Gram Positive Bacilli

What are Bacillus traits?

• Diverse genus, Gram positive rods, form endospores

• Gram variable (related to the age of the culture)

What kind of illness does B. cereus cause?  How is it contracted?

• B. cereus can cause rapid onset/rapid recovery type food poisoning (like S. aureus)

• Can also cause diarrheal, later onset food poisoning in immune-compromised people

• Contracted through the ingestion of STARCHY foods

Differentiate between rapid onset and long onset food poisoning.

rapid onset: symptoms appear within 30 mins-6 hours after ingesting contaminated food, symptoms are brief and quick-passing

long onset: symtoms can appear in 1-3 days or longer, symptoms last longer

What is Bt toxin?  What are GM crops?  Why are they important?

• Bt toxin is a potent pathogen specific to certain orders of insects and safe for humans to consume (through soil)

  • used as a pesticide

• GM crops are genetically modified crops and Bt toxin is a controversial agent that is used in some

  • the Bt toxin gene is introduced to corn, recombines into its DNA

What species causes the disease anthrax?

Anthrax is caused by Bacillus anthracis

Describe the characteristic symptoms and progression of the 3 types of anthrax. Which is more common? More deadly?

• Cutaneous

  • Vast majority of natural cases (more common)

  • Black ulcerative lesions

  • Usually accompanied by low-grade fever and malaise

  • 20% mortality if untreated and ~1% if treated

• Gastrointestinal

  • Nausea, vomiting from an exotoxin

  • Causes ulcerative lesions in the gut (^^ sores like above but in the GI tract)

  • 25-60% mortality, effectiveness of treatment is unknown

• Pulmonary (“wool-sorter’s disease”)

  • Extremely rare naturally

  • Initial symptoms (1-6 days): coughing, mild fever, some chest pain

  • Bacteria enter the bloodstream and multiply for 2-3 days

  • Sudden, severe septic shock

  • Mortality is ~100% untreated and ~75% if treatment started after symptoms show (more deadly)

How are symptoms primarily invasive for anthrax? (describe the process)

• reproduce until there are millions of cells/mL of blood

• bacteria weaken blood vessel walls, allowing fluid leakage

• produces severe se[tic shock

• non-inflammatory

How does inhaled B. anthracis move from the lungs to other parts of the body?

Macrophages act as Trojan horse

• carry the endospores deeper into the body before being killed by bacterium

• then the endospores are now in your body :’(

What are the 3 avenues of attack that B. anthracis have?

• produce a toxin that kills macrophages

• produce a toxin that interferes with phagocytosis

• unusual capsule: no or nearly no response by the immune system

What causes death in inhalation anthrax cases?

Inhalation of 10-20K spores can cause death

What are Clostridium traits?

• Gram positive, obligate anaerobic, spore-forming rods

• common soil bacterium

• non-pathogenic variants found in intestines

Is a C. tetani infection invasive or non-invasive?  How does it cause disease?

C. tetani is non-invasive

• causes disease by opportunistic infection of wounds (ie; puncture wounds)

  • spores germinate and grow in the wound (which is an anaerobic pocket)

  • produces several exotoxins that affects the nervous system

    • exotoxin: TETANOSPASMIN blocks the neurotransmitters that give the “relax” massage → causes rigid paralysis

What are the symptoms and outcomes of tetanus?

• muscles become rigid from constant spasms

  • starts with jaw muscles (lockjaw)

• muscle spasms can break bones

• eventually fatal due to respiratory failure

What does the tetanus vaccine give us immunity to?  Are boosters required?

• tetanus vaccine is a toxoid vaccine (inactivated toxin) against tetanospasmin

• the tetanus vaccine gives us immunity to tetanus, diphtheria, acellular pertussis

  • boosters are required

What's the most important step in treating tetanus? Will recovery be rapid or slow?  Why?

• Administration of antitoxin

  • Serum from immune people; antibodies against tetanospasmin

• Administration of tetanus vaccine

• Original wound is debrided (cutting away dead tissue) and disinfected

• Rest is also important

  • recovery is slow because new nerves must grow to replace the damaged ones

What gives gas gangrene its name?  Is the infection invasive?

gas gangrene is named for the gasses produced by Clostridium perfringens

• the infection is invasive

  • exoenzymes eat away surrounding tissues and produces large amounts of gasses that push oxygen out of surrounding tissues

How is an anaerobic organism able to grow and spread through normally oxygenated tissues?

• They are able to grow and spread through anaerobic environments 

  • They live in soil and intestines

• They have to find an acceptable environment

• They can be found on skin but in low numbers

What is debridement?  Why is it extra important for Clostridium infections?

Debridement is the removal of dead, damaged, or infected tissue to improve healing

• It is important for Clostridium infections because they are opportunistic pathogens that will find a suitable place to infect

• Other treatment for gangrene:

  • wound is debrided, antibiotics, antitoxin, hyperbaric chamber (drives oxygen into your body), amputation/death (rare)

Compare adult botulism vs infant botulism

• what causes the disease?

• is it an infection?

