Unculturable
"Uncultured microorganisms make up 99% of the total diversity Methods of in situ cultivation followed by domestication will enable drug discovery from this previously inaccessible source Combined with rapid dereplication, this is likely to lead to the revival of the Waksman platform"
*KNOW* What kind of data is collected by GLASS
*8 Priority Pathogens* -E. coli -K. pneumoniae -Acinetobacter spp. -S. aureus -S. pneumoniae -Salmonella spp. -Shigella spp. -Neisseria gonorrhoeae *4 Specimen Types* -Blood -Urine -Stool -Genital Swabs
*KNOW* Handwashing is Important but Difficult to Implement
*Antoine-Germain Labarraque* -developed sodium hypochlorite solution and showed its antiseptic properties by neutralizing the odor from decomposing human corpses Saw benefit in using the solution on physician's hands when treating patients 80% of infectious diseases are transferred by touch -Despite this number, only 40% of healthcare personnel adhere to hand hygiene
*KNOW* Antibiotic Sensitivity Tests
*Diffusion Method* -Kirby-Bauer method (disk diffusion test) -Stokes Method *Dilution Method* -Minimum Inhibitory Concentration (MIC) *Diffusion/Dilution* -E-test
*KNOW* Diagnostic Strategies Fuel AMR
*Empirical Diagnosis* -"educated guess" / no diagnostic tests -nonspecific antibiotic prescription -high potential for failure and development of resistance *Traditional Diagnostics* -takes days (traditional tests with patient specimen) -nonspecific antibiotic prescription: until proper diagnosis is determined -high potential for resistance: because given broad spectrum antibiotic *Rapid Diagnostics* -immediate results: gives bacteria and resistance profile -proper antibiotic prescribed -low potential for resistance: because not given broad spectrum antibiotic
*KNOW* Bacterial Diagnostics
*Growth Conditions* -Different media types =Basic, Enriched, Selective, Differential, Anaerobic *Morphological Identification* -Microscopy and staining =Motility, Gram stain, etc. *Biochemical Testing* -Coagulase, oxidase, urease, etc. *Antigen Detection* -ELISA, IF, agglutination, EIA, etc. *Serological Diagnosis* -Antibody titer *Molecular Diagnostics* -FIH, PCR, RT-PCR, etc.
*KNOW* Host-directed Antimicrobial Therapy
*Organism Level* -targets the immune system -i.e. Vaccines *Cellular Level* -Targets individual cells -i.e. Macs -Modulation of bacterial entry -Limiting nutrients and resources -Enhancement of antimicrobial mechanisms
*KNOW* The Advantage of *Host-directed Antimicrobial Therapeutics* over Antibiotics
*Prevent or enhance bacterial uptake* -*Enhance* uptake when you have extracellular bacteria to destroy -*Inhibition* of uptake important when dealing with intracellular bacteria pathogens which need host *Enhance human cells to kill bacteria* -Directly activating the ability of the infected host cell to kill bacteria -Includes = activation of pathways that generate RNS and ROS, proteases, antimicrobial peptides, degrative proteins, etc. *Targets host resources essential for intracellular survival and replication of the pathogen* -Intracellular bacteria compete with the host cell fir nutrients and utilize host signaling and metabolic pathways -Therefore, targeting resources that are essential for intracellular survival and replication of pathogen can potentially compromise survival of the intracellular bacteria *Circumvent antibiotic resistance* -Killing intracellular bacteria without antibiotics because we are targeting the host, not the bacteria -but does it really work? *KNOW* Many of the identified host-directed antimicrobial drugs are effective against other intracellular pathogens
*KNOW* Antibiotic Surveillance and Assessment
*Purpose of Surveillance according to WHO* -"to better understand and respond to antimicrobial resistance patterns and key drivers, information about antimicrobial resistance incidence, prevalence, and trends" -Birds eye view/ broad view *Assessment* -encompasses diagnostic tools that identify resistance mechanisms and determine sensitivity to antibiotics -Close-up investigation of the mechanisms
*KNOW* Combination Therapies
*Resistance rapidly develops* against *compounds hitting a single target*, which automatically eliminates the vast majority of targets Combination therapies: 1) *Target same pathway* -Sulfamethoxazole/ Trimethoprim 2) *Inhibits AMR mechanisms* -B-lactams/ Clavams (tazobactam, sulbactam, avibactam) 3) *Enhance efficacy (Synergistic effect)* -Streptogramin A and B Screening for targets that enhance effectiveness of current antibiotics
*KNOW* GLASS Details
*Surveillance Site* -collects basic demographic, clinical, epidemiological, and microbiological information from patients *National Reference Laboratory* -promotes good lab practices and supports labs in national surveillance system *National Coordinating Center* -established and oversees the national surveillance program, gathers national AMR data and communicated with GLASS
*KNOW* Vaccines vs Antibiotics
*Vaccines* -Prevent a disease by targeting the immune system -Target the immune system -Long-term effect -Eradicate disease from society -No environmental pollution *Antibiotics* -Treat a disease by targeting the invading pathogen -Target the invading pathogen -Short-term effect -Increase virulence of diseases -Pollute the environment *Vaccines are not the answer for antimicrobial resistance* -But targeting the host and not the bacteria may be a solution
*KNOW* Asymptomatic Carrier
A person who carries an infective organism, but does not manifest any signs of infection -therefore, unwillingly spreads infection to other unaffected individuals
*KNOW* Scope of Search: Antimicrobial Peptides
Blood from lizards and reptiles Venom = peptide cocktail -Snake, spider, scorpion, bee, cone snail -Have thousands of different unique peptides that can be used in medicine -have antimicrobial peptides, just difficult to isolate them
Quiz 8: What does CLSI stand for?
