Medical Microbiology Class 11
Chlamydia:
they have a small genome, about 1000bp. Obligate intracelluar pathogen, two stage developmental pathogen. The first stage is outside of the cell where it cannot reporduce, adn the second is the reproductive stage where it can be reproduced. However the first is still infectious
C. trachomatis is an obligate intraceuluar pathogen and can cause numerous disease in both mena dn women. Most common STD in the western world.
Often insidious asymptomatic
Also important neonatal.
It is a STD that leads to people when it is symtpomatic, resulting in symptoms such as urethritis in men and cervicitis in women, which can lead to severe complications if left untreated. Can lead to a reduciton of fertility, cervical infection, etc in women.
Why is the genome small? becuase it gets what it needs frrom the host and relies on the host's cellular machinery for replication and survival, minimizing the need for a larger genome. No deteectable genes for AA biosynthesis, flavoproteins or cytochriomes. In fact, they thought it could not syntheisize ATP—however discovered later that it can make its own energy
Genome seq revealed that there are genes for several catabolic patheays that woul dallow for substrate level synthessi.
Elementary Body: EB—is the external cell form of this pathogen, wher it is much smaller, it is metabolically inactive, however this form does allow it to survive in external environemnt and infectious in this form.
Reticulate Body (RB): The active form of the bacteria, where it grows to 1 micron, intracellular replicative, and after replicating a lot, returns back to the EB form to lyse the cell.
There is no peptidoglycan; however the EB is resistant to lysis through the membrane proteins with many di-sulfide cross-links. This means that we cannot use antibiotics that target the cell wall.
The EB has the machinery to ID the cell, ID epitopes and infect the relevant cells (epithelial reproductive cells). Once it attaches to the cell, it injects proteins into the cell, which alert lectins to endocytose the microbe and let it in.
Once the bacteria gets into the cell, it begins a process where the bacteria transitions to the EB and RB and neutralizes the preventative measures f the cell against it. For example, formation of the endolysosome would kill it. Therefore, it fuses with the endosome and takes control of it, allowing it to evade degradation and replicate within a protected environment. Once it gets to a high concentration of RBs, the RBs develop into EBs and are released from the cell.
Important to understand: the target that we first need to target is the EB. Very not immunogenic; however easy to make antibodies against the RB (however it isn’t exposed to the outside of the cell, therefore this is useless.)
Treatment is largely focuses on antibiotics that aren’t beta-lactams or cell-wall inhibition or gentamycin that get into the cell.
To diagnose, it used to be based on lab culture, but today it is PCR.
Yersinia pestis Gram negative, anaoerbic facultative, and pestis leads to the plague.
Y. enterocolitica and Y pseudotuberculosis—causative agents of gastroenteritis.
Yersinia pestis is transmitted through flea bites or direct contact with infected animals, leading to bubonic or septicemic plague.
Y. enterocolitica can be found in contaminated food, particularly pork, and can cause severe abdominal pain and diarrhea.
Y. pseudotuberculosis primarily affects animals but can also infect humans, leading to similar gastrointestinal symptoms.
Y pestis and pseudotuberculosis are 99% identical while Y enterocolitica is more distant. However the disease caused by Y pests and its lifecycle is different from the other two wishi care similar.
Y pseudotuberccolitis: got mutations that allowed it to have a new vector—leading ot Y pestis to be transmitted by flea and pentrate the BBB, unlike its cousin that could really only get in through the GI tract.
How do we know that pestis caused the Black Death? Because of PCR analysis on teeth of peopel who purportedly died from them. It has been used a biowarfare weapon in history.
Pestis when it appears, the deadline to treat it is very small (24 hours aftr appearance of symptoms). Causes bubonic plague, then pneumonic plague which are both highly infectious and can lead to severe mortality if not treated promptly. This highlights the importance of early detection and rapid intervention in managing outbreaks.
Yersina is important becuase itis important for studying host-microbe interaction, it is NOT oportunistic;
The way it infects is the flea-mammal cycle. The bacteria are transmitted through flea bites, which then leads to a rapid multiplication in the host's bloodstream, causing severe symptoms if not treated promptly.
The flea is the main vector. Y pestis replciate and clump to form a plug that prevents the flea from feeding. This results in the flea regurgitating the bacteria back into the host during feeding, further facilitating the spread of the infection.
Typically, the bubonic plague gets into the lymphatic system. If untreated, it progesses to the lungs where it becomes airborne.
Bubonic plague is characterized by swollen and painful lymph nodes, known as buboes, which can lead to severe fever and chills.
