L.39- Controlling Bacterial Infections

if direct contact with infectious agent is known or suspected, _ is the most effective way to prevent transmission of infectious agent

hand washing

_ of infectious agents is one of the most common and problematic sources by which infectious agents are transmitted from person to person

carriage

artificial agents to kill or slow growth of microbes

chemicals, detergents, synthetic drugs

natural agents to kill or slow growth of microbes

antimicrobial drugs, natural acids, alcohols

use of antimicrobial drugs must take into account toxicity of agent to _

humans

antimicrobial agents used only externally on inanimate objects

disinfectants, sanitizers

antimicrobial agents used externally on body surfaces

antiseptics, germicides

antimicrobials that are safe to ingest or inject

antimicrobial drugs (antibiotics, antifungals)

substances that inhibit or kill growth or replication of microbes or viruses

antimicrobials

_ antibiotics lyse and kill bacteria

bactericidal

_ of bacteria can result in worse disease consequences due to release of endotoxins or other toxins

lysis

_ antibiotics slow/stop bacterial growth but bacteria are not killed

bacteriostatic

ideal antibiotic target is molecular component of bacterial cell that is required for bacterial _ or _

proliferation, survival

if antibiotic target is found in _, then inhibition of target must not have harmful effect

host

insatiable public demand for antibiotics contributes to antibiotic _

resistance

poor stewardship of antibiotic administration by medical community contributes to antibiotic _

resistance

outer membrane of _ bacteria can serve as effective barrier against antibiotics

gram negative

microbes can circumvent antibiotic penetration by changing their _ or size of _ in membrane

membranes, porins

bacteria have ATP-dependent _ to remove antibiotics that enter cell so antibiotic doesn't accumulate to high concentration within cell

efflux pumps

bacteria with efflux pumps are still sensitive to antibiotics but much _ concentration is required for effectiveness

higher

some efflux pumps have narrow _

specificity

efflux pumps with _ specificity can confer multidrug resistance

broad

example of antibiotic _ is not growing in the presence of antibiotic where antibiotic only works via killing growing bacteria

tolerance

for some bacteria, especially in _, certain percentage of population is dormant (not growing)

biofilms

dormant cells are called _ and contribute to high level of antibiotic tolerance observed in biofilm-forming bacteria

persisters

some bacteria produce enzymes to inactivate antibiotic activity by _ it or modifying it with different _ that reduce its activity

hydrolyzing, functional groups

microbe usually acquires gene whose product modifies/inactivates drug via _

horizontal gene transfer

some bacteria can _ target protein or acquire enzyme that modifies it so drug no longer binds or has reduced binding affinity with target

mutate

_ in bacterial proteins (antibiotic targets) are the primary mechanism of antibiotic resistance

point mutations

for antibiotics requiring _ to exhibit their biological activity, mutations can occur that decrease/eliminate expression of a certain enzyme

activation

_ bacteria can acquire mutations that reduce expression of flavodoxin/ferredoxin that are required to activate metronidazole

anaerobic

rate of antibiotic resistance and spread of occurrence is accelerated by _ and _ of antibiotics in people and animals

inappropriate use, over-use

initial search for new antibiotics involving screening for antibiotic activity in large quantities of bacteria/fungi from soil/environmental sources

high-thoroughput screening methods

major limitation of _ is that naturally-occuring antibiotics are almost all products of secondary metabolism and are often regulated in response to environmental stress or competition with other microbes

high-thoroughput screening

modern modification approach to generating antibiotics takes advantage of _ chemistry

combinatorial

_ chemistry involves screening library of compounds made from randomly modifying core "lead" structure with large bank of chemical groups to make new compounds

combinatorial

_ chemistry introduced notion that compounds can be synthesized as mixtures and screened for antibiotic activity as mixutres

combinatorial

drug _ is application of known drugs/compounds to treat new disease

repurposing

significant advantage of _ is that since the drug has already passed a number of toxicity and other tests, its safety is known and risk of failure because of adverse toxicology has been reduced

drug repurposing

combination therapies _ cells so additional compound can be more potent

chemosensitize

_ therapies increase efficacy by lowering doses of each antibiotic to minimize toxicity in host

combination

_ therapies minimize possibility for development of drug resistance

combination

_ therapies involve screening for components of existing antibiotics that make them more potent, stable, and effective

augmentation

an example of a(n) _ is clavulanic acid being used with other lactams to prevent their degradation

augmentin

_ is based on use of structure of target protein to design drug that binds to functionally important or essential sites on target biomolecule to block normal activity of target

rationale drug design

functionally essential sites on target biomolecules are _ likely to undergo mutation because of importance of maintaining normal physiological function

less

rationale drug design requires _ structure of target protein and additional structures of target protein with substrates/interacting partners in complexes to act as template

cystal

_ uses completed genome sequence of pathogens and their avirulent counterparts to identify genes that encode novel bacteria-specific target proteins

functional genomics

_ is based on the concept that genome sequencing information allows identification of many unique aspects of bacterial metabolism and physiology

functional genomics

enzymes unique to pathways should be _ to new rationally-designed antibiotics that target them

vulnerable

inhibitors of _ pathways could block up-regulation of virulence genes in response to population density

quorum sensing

living organisms that when administered to host can confer a health benefit

probiotics

_ take advantage of the idea that "good" resident microbiota may out-compete undesirable pathogens

probiotics

_ are of particular interest for diseases classified as polymicrobial or community-based or microbial shift diseases

probiotics

_ reintroduce missing "good" bacteria by oral intake

probiotics

bacteriophage therapy takes advantage of _ and _ of bacteriophages to attack only bacteria that possess receptors for that type of bacteriophage without harming bacteria within normal microbiota

killing power, specificity

antibiotics target processes within bacteria essential for _ or _

growth, viability

emergence of antibiotic-resistant bacteria within a microbial population that had been exposed to antibiotic can best be described to be a result of _

depletion of antibiotic-sensitive microbes and proliferation of antibiotic-resistant organisms

_ of an antibiotic refers to where the antibiotic is distributed in body

bioavailability

the manner by which the body expels the antibiotic from the body

rate of excretion

3 factors that influence the effectiveness of any antibiotic that can be taken orally

bioavailability, rate of excretion, stability

phage-mediated lysis of bacteria in bloodstream could potentially release pro-inflammatory _ and _ fragments into bloodstream which could result in toxic shock and potentially death

endotoxin, cell wall