Clinical and Laboratory Standards Institute
*KNOW* Secondary Metabolites
Compounds that are not required for normal growth or proper "primary" functions of the organism
*KNOW* Metal-mediated Inhibition
Copper (Cu) and Gallium (Ga) Ga disrupts bacterial ion metabolism by being taken up instead of iron Lethal dose of Cu ions interferes with normal cell functions and membrane integrity
Members of WHO
Divided into 6 regions -Africa -Americas/ Pan-America -Eastern Mediterranean -European -Southeast Asia -Western Pacific Antibiotic surveillance on global scale is an extremely challenging task
*KNOW* Vaccines
Do not target the infectious agent, but the immune system -Stimulates the immune system to prevent any future infections -Vaccines = Immunostimulants *Prophylactic Vaccines* -Stimulates the immune system to prevent infections *Therapeutic Vaccines* -Stimulate the immune system to treat disease -slow-progressing disease, i.e. cancer
*KNOW* Species-specific Compounds
Early screening for TB drugs identified mainly species-specific drugs HTS can enhance the discovery of species-specific compounds Whole-genome sequencing of resistant mutants can identify antibiotic targets Rapid diagnostics can identify resistant isolates
Quiz 8: Which of the following is a combination of diffusion and dilution method?
Epsilometer Test
*KNOW* Diffusion/Dilution: E-test
Epsilometer Test Combines both *diffusion and dilution methods* *Quantitative method* to assess antibiotic sensitivity -as concentration gradient of antibiotic increases, zone of inhibition increases (is a strip that ahs different concentrations of antibiotic) -MIC = concentration of antibiotic required to completely inhibit bacterial growth
*KNOW* Examples of plant derived drugs
Etoposide - Cancer Scopolamine - Motion sickness Vinblastine - Cancer Morphine - Analgesic
*KNOW* PACCARB Recommends
Expand, Standardize, and Improve delivery of infection prevention and antibiotic stewardship education and training at all levels of the healthcare workforce *Recommendation 1* -Required education and training accrediting bodies to include a model curriculum in IP&AS that is taught at all levels of healthcare and continuing worker education -Incorporate existing recommended core competencies *Recommendation 2* -Highlight hand hygiene in curricula at all levels of training as foundational requirement for successful infection prevention -Recognize and apply successful tactics for achieving high hand hygiene compliance in healthcare settings
Quiz 8: AMR surveillance is easy at the national level but becomes challenging at the global level. True/False
FALSE -AMR surveillance is hard at BOTH the national and global level
Quiz 8: GLASS collects information on both viral and bacterial infections. True/False
FALSE -GLASS collects basic demographic, clinical, epidemiological, and microbiological information from patients to get data on AMR and make informed decisions
Quiz 9: Host-targeted antimicrobials have a very high specificity in killing bacteria (i.e. only target certain bacterial species). True/False
FALSE -Host directed antimicrobial therapy targets individual host cells like Macrophages -does not have high specificity for killing bacteria, because host is killing the bacteria with immune system
*KNOW* GLASS Goal
GLASS = *Global Antimicrobial Resistance Surveillance System* by WHO Goal: -"to enable standardized, comparable and validated data on AMR to be collected, analyzed and shared with countries, in order to inform decision-making, drive local, national, and regional action and provide the evidence based for action and advocacy"
*KNOW* Early Vaccines
Small pox was wiping the population of Earth as soon as it appeared until no other victims were able to carry it In China, people realized survivors were immune to subsequent exposure of smallpox Doctors took small samples of scab from smallpox patients -ground it into a fine powder and blew it into the noses of healthy individuals Arab physicians used a similar approach -made small incision onto a person's skin and rubbed a wound swab from a smallpox patient *In both cases, people became immune to smallpox*
Quiz 8: The majority of bacterial operons that code for secondary metabolites is not expressed under normal laboratory conditions. True/False
TRUE
Quiz 8: AMR develops faster when a single drug is used. True/False
TRUE
Quiz 8: It is estimated that only 1% of all bacterial species is culturable under laboratory conditions. True/False
TRUE
Quiz 8: It's estimated that over 60% of antibiotic prescriptions for respiratory issues are unnecessary. True/False
TRUE
Quiz 9: Metal surfaces (i.e. copper) can kill bacteria on contact. True/False
TRUE
*KNOW* Targeting Host resources required for survival of Intracellular Bacteria
Targeting host resources *CAN* inhibit infection
*KNOW* Hight-throughput Screening (HTS)
The rules of penetration will enable building focused libraries for discovering anti-infectives and will revive HTS platform *Lipinski's Rule of 5* Guidelines = in order for a *molecule to reach a specific target in the body*, must have the following: -1) MW< 500Da -2) H-bond Donors < 5 -3) H-bond Acceptors < 10 -4) Octanol water partition coefficient < 5 -measures how water loving the molecule is -provides the chance a molecule will penetrate the cell membrane
*KNOW* Silent Operons
The majority of bacterial operons coding for *secondary metabolites are silent and not expressed in vitro* -turning on silent operons can provide important advancements in hunt for novel antibiotics An efficient approach for turning on is yet to be developed Combined with rapid dereplication, expression from *silent operons would enable novel discovery platform*
