Gram (+) Bacilli Flashcards
List the gram (+) bacilli (8)
Bacillus anthracis Bacillus cereus Clostridium tetani Clostridium botulinum Clostridium difficile Clostridium Perfringens Corynebacterium diphtheriae Listeria monocytogenes
What does Bacillus anthracis look like?
Large gram (+) rods in chains
What is Bacillus anthracis’ capsule made out of?
Protein - Poly D glutamate
Black eschar
Black, necrotic cutaneous lesion with surrounding erythematous ring
Caused by Lethal Factor (LF) of Bacillus Anthracis
Bacillus Anthracis respiration
Obligate aerobe
Bacillus Anthracis transmission
BA is spore forming. It hibernates in a state with low metabolic activity.
Bc of it’s tough coat it can survive in many environments and withstand temp changes
Spores are small and tough. They grow back into metabolic state when environment is favorable.
The 2 toxins produced by bacillus anthracis
Lethal Factor and Edema Factor
Lethal Factor (LF)
toxin produced by Bacillus anthracis
Symptoms will not be caused unless Edema factor is ALSO present
Exotoxin that acts as a protease and cleaves MAP Kinase.
MAPK is a signal transduction protein involved in the control of cell growth.
LF leads to tissue necrosis (black eschar)
Edema Factor (EF)
toxin produced by Bacillus anthracis
Symptoms will not be caused unless LF is ALSO present
It’s an adenylyl cyclase that raises cAMP intracellularly
The higher cAMP causes fluid to move into extracellular space, causing edema.
Edema limits host defenses and indirectly prevents phagocytosis.
What are the 2 bacterial groups that form spores?
Bacillus and Clostridium
Pulmonary anthrax
Wool-Sorter’s Disease
Spores last a long time so they can get into soil/wool and stay there. When people handle the wool, they inhale the spores which germinate in the lungs.
Causes mainly pulmonary symptoms
Starts out with nonspecific symptoms like cough. You must catch and treat early bc it quickly progresses to mediastinal lymph nodes.
Symptoms quickly progress to hemorrhagic mediastinitis, which is a pulmonary hemorrhage. It is close to 100% mortality when pulmonary hemorrhage is seen.
Chest XR shows widened mediastinum
Tx for anthrax
Treat early
Fluoroquinolones
Doxycycline (2nd choice)
Bacillus cereus respiration
Obligate aerobe
What is bacillus cereus infection most associated with?
Food poisoning!!!
Someone who comes in with vomiting or diarrhea after eating reheated fried rice.
Reheating triggers germination of the spores and toxin formation.
Clostridium respiration
obligate anaerobes
Clostridium tetani transmission
Often found in soil, but tetani needs to get under skin into anaerobic environment to cause infection. Ideally, it gets in through a puncture wound that’s been closed off to air (rusty nails, barbed wire)
Foreign object with tetani punctures body. Spores embed in flesh, vegetate and stay at wound site. Produces toxin (Tetanus Toxin/Tetanospasmin). The toxin causes the symptoms.
Neuromuscular symptoms of tetanus
Spastic paralysis (relentless muscle contraction leading to rigidity)
Rhesus sardonicus - an evil grin or Lock Jaw symptoms (tense masseters prevent jaw from opening)
Opisthotonus - Extension/arching of back due to strong spasms of back muscles.
Tetanus toxin mechanism
Tetanus toxin (Tetanospasmin) is from C.tetani
Tetanus toxin travels retrograde from the motor axons to the spinal cord
Acts as a protease. It cleaves SNARE proteins which inhibits exocytosis of neurotransmitters into synapses.
Cleavage of SNARE inhibits release of GABA and Glycine from Renshaw cells (normally these guys are inhibitory nt’s)
This leads to uncontrolled neuronal firing leading to spasms.
Tetanus vaccine
Toxoid vaccine - it’s a toxin conjugated to a protein to increase immunogenicity. This causes antibody responses to the toxin, but not to the bacteria.
How is Clostridium Botulinum transmitted?
