ICS Microbiology Flashcards
Define Pathogen
Organism(s) that causes or have the potential to cause disease
Define Commensal Organism
Colonises the host but causes no disease in normal circumstances
Define Opportunist Pathogen
Microbe that only causes disease if host defences are compromised
Define Virulence/Pathogenicity
The degree to which a given organism is pathogenic
Define asymptomatic carriage
When a pathogen is carried harmlessly at a tissue site where it causes no disease
Describe the morphology of bacteria
Simple organisms. Coccus if round and bacillus if rod-shaped
What is a pair of cocci called?
Diplococcus
Results of a Gram stain
Purple = Positive Pink = Negative
Difference between gram positive and gram negative bacteria.
Gram positive have very thick peptidoglycan layer, this is very thin in gram negative bacteria. Gram negative bacteria have an extra outer membrane.
Describe exotoxins
Secreted proteins, produced mostly by gram +ve bacteria.
Specific actions with strong antigenicity.
Can be converted to toxoid.
Easily altered by heat.
Describe endotoxins
Component of the outer membrane of bacteria.
Lipopolysaccharide (LPS in gram -ve bacteria)
Non-specific action with weak antigenicity.
Cannot easily be converted to toxoid
Stable in different heats
What does the catalase test do?
Distinguishes staphylococci and streptococci (streptococci are positive)
Why do gram positive bacteria stain purple?
They have a thick layer of peptidoglycan which retains the colour of the crystal violet stain.
How are gram positive bacteria managed?
Antimicrobials and vaccination
What is the structure of staphylococci?
Clusters of cocci
What does the coagulase test differentiate?
Differentiates staph. aureus (positive) from the other staphylococci
What diseases does Staphylococci aureus cause?
Pyogenic infections (impetigo, wound infections, septicaemia, endocarditis)
Toxin-mediated problem (toxic shock syndrome, food poisoning, scalded skin syndrome)
Example of coagulase negative staphylococci
S. epidermidis
What is the structure of streptococci?
Chains of cocci
Different types of haemolysis of blood agar
Alpha - greening i.e. S. intermedius
Beta - complete lysis i.e. S. pyogenes
Gamma - no lysis i.e. some S. mutans
What diseases are caused by S. pyogenes?
- Wound infections
- Tonsillitis
- Impetigo
- Scarlet fever
- Otitis media
Describe S. pneumoniae pathogenicity
- Alpha haemolysis
- Normal commensal in oro-pharynx
- Causes pneumonia, meningitis, sinusitis or otitis media
Describe viridans group streptococci pathogenicity
- Alpha haemolysis
- Some cause dental caries and abscesses
- Important in infective endocarditis
- Cause deep organ abscesses
- Examples include S. intermedius, S. anginosus etc.
What is Lancefield typing?
A method of grouping catalyse negative and coagulase negative bacteria based on bacterial carbohydrate cell-surface antigens
Examples of gram +ve bacilli
- Listeria monocytogenes
- Bacillus anthracis
- Corynebacterium diphtheriae
- Clostridia (tetani, botulism, difficile)
Describe the structure of gram -ve bacteria
Thin layer of peptidoglycan
Have a second outer double membrane.
Formed one side by phospholipids and other side by LPS (endotoxins)
Main groups of gram negative bacteria
- Proteobacteria
- Bacteroidetes
- Chlamydiae
- Spirochaetes
Main family of proteobacteria (of clinical importance)
Enterobacteria
Structure of enterobacteria
Rods, most are motile
Examples of enterobacteria
Shigella flexneri, Escherichia coli (E. coli), Salmonella enterica
What are serovars?
Distinct variations in antigenic structure between strains of the same species.
What are pathovars?
Strains or sets of strains with similar pathogenicity.
Why are some strains of E. coli commensal and some pathogenic?
There is a common core genome and pathogenicity genes can be acquired.
Examples of Shigella bacteria
S. dysenteriae, S. flexneri, S. boydii, S. sonnei.
What is shigellosis?
Pathology like that of entero-invasive E. coli but with Shiga toxin
Types of salmonella bacteria
S. enterica
S. bongori
The 3 forms of salmonellosis (caused by S. enterica)
Gastroenteritis (serovar Enteritidis and Typhimurium)
Enteric fever (serovar Typhi)
Bacteraemia
Describe Bacteroidetes
Non-motile rods
Strict anaerobes
Live as part of commensal flora of small intestine
Involved with opportunistic infections.
