exam 1 Flashcards
Bacteriostatic
drugs that keep bacteria in the stationary phase
Bacteriocidal
drugs that kill bacteria cells
Beta lactams
a class of antibiotics that are active cell wall agents through the inhibition of transpeptidases and transglycosylases which function to build/maintain murein (peptidoglycan), cause cell membrane extrusion and disruption- bacteriocidal
Include Penicillins, Cephalosporins, and Carbapenems
Penicillins
A beta lactam that primarily functions to destroy Gram positive microbes, with much better activity against anaerobes
Ampicillin has added activity against a few gram negative aerobes and peperaciliin has yet more added gram negative coverage
Beta-lactamase inhibitor
added to some beta lactams to broaden the spectrum of impact. Competitively inhibit some beta-lactamse enxymes that confer resistance
Ex: Amoxicillin + Clavulanic Acid
Ampicillin and Sulbactam
Cephalosporins
a class of beta lactams with a spectrum of activity that varies by generation. 1st generation is gram positive with very few gram negative. With each generation increasing spectrum increases to be more gram negative and less gram positive
Cefazolin & Cephalexin
beta lactams, 1st generation cephalosporins that have high impact to gram + and very few gram -
Cefoxitin & Cetotetan
beta lactams, 2nd generation cephalosporins that have medium impact to gram + and more impact to gram -
Ceftiofur & Ceftazidine
beta lactams, 3rd generation cephalosprins that have less impact to gram + and more impact to gram - than generation two
Carbapenems
beta lactams that are used with huge restriction, called the big guns
Imienem and Meropenem
Potent- 4 quadrant activity
Limited veterinary medicine use because of antibiotic resistance worry
Sulfonamides
DNA synthesis inhibitors that work through inhibiting folate biosynthesis through dihydropterate synthesis
Include Sulfadimethoxine and Sulfamethoxazole, which are bacteriostatic unlss they are combined with Trimethoprim
Trimethoprim
Combined with Sulfonamides (Sulfadimethoxine/ Sulfamethoxazole) to allow them to be bacteriocidal
Targets both + and - but very strongly aerobes
Not practically useful for anaerobes
Nitroimidazoles
A DNA synthesis inhibitor that acts through strand breakage (bacteriocidal) Spectrum: Only works on anaerobes and some protozoa- can be gram + or -
off limits to food animals
Metronidazole
a nitroimidazole, which acts as a DNA synthesis inhibitor through strand breakage. only works for anaerobes (gram + or -) not for use on food animals
Fluoroquinolones
A DNA synthesis inhibitor that acts through DNA gyrase and topoisomerase IV (enzymes that unwind DNA for replication) - Bactericidial
strong activity against gram - aerobes only and also some mycoplasma species activity
include Enrofloxacin, Danofloxacin, and pradofloxacin
Protein Synthesis Inhibitors
Act to inhibit protein inhibitors either through the small 30S subunit, large 50S subunit or complete 70S ribosome
All are bacteriostatic except for Aminoglycosides (gentamicin)
Aminoglycosides
A protein synthesis inhibitor that acts to prevent binding to the 30S small ribosomal subunit. Include gentacin and Amikacin. Since its uptake into the cell is oxygen dependent, only works on aerobes and best on gram negatives
Macrolides/lincosamides
protein synthesis inhibitors that act through the 50S large subunit to prevent transpeptidation
spectrum varies by agent but generally doesnt work well on gram negative and much better from gram positive, stronger on gram positive aerobes
some activity against mycoplasma
Erythromycin and clindamycin
Acetamides
protein synthesis inhibitors that act through the 50S large subunit to prevent transpeptidation- bacteriostatic
also called phenicols
Chloramphenicol and Florfenicol
Has activity in all 4 quadrants
Chloramphenicol also has mycoplasma spp activity
Tetracyclines
prevent binding to 30S small ribosomal subunits - bacteriostatic
includes Chlortetracycline & Florfenicol
have activity in all 4 quadrants and mycoplasma spp activity
What species have activities against mycoplasma spp.