Food borne Y enterocolitica and Y pseudotuberculosis: gets into blood stram adn leads to lung infection, but not to the level of the pestis. Pestis cannot get into the bloodstream through the GI tract, unlikes its relatives.
There are a ton of plasmid that bring them virulence factors.
They have a Type III secretinion system that allows them to inject virulence proteins directly into host cells, facilitating infection and evasion of the immune response. concerted antiphagocytic activity of yop effectors.
They also have an iron gathering system that is advanced. They heve receptors for Heme B.
Diagnositic:
direct microscopic examination, culture of the bacterium, serological tests, etc.
Treatment and prevention: vaccine no longer available; however, antibiotic therapy is effective if administered early. Additionally, maintaining proper hygiene and sanitation can help prevent the spread of infections.
Clostridium: gram + bacteria, obligate anaerobes, and makes ENDOSPORES. Things to rememebr!!
The endospore is the EB,
Clostridium botulinum: often fatal, produces a potent neurotoxin that can cause paralysis and respiratory failure if ingested, making it crucial to ensure proper food preservation and handling. Most cases are food brone, contaminated food where the bacteria secreted the toxin.
Epidemiology: needs an aneorobic environemtn, and find it in food preservatives. Common source of canned food poisoning in the early 20th century.
Really the issue with this bacteria is not the bacteria itself; its the toxin. Therefore, the reatment is often the antidote for the toxin, not antibioitics.
Pathogenesis: tthe spores can germinate if the pH is above 4.5, anaeronbic, and tempeorature above 39 C. One of the reasons we do not give babies honey is because it might have the spores.
The structure of the baby 's digestive system is still immature, which makes them particularly susceptible to the spores and the toxins they produce. As soon as the infant can eat solid food, the digestive juices become too acidic for the bacterium to grow.
Botulism is an AB toxin: it inhibits the release of acetylcholine at the neuromuscular junction, leading to muscle paralysis and respiratory failure.
Botox is a purified form and small dose of the botulinum toxin used therapeutically for various medical conditions and cosmetically to reduce wrinkles by temporarily paralyzing muscles.
Preventiona dn Treatment: proper sterilization and sealing of food at the time of canning. Toxin is heat labile and heating food to 100C before eating for 15 min is suffiient. The treatment is antitoxin.
Clostridium tetani: rod shaped anaerobic bacterium that causes tetanus. Very common to be found as spores in soil, dust, and animal feces, Clostridium tetani spores can survive in harsh conditions for long periods and can enter the body through wounds or cuts. In addition to proper wound care, vaccination against tetanus is crucial, as it helps to build immunity and prevent the disease from occurring. C tetani produces a potent biological toxin, tetanospasmin, and is the causative agent of tetanus, and leads to painnful muscular spasms.
Symptoms:
vaccination is against the toxin, treatment is the antidote for the toxin.
Epidemiology: puncture wounds where the spore gets in, surgery, burn wounds, neonatal tetanus (unsterile cut of the umbilical cord).
Clostridium difficile: a bacterium that can cause severe diarrhea and colitis, often associated with antibiotic use, and is transmitted through fecal-oral contamination. Usually through nocomial infection with people who have undergone severe antibiotic treatment. This leads to an issue with the microflora of the gut, and the overgrowth of C. difficile, resulting in an imbalance that can cause inflammation and damage to the intestinal lining.
Leads to PMC (pseudomembranous colitis), a serious condition characterized by inflammation of the colon, which may present with symptoms such as abdominal pain, fever, and significant diarrhea. Many elderly people get it.
With the introduction of broad-spectrum antibiotics and chemotherapeutic agents antineoplastic drugs , there is an increased risk of disrupting normal gut flora, exacerbating the problem of C. difficile overgrowth, and consequently heightening the incidence of PMC among vulnerable populations.
Pathogenesis: enterotoxin TcdA and cytotoxin TcdB and the binary toxin CDT. In non-toxigenic strains, the strand that codes for this is filled with nonsense short 115bp sequence.
The toxins are produced during the late log and stationary phases.
The toxins work through a hierarchy. TcdA works on the apical side of the intestine—opens tight junctions between cells and TcdB goes through and gets into the blood stream.
Diagnosis and treatment: In the past, this was very complex due to the overlapping symptoms with other gastrointestinal infections, but advancements in diagnostic techniques, such as PCR and enzyme immunoassays, have improved accuracy. Treatment typically involves the use of antibiotics like metronidazole or vancomycin, along with supportive care to manage dehydration and electrolyte imbalances. Probiotics are also being explored (donor feces) as a potential therapeutic option, aiming to restore the balance of gut microbiota and reduce recurrence rates of infection.