Which member of the Bacteroidetes is the most frequent cause of anaerobic infections?
B. fragilis
Groups of Chlamydiae
Chlamydia and Chlamydophila
Describe Chlamydiae
Very small, non-motile
Obligate intracellular parasites.
Many groups live asymptomatically.
Two types of bodies in the Chlamydiae
Elementary bodies
- round
- infectious
- enter cell through endocytosis
- prevent phagosome-lysosome fusion
Reticulate bodies
- Pleiomorphic
- Replicative
- Non-infectious
- Acquire nutrients from host cells
3 biovars of Chlamydia trachomatis
Trachoma biovar
Genital tract biovar
(LGV) biovar
Describe spirochaetes
Long, spiral shapes
Most non-pathogenic
Characterised by endoflagellum
Examples of spirochaetes
Borrelia burgdorferi
Leptospira interrogans
Treponema pallidum
Describe fungi?
- Eukaryotic
- Chitin cell wall
- Heterotrophic
- Move by growth or spores
- Infections are opportunistic
Yeasts vs Moulds
Yeasts are small single celled organisms that divide by budding
Moulds form multicellular hyphae and spores
(some fungi are both - dimorphic)
Forms that fungal infections take
Skin infections
Wound infections
Mucosal infection
Invasive infections (life threatening)
What is the aim of antimicrobial drug therapy?
To achieve inhibitory levels of agent at the site of infection without damaging the cells too much
Microbiology of mycobacteria
Aerobic, non-spore forming, non-motile bacillus.
Cell wall contains high molecular weight lipids
SLOW reproduction
SLOW response to treatment
SLOW growing
What stain is used to identify organisms with wax-like thick cell walls?
Ziehl-Neelsen stain
How does the host aim to kill mycobacteria?
Microbicidal molecules and acidification acids digestion resulting in generation of antigens for presentation to T-cells
Characteristics of viruses
- No membranes or cell organelles
- Consist of outer protein coat and strand of nucleic acid
- Come in variety of shapes
- Cannot carry out metabolic reactions on their own
How do viruses replicate?
- Attachment: viral and cell receptors e.g. HIV
- Cell entry: only central viral core carrying the nucleic acid and some associated proteins enter host cells
- Interaction with host cells: use cell materials for their replication
- Replication: may localise in nucleus, cytoplasm or both
- Assembly: occurs in nucleus, in cytoplasm or at cell membrane
- Release: bursting open of cell, or by leaking from the cell over a period of time
How do viruses cause disease?
- Damage by direct destruction of host cells e.g. HIV
- Damage by modification of host cell structure or function e.g. rotaviruses
- Damage involving over-reactivity of host as a response to infection e.g. hepatitis B
- Damage through cell proliferation and cell immortalization e.g. HPVs
- Evasion of both extracellular and intracellular host defences
Describe how Gram staining works.
- Adding crystal violet dye to bacteria on a microscope slide (after bacteria is fixed by heating over a flame)
- Washed off after a few seconds
- Iodine added and then washed off after seconds
- Decolourisation (with Gram’s alcohol)
- Counterstain (fuchsin/safranin)
Appearance of colonies in blood agar of staphylococci
S. aureus is gold
All the rest are white
How to differentiate S. pneumoniae from other streptococci?
Optochin test (S/ pneumoniae is sensitive)
Describe the oxidase test
Tests for the presence of cytochrome oxidase
Disk turns blue if positive
What are the 5 major classes of protozoa?
Flagellates Amoebae Sporozoans Ciliates Microsporidia
Describe Protozoa
Single-celled eukaryotic organisms. Engulf food via phagocytosis and have important parasitic and symbiotic relationships.
How do amoebae move?
By means of flowing cytoplasm and production of pseudopodia.
Name a pathogenic amoeba
Entamoeba histolytica
Describe the epidemiology of Entamoeba histolytica
Causes a severe dysenteric illness (amoebiasis)
More common in areas with poor water supply and contracted through faecal-oral contamination.
Combated through public health measures such as sanitation of water.
Name 4 illnesses caused by flagellates.
Trypanosomiasis
Leishmaniasis
Giardiasis
Trichomonas Vaginalis
more info on each in notes
Describe Sporozoans
Non-motile protozoa.