Tetracycline, Chloramphenicol, Fluoroquinolones, and some macrolides
Acquired Resistance
resistance gained due to the acquisition of exogenous genes via mobile DNA elements or mutations
Mobile elements can be incorporated through
a) Free DNA transformation –> recombination
b) Bacteriophage Transduction and transposable element to transpostion
c) plasmid conjugation–> transposition and recombination
mechanisms of resistance to antibiotic
-Drug can be inactivated by acquired bacterial enzymes ex: beta lactamses
-Modification and changes in drugs targets. example: if DNA gyrase mutation acquired- fluoroquinolones cant bind
-Changes that prevent access to the cell like mutations in transmembrane proteins changes
-efflux pumps: changes in transmembrane proteins that can export the drug out of the cell
Intrinsic resistance
resistance due to inherent metabolic attributes of the organism
MRSA/MRSP
Methicillin resistant staphylococcus/pseudointermedius –> resistance to all beta lactams including carbapenems
ESBL
extended spectrum beta lactamases produced by gram negative bacteria that confer a resistance to pencillins and almost all cephalosporins
CRE
Carbapenem Resistance Enterobacterials
enteric gram negatives that are resistance to all beta lactams
VRE
Vancomycin-Resistance Enterococci-
Not an issue in vet med
Antimicrobial Susceptibility Testing (AST)
Used for only clinically significant bacteria isolated in culture. By acquired resistance might be different en-vivio than in-vitro
method can be selected by laboratory and influences by caseload/budget and organism tested (both valid for many drug and microbe combination
Broth microdilution
used to find the minimal inhibitory concentration
tubes inoculated in Mueller-Hinton broth with antibiotic, finding the lowesdt dilution with no visible growth
Compare to breakpart values to interpret if the animal susceptible, intermediate, or resistant
How are breakpart values determined?
Committees develop cut offs/breakpoints with the knowledge of drug dist. and effects on bacteria, clinical trials, and distributions of 100s of clinical bacterial isolates
Kirby-Bauer Disc Diffusion
a proxy for arriving at same S, I, R interpetations
As MIC increases, there is more resistance, and there is a smaller zone of inhibiton present
Zone of inhibition also compared to published standards
Cryptic
phenotypically silent DNA sequences not typically expressed- much of the bacterial plasmid DNA
Conjugate plasmids
some plasmids that are transmissible among bacterial cells
Operons
the gene organization of prokaryotes where mRNA is transcribed in tandem under the control of the same promoter and multiple genes are expressed by coding gene
How to prokaryotes divide?
through binary fission
What ribosomes do prokaryotes have?
70S ribosomes
What allows gram positive bacteria to take the dye?
crystal violet is taken up and not removed through the decolonizer
Peptidoglycan (murein)
crosslinked polymer with repeating subunits of N-acetyl glucosamine and N-acetyl muremic acid, 80% of the mass of bacteria
Crosslinked by transpeptidases and transglycosylases
How do gram + and - differ
gram - bacteria have a much thinner cell wall and an outer bilpid membrane. Are unable to take up the crystal violet stain
How is the prokaryote cytoplasmic membrane held together?
through noncovalent forces, there are nochemical bonds present
Sporulation
a specialized form of cell division that some bacteria can do where the parent cell dies
more common in gram + bacteria species
spores are more resistant to heat, UV radiation, desication, and antimicrobial disinfection
Obligate intracellular bacteria
an organism that needs to be within another cell for replication
Mollicutes
organisms with no cell wall and therefore a gramstain does not work on them, antibody stain is needed for detection
seen in Mycoplasma species
Isolate
individual organism isolated in pure culture
Strain
descendant of single isolate
Ex: sterne strain of anthrax is used in vaccines because it less likely to cause disease
Heterotrophs
organisms that are able to assimilate carbon from outside for energy and growth
Capnophilic
microbes that require CO2 but not for energy through photosynthesis but for certain metabolic pathways
How are bacteria able to produce ATP?
