BIOL M2 L10-L11

• Bacteroidetes:

  these are a diverse group of bacteria often associated with the human gut.
• Bacteriophages are an interesting potential source of novel bacteriocidal therapies. What might complicate the use of bacteriophages in human medicine? 

  Bacteriophage host range can be very narrow. Finding the bacteriophages that are appropriate for an infection can be very time consuming. 
• Imagine that you are a physician who is treating an elderly female patient with a perforated bowel. A standard course of antibiotics was administered but the patient has now developed a hospital-acquired Clostridium difficile infection. The patient and her family are asking how this could have happened. How could you answer this?

  Hospital-associated acquisition of this infectious organism is the only route to becoming ill with Clostridium difficile.
• Antibiotic use can lead to antibiotic resistance in bacterial populations. How does this occur?

  Horizontal gene transfer between resistant bacteria and non resistant bacteria spreads resistance. 'Only those bacteria that are now resistant will be able to replicate in that environment and they will become more abundant. '

  Random mutations in populations take place and some of these can make the bacteria resistant to the antibiotic. " "
• Roughly how many kilograms does the average human microbiota population weigh?

  2 kg
• How many genes does the human genome contain?

  25,000 genes
• how many genes does the microbiome contain?

  12,500,000 (500x more than the human genome)
• All microbiomes are unique
• The prokaryotes in your microbiome :

  Liberate nutrients from otherwise inaccessible dietary substrates

  Promote differentiation of host tissues

  Stimulate the immune system

  Protect the host from invasion by pathogens
• Methanobrevibacter is an archeaeum which increases calories for the host by breaking up polysaccarides
• Probiotics are :

  live microorganisms that are supposed to confer a health benefit
• Prebiotics are :

  substrates that are intended to selectively feed microorganisms in the gut
• What causes ur microbiome to change over time?

  Diet, antibiotics, environment, illness
• Many lose lactase expression as they age, why is this?

  As we age our gut gets a different profile of microorganisms. Bifidobacterium (responsible for milk digestion) is replaced by bacteroids (carbohydrate eaters).
• What is the hygiene hypothesis?

  The hygiene hypothesis states that early childhood exposure to particular microorganisms protects against allergies by strengthening the immune system.
• Bacteriophages

  • They have a protein coat around their genetic material
  • They contain DNA or RNA
  • Some have a tail to attach to bacteria
  • They infect specific types of bacteria
• Bacteriophage lifecycle

  1. Attach to bacteria

  2. Inject their DNA

  3. Replicate inside

  4. Burst out
• Lytic cycle

  Bacteriophages replicate and burst bacteria
• Lysogenic cycle

  Bacteriophages integrate into bacteria's DNA
• Lytic Cycle

  • Attachment: Phage attaches and injects DNA
  • Replication: DNA replicates, and new phages assemble
  • Lysis: Host cell bursts, releasing new phages
  • Effect on Host: Host cell dies
• Lysogenic Cycle

  • Integration: Phage DNA integrates into host DNA
  • Replication with Host: Phage DNA replicates with host DNA
  • Induction: Under stress, phage DNA exits and enters lytic cycle
  • Effect on Host: Host cell survives unless induced, then it dies
• comparison of lytic and lysogenic life cycles

  • Effect on Host: Lytic kills host, lysogenic lets host survive until induced.
  • Timing: Lytic is immediate, lysogenic can be delayed.
  • Transmission of Genetic Material: Lytic directly transfers DNA, lysogenic integrates DNA into host, potentially transferring new genes.
• All bacteriophages have a nucleic acid genome encased in a shell of phage encoded capsid proteins, which protects the genetic material and mediates its delivery into the next host cell.
• 80% of antibiotics are used on animals due to crowded farming conditions to prevent diseases
• short term consequences of overusing antibiotics

  1. Bacteria become resistant to antibiotics, making infections harder to treat.
  2. Resistant bacteria spread easily, making infections more common.
  3. Antibiotics become less effective, so illnesses last longer and cost more to treat.
• long-term consequences of overusing antibiotics

  1. health crises : If we continue at the current rate, it's estimated that more people will die from antimicrobial resistance than cancer by 2050.
  2. As more bacteria become resistant to antibiotics, treatment options become limited, leading to longer illnesses, increased healthcare costs, and higher mortality rates.
  3. Pharmaceutical companies stop making new antibiotics because they're not profitable.
• Bacteria

  • They evolve resistant mechanisms to survive antibiotic exposure
• Agricultural Industries

  • The use of antibiotics in agriculture contributes significantly to the development of antibiotic resistant bacteria
• The Public

  • Overuse and misuse of antibiotics by the public contribute to the problem of antibiotic resistance
• Medical Professionals

  • Inappropriate prescribing and use of antibiotics by healthcare providers can accelerate the development of resistance
• Pharmaceutical Industry

  • The continuous evolution of antibiotic resistance has led some pharmaceutical companies to exit the antibiotic field due to the lack of profitability
• Describe the pros and cons of bacteriophage use in the context of specific practical application

  Pros:

  1. They target specific bacteria, sparing good ones.
  2. There are loads of different types, increasing chances of finding the right one.
  3. They break down naturally, leaving no chemical residue.

  Cons:

  1. Finding the right phage for an infection can be tough.
  2. We know about only a fraction of existing phages.
  3. Once they're done, they're destroyed.
• Changes in the diversity of the human microbiota over time

  Antibiotics can mess with the balance of bacteria in our gut, reducing diversity and causing trouble like Clostridium difficile infection (CDI)
• CDI is a serious problem, with around 29,300 deaths each year
• CDI often occurs in hospital settings, where there is an increase in C. difficile spores, and where patients are frequently exposed to antibiotics.
• Antibiotics don't even work against CDI in 15-26% of patients
• Recurring CDI infections are tough to treat
• Factors affecting how CDI plays out

  • Type of antibiotic use
  • Length of antibiotic use
  • Person's immune system
  • Hospital conditions
• what are some strategies to mitigate CDI risk

  strategies involve promoting microbiota diversity through measures such as probiotic supplementation, fecal microbiota transplantation, and judicious use of antibiotics. Additionally, infection control measures in hospitals, such as proper hand hygiene and environmental cleaning, can help reduce the spread of C. difficile spores and prevent CDI outbreaks.
• 93.8% of repeat CDI patients are cured without relapse