Mycobacterium Tuberculosis & Streptococcus Agalactiae Flashcards

1
Q

Which bacterium causes tuberculosis, and how is it transmitted?

A

Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosis, and is transmitted through air when people with TB cough, sneeze, or spit.

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2
Q

Which organ is primary affected by tuberculosis?

A

Pulmonary TB (lunge) is most common, but any organ may be affected.
TB meningitis and miliary TB is the most severe.

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3
Q

What are the general symptoms of TB?

A

Fever, weight loss, reduced appetite, weakness/fatigue, night sweats.
Lung symptoms: cough for several weeks, sputum which may be blood stained, chest pain, breathing problems.

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4
Q

How is TB treated?

A

Treatment with several active drugs at the same time to ensure cure and avoid relapse of the disease, normally for 4-6 months.
The most common antibiotics used are: isoniazid, rifampicin, pyrazinamide, and ethambutol.

Directly observed treatment, short course (DOTS):
- First two months with four drugs
- Then four months with two drugs

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5
Q

What is primary and secondary resistance?

A

Primary resistance: no previous treatment
Secondary resistance: developed during treatment

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6
Q

What is Line-Probe Assays (LPA)?

A

DNA is extracted from culture or directly from clinical speciments.
Next, PCR amplification is performed using biotinylated primers. Labeled PCR products are hybridized with specific oligonucleotide probes immobilized on a strip.
Captures labeled hybrids are detected by colored bands on the strip at the site of probe binding.

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7
Q

What is latent tuberculosis?

A

Latent TB is when a patient is infected with the Mycobacterium tuberculosis, but the infection is not active. That means that the infection can not be transmitted to another person.
The bacteria lives in the body, but does not grow. The patient has not any symptoms.
Can advance to TB disease.

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8
Q

Which methods can be used to detect TB?

A

WHO recommends the use of rapid molecular diagnostic test like Xpert MTB/RIF Ultra and Truenat assays as the initial diagnostic test.

Otherwise, microscopy, culture, PCR, or molecular susceptibility analysis can be used.

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9
Q

Why is the TB rpoB important?

A

A 81 bp sequence includes mutations covering about 95% of rifampicin-resistant mutations.

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10
Q

How is TB normally treated?

A

By antibiotics.
In certain countries, the BCG vaccine is given to babies or small children to prevent TB.

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11
Q

What conditions can increase a persons risk for TB disease?

A
  • Diabetes (high blood sugar)
  • Weakened immune system (ex from HIV or AIDS)
  • Being malnourished
  • Tobacco use
  • Harmful use of alcohol
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12
Q

What characterize multidrug-resistant TB (MDR-TB)?

A

The bacteria do not respond to isoniazid and rifampicin, the two most effective first-line TB drugs. MDR-TB is treatable and curable by using other drugs, which tend to be more expensive and toxic.

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13
Q

Why is people with HIV about 16 times more likely to fall ill with TB disease?

A

HIV and TB form a lethal combination, each speeding the others progress.

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14
Q

What characterizes primary TB, and what method is used to distinguish between primary and secondary TB?

A

Chest X-rays (CXR) is a screening tool and used as a diagnostic aid to differentiate between primary and secondary TB.
Primary disease is usually characterized by a single lesion in the middle or lower right lobe with enlargement of the draining lymph nodes.

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15
Q

What are factors to consider when identifying M. tuberculosis on medium?

A

M. tuberculosis is an obligate aerobe, grows optimally at 37°C and at a pH of 6.4-7.0. It is a slow-growing organism with a generation time of 14-15 h and the colonies appear only in about two weeks and sometimes may be delayed up to 6-8 weeks. On solid media, M. tuberculosis forms dry, rough, raised, irregular colonies with a wrinkled surface. The colonies are creamy white initially, becoming yellowish or buff colored later and tough when picked off. They are tenacious and not easily emulsified.

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16
Q

What makes NGS a better approach than Xpert MTB/RIF and Line probe assays?

A

WGS pose an advantage to ideally detect all the mutations with their functional categorization as compared to Xpert MTB/RIF and Line probe assays which are limited to identify mutations in specific locus and are unable to distinguish whether a mutation leads to a change in amino acid sequence.
WGS can also identify the resistance determining mutations in new drugs.

17
Q

How is the cell wall of Streptococci?

A

Since streptococci is a gram positive bacteria, the cell wall consists of a thick layer of peptidoglycan which retains crystal violet.

18
Q

How is streptococci classified?

A

B-hemolytic vs non B-hemolytic

19
Q

What is hemolysis?

A

Breakdown of red blood cells

20
Q

What three types of hemolysis exists?