Through improper canning of foods
Improper/insufficient heating cycles when canning allows spores to survive. They then germinate and thrive in the anaerobic environment of the sealed can and make a ton of heat-stable toxin.
“A couple of family present with very similar symptoms (neuro symptoms)” - May have shared the same food!
Clostridium Botulinum symptoms
Flaccid paralysis - going limp. Tough to keep body upright.
Caused by absence of muscle contraction
A descending paralysis (starts superiorly and goes down - NOT like Guillen-Barre)
First symptoms may be eye symptoms - Diplopia and ptosis
Clostridium Botulinum toxin mechanism
The preformed toxin is absorbed in the gut and travels to peripheral nervous system via blood to cause symptoms
It only affects PNS, bc it CANNOT CROSS BBB
Toxin cleaves SNARE protein, which prevents fusion of vesicles with presynaptic nerve terminals (just like tetanus). The difference is that Botulism attacks motor neurons that release ACh. Ach normally excites and its release causes contractions. Its absence means no contractions which means flaccid paralysis.
What is the difference between Botulinum toxin and Tetanus toxin?
The target:
Tetanus = GABA, Glycine releasing cells - spastic paralysis
Botulinum = ACh releasing cells - flaccid paralysis
Floppy Baby Syndrome
Clostridium botulinum infection in babies.
Causes same flaccid paralysis, but the ingestion of the toxin is different.
Adults do not normally get sick from ingesting spores (we need the preformed toxin to get sick). The bacteria itself is weak.
In babies, they do not have robust GI flora yet. They have a perfect anaerobic environment without competition. Spores can germinate and produce toxin in babies.
The spores are normally ingested from honey. Infants should avoid honey.
Infantile botulism is more common than adult botulism
What are the 2 toxins produced by Clostridium difficile?
Exotoxin A - binds to brush border enzymes of intestines and causes inflammation, cell death, and watery diarrhea
Exotoxin B - depolymerizes actin to disrupt cytoskeleton integrity. Leads to enterocyte death and necrosis. Leads to yellow-ish gray exudate that forms a pseudomembrane that covers the colonic mucosa (pseudomembranous colitis)
When do people typically contract a C. diff infection?
It’s a nosocomial diarrhea. People get it while hospitalized.
Spores are easily transmitted patient to patient without proper precautions (make sure to wash hands with soap and water…wiping shit down alone doesn’t do enough here)
C.Diff does not compete well with normal flora (like botulinum), but many patients in the hospital are on antibiotics so… that’s a problem
Common antibiotic that predispose to C.Diff is Clindamycin (Clinda + poor hand washing = copious diarrhea)
Which antibiotic is most associated with C. diff infection?
Clindamycin (also Ampicillin)
How can we know if diarrhea is from C.diff vs something else?
2 ways:
1) Visualize the pseudomembranes directly (histo/endoscope)
2) Look for toxin in stool with assays (PCR). We are looking for toxin in the stool, NOT the microbe.
1/3 of hospital pts are colonized for C.Diff (not that many infected) so bacteria in stool is just meh.
Tx for C.Diff infection
Oral Vancomycin (not absorbed well in gut so it stays there to do its thing) - oral also lowers the typical side effects of vanco. IV is not useful.
OR
Metronidazole
Which Clostridium species is most associated with motorcycle accidents or deep penetrating wounds from military combat?
C. Perfringens
Both scenarios are instances where large amounts of flesh are exposed to dirt/dust - this is important bc C. Perfringens is spore forming and therefore likes the dirt/soil
Gas Gangrene
One of 2 diseases classically caused by C. Perfringens
“Claustridial myonecrosis”
When claustridium enters the wound and causes infection a gas is produced under the infected tissue.
This presents as crepitus (crackling sound on palpation)
Gas is produced as organism consumes carbs.
The myonecrosis is due to an alpha toxin called Lecithinase that cleaves lecithin (a phospholipase) and damages cell membranes.