ATP is generated through ATP synthase powered by the electron transport chain on their plasma membrane
electron acceptor varies depending the conditions of the organism
Obligate aerobes
microbes that must use O2 as there electron acceptor for ATP production
have no enzymes for dealing with O2 radicals
Anaerobes
microbes that typically use sulfate (SO4) as their electron acceptor for ATP production. O2 is toxic to them
Facultative Anaerobes
microbes that prefer to live as anaerobes but can respire aerobically if O2 is present. Common among pathogens
Aerotolerant anaerobes
dont use O2 to make ATP but can survive in presence of superoxide dismutase and peroxidase, dont have catalse for full antioxidant properties
Facultative anaerobes
Have Catalse, SOD, and peroxidase for the elimination of oxygen radicals and therefore can live in conditions with oxygen
Koch postulates
1) Microbe must be found in abundance of all organisms suffering disease and shouldnt be in healthy organims
2) Microbe must be isolated from diseased organism and grown in pure culture
3) Cultured organism should cause disease when introduced to healthy organism
4) Microbe must be reisolated from inoculated diseased host and identical to the specific causative agent
Nonsterile sites
mouth, lower urinary tract, skin
Sterile sites
joint spaces, abdominal fluid, urinary bladder, blood (usually), brain, and CSF
Exotoxins
Produced by both gram + and - bacteria
Diffusible (can effect distant targets)
Proteins or polypeptides
Produce a pharmacologically specific effect
May be lethal in minute amounts
Labile to heat and chemicals
COnvertible to toxoids
Ex: CLostridium tetani
Endotoxins
Part of the gram - cell wall
LPS is a toxic component
Produce many effects based on host responses
All similar structure across gram - bacteria
Lethal in heath and chemical
Not converitble to toxoids
O-specific side chain
A repeating sugar molecule that is highly variable
on the lipopolysaccharide
Lipid A
the toxic portion of the endotoxin (lipopolysacchride)
that bind to the toll-like receptor 4 (on macrophages) for potent activation
Endotoxemia
a clincal condition by a high concentration of endotoxin in the blood leading to fever, hypotension, and leukopenia
Colonization
successful multiplication of microbiota at an anatomic site
Contamination
Mechanical transfer of microbiota to an anatomic site. little to no multiplication involved
Infection
invasion of tissue paired with host response, previous colonization is not required
Transient Microbiota
colonizes the superficial layers of the skin, may be opportunistic pathogen and even primary pathogens
1) can convert components of ingesta to nutrients
2) colonization of resistance to pathogens
3) keep immune response in balance
How can transient microbes help with resistance to pathogens
competing for nutrients, regulating the pH, and producing bacteriocins or antimicrobial peptides
Saprophytes
environmental organism that grows on decaying organic matter
Commensal
organisms that colonize tissue without disease but may act opportunistically
Symbionts
colonize host tissue but mutually beneficialy relationship exists
opportunists
colonizing host tissue but cause disease with tissue injury or environmental change
primary pathogens
infection directly causes disease but host species predilections may occurs
Indirect methods of bacterial disease detection
Detection of the host antibody direction against a bacterial or fungal antigen
Has animals immune system seen this antigen? Concern with vaccination as it might detect the vaccination
Stationary phase
the phase in microbe development where capacity has been reached as nutrients are exhausted or there is a build up of toxic metabolites and inadequate pH level
How mich bacterial culture in-vitro differ from en-vivo?
