Lecture 25 - Neisseria gonorrhoeae

Question 1

discuss the global incidence and emergency of n gonorrhoeae

Answer 1

• 90mil cases but underrep bc mostly men reported
• emergency bc resistance rising
• reduction strategies didnt work = 85mil cases

Question 2

discuss the epidemiology of n gonorrhoeae in australia and the us

Answer 2

australia
- STIs in groups
- gonorrhoea increasing @ higher rate
- socially mobile groups affected = 50% cases young adults

US
- 24k women/yr infertile from undiagnosed STIs
- morbidity of gonorrhoea falls on women not men

Question 3

describe the transmission, symptoms, complications and treatment of gonorrhoeae in men

Answer 3

• urethra, 1-7 day incubation, sex/throat, 95% symptomatic
• dysuria, urethral discharge
• epididymitis, urethral stricture, prostatitis
• antibiotics + declare close contacts

Question 4

describe the transmission, symptoms, complications and treatment of gonorrhoeae in women

Answer 4

• endocervix, 20-80% symptomatic, not as acute/immediate
• dysuria, vaginal discharge, abdominal pain, vaginal bleeding, fever
• pelvic inflammatory disease (PID), sterility, ectopic pregnancy, perihepatitis/Fitz-Hugh-Curtis syndrome from scar tissue
• antibiotics but doesnt prevent PID = high morbidity for life

Question 5

list 5 other manifestations of gonorrhoea

Answer 5

1. disseminated into blood
2. dissem acute = fever, chills, malaise, bacteraemia, lesions, septic joints/arthritis
3. ophthalmia neonatorum in baby during vag delivery
4. extragenital = pharyngitis, anorectal
5. fatal gonorrhoeal endocarditis

Question 6

how are specimens taken and transported, and what is the morphology?

Answer 6

• swabs = discharge, urethra, endocervix, anal, oral, eye, blood, joint fluid
• transgrow, JEMBEC, Amies medium transport
• plate within 6hrs on thayer martin (MTM) agar
• small gray translucent raised colonies
• g-ve kidney shaped diplococci, verify women’s with penicillin disk test bc resistant

Question 7

discuss the therapy emergency of gonorrhoea in terms of the antibiotics available

Answer 7

• ceftriaxone last effective but failing
• ceft with azithromycin for chlamydia but gonorrhoea now resistant to azithro
• other antibiotics short supply/side effects

Question 8

define multi-drug resistance (MDR) and extensive drug resistane (XDR)

Answer 8

• MDR = decreased suscep/resistance to 1 recom therapy + >2 other antimicrobials
• XDR = decreased suscep/resistance to 2 recom therapy + >2 other antimicrobials

Question 9

how/where did MDR in n gonorrhoeae arise?

Answer 9

Point mutations + resistance markers from natural transformation from commensal Neisseria exposed to antibiotics in host

Question 10

describe sulphonamide resistance in n gonorrhoeae

Answer 10

• over-synthesis of para-aminobenzoic acid
• chr point mutations in dihydropteroate synthetase = prevent sulphonamide binding

Question 11

describe quinolone resistance in n gonorrhoeae

Answer 11

• chr mutations in gryA and parC for DNA rep

Question 12

describe macrolide resistance in n gonorrhoeae

Answer 12

• chr ermBCF methylase mutations for 23S rRNA = prevents antibiotic binding
• chr mtrR repressor mutation = increase MtrCDE efflux pump

Question 13

describe beta-lactam resistance in n gonorrhoeae

Answer 13

• plasmid beta lactamase = degrades penicillins
• chr penAB PBPs mutations, ponA porin, mtrR for mtrCDE efflux pump

Question 14

describe tetracycline resistance in n gonorrhoeae

Answer 14

• chr rpsJ 30S = prevent binding to ribosome
• chr penB, mtrR for efflux pump
• plasmid tetM ribosomal protection protein

Question 15

describe spectinomycin resistance in n gonorrhoeae

Answer 15

chr spc rRNA mutation

Question 16

describe aminoglycoside resistance in n gonorrhoeae

Answer 16

chr kan gene mutation

Question 17

what is treatment failure and how has it affected transmission of N gonorrhoeae?

Answer 17

• resistance enters patient population and increases logarithmically
• not compliant to antibiotic + resistant strain = spread resistance and increase treatment failure

Question 18

how does gonococcal infection affect other STIs with reference to Australian stats?

Answer 18

• increase other STI transmission esp HIV
• gonorrhoea 1.5x increase = 10% increase in HIV

Question 19

what 4 reasons why vaccines for n gonorrhoeae are difficult to design?

Answer 19

1. transforms naturally
2. recombo with DNA fragments = change sequence and antigenic variation
3. genetic drift of immunogenic targets = strain specific immunity
4. suppresses B/T cells = poor immune response

Question 20

what is another potential method of intervention for N gonorrhoeae?

Answer 20

• Early intervention = prevent transmission eg pre-exposure prophylaxis
• need to find inhibition targets essential for rep/survival/unique VFs

Question 21

describe the overall biosynthesis of lipooligosacc/endotoxin in neisseria

Answer 21

• OM’s Kdo backbone formed by sequentially adding sugars
• product transprted by LptA-F pump
• Phosphoethanolamine transferases (EptA) add phosphoethanolamine (PEA) to lipid A groups = less -ve for less attraction by cationic anitmicrobials (CAMPs)

Question 22

how is n gonorrhoeae’s infection process relevant to resisting CAMPs? how would inhibition of this pathway effect this?

Answer 22

• on epithelial surface inducing inflammatory cascades = neutrophils sent
• obligate intracellular in neutrophils bc resist CAMPs = purulent exudate
• inhibition = inhibit inflammation and allow neutrophils to kill bacteria

Question 23

what is a potential inhibitor of eptA?

Answer 23

eptA inhibitor INH-2 combo with ceftriaxone (synergistic) to restore therapy in infected macrophages