Lecithinase causes RBC hemolysis if RBC membranes are affected. On blood agar, it forms a double zone of hemolysis
You need to plate C. Perfringens in anaerobic environment (this should give it away in the question)
Tx = IV Penicillin G
What toxin causes Gas Gangrene?
Lecithinase from C. Perfringens
How do you treat Gas Gangrene?
IV Penicillin G
Describe the food poisoning associated with C. Perfringens?
One of the 2 major illnesses linked to C. Perfringens
Causes a late-onset watery diarrhea.
Food poisoning is the result of ingesting a large amount of spores that must germinate in gut and then produce toxin (that’s why it’s not immediate).
Does not usually require an antibiotic - it’s a transient infection like most diarrheas.
Unique bc all others needed a preformed toxin to infect adults. C. Perfringens does not.
What does cornybacterium diphtheriae look like?
Club shaped
Metachromatic granules that stain with aniline dye like methylene blue or toluidine blue (red granules with rest of cell blue)
V or Y formation
Diphtheria toxin
an exotoxin secreted by corynebacterium diphtheriae
Has 2 subunits: Subunit A = active. Subunit B = Binding.
Toxin causes ADP-ribosylation of elongation factor 2. This inhibits ribosome formation and therefore protein synthesis. This leads to cell death and formation of pseudomembranes (thick grayish exudate over mucosa of oropharynx)
Throat and tonsils bc the infection is transmitted through respiratory droplets.
Colonizes oropharynx and can spread to larynx and trachea causing airway obstruction.
Can cause lymphadenopathy that looks like a characteristic neck thickening (Bulls Neck)
What happens if diphtheria toxin makes it into blood?
Systemic effects in heart and NS
Life threatening myocarditis - presents with arrhythmias and heart block
Local paralysis beginning in posterior pharynx and may lead to other cranial nerve issues - caused by toxin damaging myelin of nerve fibers
How do you diagnose a diphtheria infection?
Definitive dx requires a culture or a toxin assay
Swab grayish membrane and plate them in 2 special agars:
Tellurite agar
Loeffler’s Medium
In vitro assay on filter paper that has anti-toxin on it. If toxin binds to it there’s a rxn and we can say we have a toxic strain: Elek’s Test.
Elek’s Test
Assay to determine Diphtheria infection
What special agars are used to plate Corynebacterium diphtheriae?
Tellurite Agar and Loeffler’s Medium
Diphtheria vaccine
Toxoid vaccine - inactivated toxin bound to protein.
Given routinely in USA.
Often given with tetanus toxoid and acellular pertussis vaccine in TDaP
Produces powerful IgG response
How do you treat a patient with diphtheria who was never vaccinated?
Passive immunity via anti-toxoid
Look out for patients who are immigrants! Kids are not vaccinated from many countries
Listeria hemolysis
Narrow zone. B-hemolytic.
Listeria respiration and motility
Facultative intracellular - can live and reproduce inside and outside of cells.
When it’s outside of cell, it uses its flagella for motility - It has “tumbling motility” extracellularly
Inside the cell it rapidly polymerizes actin against the bacterial wall so it’s propelled in opposite direction. They can even jump cell to cell like this - “Actin rockets”
What environments are associated with Listeria?
Cold environments. It survives and multiplies in near-freezing temperatures.
What food items are typically associated with Listeria contamination?
Unpasteurized milk
Packaged meat
Soft Cheeses
Who is most at risk of contracting a Listeria infection?
Pregnant women are 20x more likely to get Listeria infections. They make up most cases. Infection early on can lead to termination of pregnancy. Later term infections lead to disease in the newborn.
Pregnant women shouldn’t eat soft cheeses.
Listeria is 3rd most common cause of meningitis in newborns (GBS, E Coli)
Listeria can also cause meningitis in elderly > 60
Who is at risk of developing meningitis from Listeria?
Newborns, Older adults (>60)
Tx for Listeria
Ampicillin
Tx of meningitis in adults normally is vancomycin and cephtriaxone to cover gram(+) and gram(-) but in elderly add ampicillin to cover Listeria.