There is no innate+adaptive immune system, physiological clearance mechanisms or bacterial quorum sensen
Quorum sensing
Quorum sensing is the regulation of gene expression in response to fluctuations in cell-population density
Non-selective growth medias
growth medias where nothing is added to inhibit or favor a particular microbe’s growth
example: blood agar
Selective medias
growth medias with additives to inhibit specific groups of microbes to aid isolation from heavily colonized or contaminated body sites
Ex: MacConkey agar and Phenylethyl Alchol Agar
Differential medias
medias with additives to aide in the differentiation of growth (carbon sources or pH indicators)
Ex: MacConkey agar
MacConkey Agar
a specific media that is both Selective (permits growth of gram negatives) and Differential (pH indicator for determination of lactose fermentation)
What color does the MacConkey agar change if lactose fermenters are present
lactose fermenters lower the pH and turn the media pink
MALDI TOF
a predominant method of identification, compares the weights of proteins to a databse via mass spectometry
Immunodiagnostic testing
almost all detect host antibody (ELISA, AGID, Agglutinati tests, fluorescent AB test, indirect immuno Assay)
PCR
a form of molecular detection where you need to know what youre looking for, good for difficult hard to cultivate agents, sometimes more sensitive than culture, can be be expensive
Rapid
Enterotoxigenic E. Coli (ETEC)
msot common cause of E. Coli diarrhea in farm animals
Have fimbriae to faciliate the attachment to epithelial cells
and enterotoxins that cause fluid loss without inflammation preented with good hygiene, adequate colostrum transfer
treated with fluid therapy and bottle feeding
LT (heat-labile toxin) and STa (heat stabile toxin A)
enterotoxins produced by Enterotoxigenic E.Coli that lead to secretory diarrhea through the active secretion of Cl-, the impaired absorpotion of Na+ which drives water flow
STb (heat-stabile toxin B)
an enterotoxin that works indirectly through enteroendocrine cells, promotes the secretion of serotonin and vasoactive intestinal peptide
Shigatoxigenic E. Coli (STEC) ad Enterohemorrhagic E. Coli (ETEC)
Infect through LEE: locus of enterocyte effacement which allows attachment to the host epithelial cells through intimin attachement and a type III secretion which introduces genes for pedestal formation for bacteria
cause diarrhea
Edema disease
A disease caused by STEC that mainly affects weaner pigs. Causes edema of the eyelids, face, subserosal stomach, meninges, and other organs, leading to heath
Adults are a resevoir for spread to weaned pigs
Virulence factors in STEC
LEE (locus of enterocyte effacement leading to attachment and formation of bacterial pedestals)
Stx toxins: Cytotoxins that inhibit protein synthesis and induce apoptosis
Hemolysis: aids surival of STEC in intestine by releasing iron
Acid resistance: enhances the survival in the stomach and low infectious dose
EPEC
attaching and effacing E. Coli that affects all animal species via locus of enterocyte effacement with intimin causing cytokskeleton changes in enterocytes lading to diarrhea pathogenesis and malabsorption
Invasive and Adherent E.coli of Boxers and french bulldogs
Bacteria that impacts Boxers and Frenchbulldogs leading to granulomatous colitis from an intracellular E. Coli infection. Not regarded as contagious and clinical manifestations are simiular to Crohns disease
ExPEC
Extraintestinal Pathogenic E. Coli leading to a wide range of infections (UTI, mastitis, colisepticemia)
Frequently causes septicemia in neonates
Translocation across GI mucosa to access the circulation , leading to septic shock causing a massive systemic infection response to LPS that can lead to emoblization in various body sites
How can you diagnose ETEC
PCR for genes fro toxins (STa, STb, LT)
Culturing on MacConkey agar (lactose fermenter and easy to grow)
How can you diagnose STEC
Hard to diagnose because there are other causrs for diarrhea (Rotavirus) but could use clinical signs to diagnose Edema Disease
Culturing on MacConkey agar (lactose fermenter and easy to grow)
How can you diagnose EPEC
very challenging would need to do histopathology for the attaching and effacing lesion
Culturing on MacConkey agar (lactose fermenter and easy to grow)
Shigella spp.
Species that only cause disease in primates and very closely related to enteroinvasive E Coli
cause severe dysentery
How can E. coli caused diarrhea be managed?
Prevented using colostrum management, Oral K99 antibodies for ETEC and hygiene
Treated with aggressive fluids, antibodies (colisepticemia)
How can septicemia be diagnosed and then treated
antimicrobial susceptibility, IgG measurement for the failure of passive failure, aggressive IV fluid management, anti-inflammatories and steroids
Salmonella
a gram negative rod that is a facultative anaerobe and intracellular, nonspore former, can be motile/non motile
Salmonella enterica
Spread through fecal-oral, foodborn, transovarial, colostrum
enters through bacterial-mediated endocytosis through the invasion of interestinal epithelium (primarily M cells) Type III secretion system to induce cytoskeleton changes and the mammalian cell engulfs the bacteria (phagosome)
Host restricted
a bacteria that is restricted to a particular host
Host adapted
a bacteria that colonize host species as primary resevoir but also can colonize other species
broad host range
bacteria that can infect anyone ex: Tymphimurium
Salmonella enterica