A

Alpha-hemolysis:
- incomplete hemolysis
- agar under a bacterial colony is green colored
- hydrogen peroxide oxidizes the iron in the hemoglobin forming methemoglobin

Beta-hemolysis:
- complete hemolysis of erythrocytes
- area under and around colonies are transparent

Gamma-hemolysis:
- no hemolysis
- agat under/around colony are unchanged

21
Q

What is Lancefield grouping of Streptococci based on?

A

It is based on group-specific polysaccharides in the cell wall

22
Q

What characterizes Group B streptocuccos, like Streptococcus agalactiae?

A

In humans: asymptomatic colonization of gastrointestinal tract and female genitalia. It is an invasive pathogen which can affect both infants and adults.
All strains contains the group B carbohydrate.
Typing of GBS isolates are based on: polysaccharide capsule typing, MLST, and WGS

23
Q

Is vaccines or antibiotics preferred as treatment for Streptococcus?

A

Prophylactic antibiotics is only protective against early onset disease, and has a risk of resistance development.
Vaccines may prevent stillbirth, puerperal fever, early- and late onset disease, and there are at least two promising candidate vaccines in clinical trials today.
So, vaccines are preferred before antibiotics.

24
Q

What are some GBS virulence factors?

A

1) Adhesins: adherence to host epithelial cells and extracellular matrix is vital for colonization of gastrointestinal and vaginal mucosa.
2) Hemolytic pigment: potent cytotoxin. Antioxidant with ROS-quenching properties.
3) Superoxide dismutase: GBS resist host ROS detoxifying O2-.
4) Hyaluronidase (HylB): GBD avoid host immune detection by cleaving of hyaluronic acid. Strains expressing high levels of HylB are more virulent.
5) Capsule: immune evasion by mimicking of host antigens.

25
Q

What are the functions of host factors?

A

1) High titers of antibodies targeting the capsule protect the infant from GBS disease
2) Deficiencies may render some hosts less able to combat GBS. Eg. infants born by HUV-positive mothers have higher risk of GBS disease.
3) Host defence mechanism to clear mucosal surfaces of adherent pathogenic bacteria. Exploited by BGS to ascend into uterus.

26
Q

Where does Group B Streptococcus colonize?

A

They asymptomatically colonizes the lower genital and gastrointestinal tracts but is an invasive pathogen in other host niches.
The main host niche where GBS persists as an asymptomatic colonizer is the female rectovaginal tract.

27
Q

At the cellular level, how dies GBS regulates expression of virulence factors?

A

BGS tightly regulates the expression of virulence factors through signal transduction systems, which sense and respond to various host environments and subsequently enhance survival in host environments outside the lower genital tract.

28
Q

How does the two-component system (TCS) work?

A

TCR are comprised of a membrane-associated sensor histidine kinase and a corresponding response regulator; the latter usually has DNA-binding abilities. Upon recognizing an external signal via the N-terminal domain, the C-terminal transmitter domain of the histidine kinase phosphorylates its cognate response regulator at a conserved active site aspartate residue, thereby causing confomational changes that alter the response regulators binding affinity to target DNA.

29
Q

What is the function of adhesins in Streptococcus?

A

A major strategy that GBS employs to colonize the lower genital tract as adherence to epithelial cells via surface-associated adhesins.
A common ability conferred by these adhesins is GBS binding to components of the extracellular matrix. Some GBS adhesins execute additional functions, such as cellular invasion and immune evasion. Importantly, contact between GBS and host cells via adhesins is vital for establishing a niche in the gastrointestinal and vaginal mucosa and for invasion into other host compartments. In general, binding to surfaces improves GBSs ability to cross host barriers, which is most likely why the enhanced ability to bind host cells increase GBSs pathogenic potential.

30
Q

What is SSR1/SSR2?

A

The GBS serine-rich repeat (SSR) glycoproteins are surface-associated Fbs that bind to a single tandem repeat region of human fibrinogen via a “lock, dock, and latch” mechanism.

31
Q

What is the functions of FbsA, FbsB, and FbsC?

A

The Fbs-proteins are fibrinogen-binding proteins encoded by GBS.
FbsA and FbsC are central to GBSs ability to adhere to human epithelial cells, which likely promotes vaginal colonization. In addition, FbsC mediates biofilm formation, which could facilitate vaginal colonization by binding to other commensal microbes in the gastrointestinal and/or vaginal tract. FbsB is also thought to be important for GBS dissemination by promoting bacterial invasion of human epithelial cells.

32
Q

What is the lmb gene?

A

The lmb gene encodes the laminin binding protein of GBS (Lmb), which mediates binding to laminin, a major component of the basement membrane in tissues throughout the human body. The ability to bind laminin on the basement membrane of damaged tissued may be a key mechanism that GBS uses to disseminate in the human host.