ADULTS

• Eat C. botulinum spores and it produces exotoxin but our strong gut microbes kill them

  • The disease is caused by food and infects the food not us

INFANTS

• Eat C. botulinum can germinate and colonize, and produce the exotoxin within the infant

  • Infants are vulnerable to infection due to underdeveloped flora

Describe the symptoms of botulism (aka “sausage disease”)

• 12-36 hours after ingestion

• Double-vision, fatigue, difficulty swallowing

• Progressive flaccid paralysis: contraction signals are prevented from reaching muscles, so your muscles relax all the time/cannot move at all)

• Respiratory failure, cardiac failure, death

What's the most important part of the treatment of botulism?

The most important part of treatment is that it must be rapid

• USE ANTITOXINS for adults and infants (serum from immune individuals)

How do we prevent botulism typically?

• Handle food properly!!!

• Heat canned foods long enough to kill spores

• Clostridium does not like acidic foods, high sugar content, or addition of nitrite preservatives prevent spore germination

• The toxin is heat-sensitive (boiling)

What about botulism toxins that allow Botox injections to last for months?

• Botox is diluted Clostridium botulinum

• They last for months because the nerve damage is semi-permanent and it must regenerate

What is antibiotic-associated diarrhea?  Why does it occur? 

Clostridium difficile (C-dif) is a major cause of antibiotic-associated diarrhea

• It is diarrhea that is caused by extended antibiotic usage, gastric acid-blockers, chemotherapy → things that reduce normal intestinal flora

  • non-invasive colonization of the guy, produces exotoxins

What are symptoms of Clostridium difficile? How is it diagnosed?

• Symptoms include diarrhea, abdominal pain, cramping, foul smelling stool; may lead to bowel perforation

• It is diagnosed by symptoms above and can be confirmed with PCR or serological tests of stool samples (must identify colonization vs infection)

What is pseudomembranous colitis? Define a pseudomembrane.

• Underlying condition of C-dif

• Pseudomembranous colitis is the inflammation of the intestine and formation of pseudomembrane in the intestine

• A pseudomembrane is something that resembles a membrane but it’s not

  • it’s a biofilm generated by bacterium and dead immune cells that are trying to kill the bacterium; covers lining of intestines

How is Clostridioides difficile treated? What is FMT?

• cease normal antibiotics treatment, switch to an antibiotic that is effective against C. difficile

• FMT (fecal microbiota transplantation) - pills of fecal matter (containing good gut flora) of someone healthy are transported into a person with intestinal disease

what are Corynebacterium traits?

• Gram positive, facultative anaerobic, pleomorphic (many form, irregular shape) rods

Describe diphtheria.  Is it invasive?  What causes the symptoms?

• It is pharyngitis (infection of the throat) and some of the symptoms are:

  • Fever, fatigue

  • Sore throat

  • Difficulty swallowing

  • Neck swelling

• Diphtheria pseudomembrane in the throat

  • grey, touch accumulation of dead cells

  • can cause choking

• Diptheria is non-invasive

• Symptoms are caused by the diphtheria toxin (on a bacteriophage)

  • kills cells by inhibiting protein synthesis

    • Blocks eukaryotic ribosomes

  • It is also roughly as toxic as tetanospasmin

    • Not as much produced, acts locally

What is the DTap or TDap vaccine targeted against?  What are we immune to when vaccinated?

• the vaccine is targeted against the diptheria toxin

  • It is a toxoid vaccine (inactivated toxin)

• We become immune to the toxin

What's the most important part of treatment for diptheria?

• The most important part of treatment is use antibiotics to reduce the bacterial population

• + the antitoxin from immune individuals to inactivate the toxin

Would the diptheria most likely come back if vaccinations stopped?  What evidence is there of this?

• It would likely come back if vaccinations stop because that is what keeps it at bay

• There is evidence of this with the failure of the Soviet Union to vaccinate

what are Listeria traits?

• Gram positive rods, facultative anaerobes, no spores

• psychrotrophs - able to grow at 4°C

• halophilic - able to grow in high salt

• common in the environment

Will refrigeration stop Listeria from growing?

No

How does the way Listeria move from cell to cell help avoid the immune system?

• Inside cells they use something called “actin polymerization” (via flagellar motility)

What are the symptoms of Listeria for healthy individuals?

• Healthy men and non-pregnant women

  • Mild food poisoning

How is Listeria more serious for pregnant women?

• Pregnant women

  • Usually presents as mild flu-like symptoms (fever, fatigue, nausea)

  • High chance of misscarriage or stillbirth

• Research in pregnant guinea pigs shows that Listeria migrates specifically to the placenta

How is Listeria more serious for immune compromised people?

• Immunocompromised patients

  • The disease persists and can spread to the CNS

  • ~25% mortality

What can be done to avoid listeriosis? What does treatment include?

• Cook food thoroughly

• Avoid deli meats, unpasteurized (soft) cheese

• Avoid food that has been refrigerated for a long time

• Treatment includes using aggressive antibiotics (ampicillin)

describe the typical shape and environmental location of Streptomyces series

gram-positive rods, obligate aerobes and grow in long mycelium-like filaments

What makes Streptomyces particularly interesting in medicine?

They produce a massive variety of bioactive agents

• 2/3 of our antibiotics

• anti fungals

• anti-cancer agents

• immunosuppressant