STIs Flashcards

Question

what is PilE?

Answer 1

- PilE is the main gene that encodes pilin subunit - In the pilin subunit, the N-terminus is highly conserved to build the pilin structure/fibre - The outside of the fibre is variable region which can be detected by T cells/antibodies

Answer 2

N. gonorroheae can swap out the variable region of the gene in a recombinase-dependent manner during growth - Partial sequence homology between the silent pilS loci and the expressed pilE gene allows RecA-mediated recombination to occur, giving rise to a novel pilE variant protein, by “gene conversion” - Constantly mixing and matching the silent genes, then incorporating into variable region - The pilin will still be functional, but less recognizable by host immune system

Answer 3

- Population of N. gonorroheae cells inoculated from a single colony, genetically identical/clonal, and then you sequence the variable region of the pilin, they will all have different sequences - This means host immune cells cannot recognise all the cells in the population due to antigenic variation

Answer 4

- Asymptomatic carriers are major reservoirs of infection in the human population (up to 50% of females, and 10% of males) - Tracing and treatment of sexual contacts of infected symptomatic individuals is important in preventing spread

Answer 5

- 1940s -1970s: Penicillin, but resistance became a major problem - 1980s: Fluoroquinolones, e.g. ciprofloxacin (DNA gyrase inhibitor) - resistance now a major issue so they cannot be used, DNA gyrase can undergo point mutations so quinolones are redundant - 2000s – present: Cephalosporins, e.g. ceftriaxone and cefixime - resistance is becoming quite common

Answer 6

multi-drug resistant gonorrohea – there is a real possibility this may become an untreatable disease

Answer 7

Flagellum is within the periplasmic space, and bacterium is spiral in shape - T. pallidum is a spirochaete causing syphilis - Borrelia can cause Lyme disease – tick borne zoonosis causing infectious arthritis - Leptospira cause leptospirosis (Weil’s disease), transmitted through rat urine or faeces

Answer 8

- A complex disease, first described in Europe in the 1400s. - Its symptoms can be varied and easily confused with other diseases, making traditional diagnosis difficult (“The Great Imitator”) - Caused by the spirochaete Treponema pallidum, discovered in 1905 - Infection is CHRONIC and in untreated cases may last decades, with maybe 30-50% mortality. - The disease progresses in different stages

Answer 9

- spirochete bacteria - very fragile - slow growing - poor survival outside the host

Answer 10

Infection requires intimate sexual contact, and is aided by minute tissue abrasions that occur during sex

Answer 11

primary secondary latent tertiary

Answer 12

- Initial infection presents as chancre sores on penis/vagina/anus - Short-lived - Some patients who notice the sores won’t seek diagnosis/treatment - Primary infection will either lead to secondary/systemic infection or latent infection

Answer 13

- systemic infection including rash, fever, neurological symptoms - neuro-syphilis can be fatal - these harsher symptoms occur < 1 year - after this infection, the illness resorts to latent infection

Answer 14

there are no symptoms expressed - the bacteria resides in the body and can reactivate back to systemic/tertiary infection 5-50 years later - 30% with latent infection will progress to the severe syphilis infection

Answer 15

5-50 years later, infection progresses to nasty systemic infection of bones, cardiac tissue, nerve disease - Affects brain – patients are neurologically disturbed - Patients develop Gumma: a nodule or tumour-like growth in organs - At this point 50% patients die - 30% with latent infection will progress to the severe syphilis infection

Answer 16

* as there are so many wide-ranging symptoms

Answer 17

1. lack of endotoxins and exotoxins 2. invasion of immune-privileged tissues 3. ability to maintain infection with few organisms 4. lack of surface antigens 5. low iron requirements - can obtain sequestered iron

Answer 18

Lack of endo- and exotoxins: - T. pallidum lacks LPS, the endotoxin found in the outer membranes of many Gram-negative bacteria, so doesn’t have MAMPs that are instantly recognised by the immune system - The attachment of T. pallidum to cells does not harm the cells - This indicates that cytolytic enzymes or other cytotoxins most probably do not play a role in syphilis pathogenesis.

Answer 19

Invasion of "immune-privileged" tissues: - T. pallidum penetrates a broad variety of tissues, including so-called "immune privileged": the central nervous system, eye, and placenta, where there is less surveillance by the host's innate immune system.

Answer 20

Ability to maintain infection with few organisms: - T. pallidum may also exploit its slow growth to survive in tissues, even those that are not immune privileged. - By maintaining infection with very few organisms in anatomical sites distant from one another, T. pallidum may prevent its clearance by failing to trigger the host's immune response, which was may require a "critical antigenic mass".

Answer 21

Lack of surface antigens: - One of most prominent features of T. pallidum is that it has only rare integral proteins in its outer membrane, approximately 1% of the number found in the outer membrane of E. coli. - However, these rare proteins are likely to be very important in interactions with the host; for this reason, their identity has been the subject of intense research.

Answer 22

Low iron requirements, ability to obtain sequestered iron: - T. pallidum may be able to acquire iron from host proteins. - It may also overcome the iron sequestration problem by using enzymes that need metals other than iron as their cofactors. - In addition it lacks an electron transport chain, which is made up of enzymes that use iron as a cofactor, which decreases its overall demand for iron

Answer 23

In 1910 Paul Ehrlich developed salvarsan – an organic arsenic-containing drug which was partially effective but quite toxic

Answer 24

0 T. pallidum is very sensitive to penicillin, which is still the best treatment, as little resistance has developed. - Its introduction in the 1940s led to a massive reduction in the numbers of cases and the disease became rare. - However, because the bacterium is so slow growing it is essential that a high level of penicillin is maintained in the body for several weeks; it must be injected either daily IV or 2x injections of a slow release formulation in the buttocks over a 1 month period (painful!) - Not everyone follows through with the treatment

Answer 25

In the 1970s numbers of cases started to rise again; it is now a significant STI. - A particular problem is co-infection of syphilis and HIV – infection with syphilis makes it several times more likely that HIV infection occurs

Answer 26

Chlamydia are small gram-negative wall-less bacteria which are obligate intracellular parasites: - Cannot survive outside of mammalian host cell – cant be cultured on agar in lab - Tiny genome – genome reduction means it is dependent on host for common cell processes - like a virus

Answer 27

They have a complex life-cycle based on two functionally distinct cell forms: - “Elementary body” (EB) – survives outside of host cells and initiates infection - “Reticulate body” (RB) – Differentiates from the EB and is responsible for intracellular growth

Answer 28

Chlamydia trachomatis causes STIs, but only certain serovars: - A, B, C - cause Trachoma – a serious eye infection - D,K – cause Urethritis (men) and Cervicitis (women) - STI - L1-L3 – cause Lymphogranuloma venereum (LGV) – STI

Answer 29

- Thin, watery urethral discharge - Sometimes pain on urination - Can be asymptomatic

Answer 30

- Infection of the cervix - Urethritis - Infertility and ectopic pregnancy - Very often asymptomatic

Answer 31

Screening programmes are important because of the often asymptomatic nature of the infections

Answer 32

- Chlamydia are insensitive to beta-lactam, cephalosporin and vancomycin antibiotics as they have no peptidoglycan cell wall. - Have to use alternatives like Tetracycline/doxycycline or Azithromycin, which have some side-effects

STIs Flashcards

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