All species are parasitic and most are intracellular
Three diseases caused by Sporozoans
Malaria
Cryptosporidiosis
Toxoplasmosis (toxoplasma gondii)
5 species of Plasmodia sporozoan that cause human disease.
P. Falciparum P. Malariae P. Ovale P. Vivax P. Knowlesi
Vector of Malaria
Female Anopheles Mosquito
3 stages of Malaria lifecycle
Human Liver Stage
Human Blood Stage
Mosquito Stage
(diagram in protozoa notes)
Clinical features of malaria
Fever Chills and sweats Headache Myalgia Fatigue Nausea and Vomiting Diarrhoea
Which species causes severe malaria?
P. falciparum
Complications of malaria
- Cerebral malaria
- ARDS
- Renal failure
- Bleeding
- Shock
Treatment of complicated malaria
IV Artesunate
Treatment of uncomplicated malaria
Lots of options e.g. primaquine
Define infectivity
The ability to become established in the host, can involve adherence and immune escape
Define invasiveness
The capacity to penetrate mucosal surfaces to reach normally sterile sites
What is antigenic drift?
Spontaneous mutations that occur gradually giving minor changes in haemagglutinin and neuraminidase
What is antigenic shift?
Sudden emergence of a new subtype different to that of the preceding virus
What is an antibiotic?
An agent produced by microorganisms that kill or inhibit the growth of other microorganisms in high-dilution.
What does ‘antimicrobials’ include?
Antifungal Antibacterial Anthelminthic Antiprotozoal Antiviral
Main groups of Beta Lactams
Penicillin
Cephalosporins
Carbapenems
Monobactams
How do Beta Lactams destroy bacteria?
Inhibit cell wall synthesis
Which bacteria do Beta Lactams act on better
Gram positive bacteria
but still acts on some gram negative
How does Rifampicin work?
Works against RNA polymerase and inhibits RNA synthesis
What ‘accidental’ damages do antibiotics cause?
Directly Toxins Indirect - Inflammation - Immune pathology Diarrhoea
What is the action of bacteriostatic antibodies?
Prevents growth of bacteria
Kills >90% in 18-24 hours
Inhibits protein synthesis, DNA replication or mitosis
What is the action of bactericidal antibiotics?
Agent directly kills the bacteria (usually by inhibiting cell wall synthesis)
Kills >99.9% in 18-24 hours
What are bactericidal antibiotics useful in treating?
Poor penetration (endocarditis)
Difficult to treat
Need to eradicate quickly (meningitis)
What dose MIC stand for?
Minimum inhibitory concentration
Examples of antibiotics who employ concentration-dependent killing.
Aminoglycosides
Quinolones
Examples of antibiotics who employ time-dependent killing.
Beta lactams
Clindamycin
Macrolides
Oxazolidinones
4 Reasons for antibiotics not working
Changes to binding site of antibiotic target
Destruction of antibiotic
Prevention of antibiotic access
Removal of antibiotic from bacteria
How can bacteria develop resistance?
Natural innate
Spontaneous gene mutation
Horizontal gene transfer
Factors important to consider when deciding if an antibiotic is safe to prescribe.
- Intolerance, allergy and anaphylaxis
- Side effects
- Age
- Renal and Liver functions
- Pregnancy and breast feeding
- Drug interactions
- Risk of C. diff
Examples of glycopeptides and what they do.
Vancomycin and Teicoplanin. (IV) Damage cell wall of gram positive bacteria.
Used when bacteria resistant to beta-lactams
Example of Macrolides, what they do and mode of use
Clarithromycin and erythromycin
Inhibit protein synthesis
Oral (and IV if needed)
When are macrolides used?
Gram positives and atypical pneumonia pathogen.
Use in penicillin allergy or severe pneumonia
Example of Lincosamides, what they do and mode of use
Clindamycin
Inhibits protein synthesis
Oral (and IV)
When are lincosamides used?
Gram positives, used in cellulitis or necrosing fasciitis
Example of Tetracyclines, what they do and mode of use
Doxycycline
Inhibits protein synthesis
Oral
When are tetracyclines used?
Mainly gram positive, used in pneumonia or cellulitis.
Example of Aminoglycosides, what they do and mode of use
Gentamicin
Inhibit protein synthesis
IV only
When are aminoglycosides used?
Gram negatives and staphs
Use in UTIs or infective endocarditis
Example of Quinolones and what they do
Ciprofloxacin
Inhibits DNA synthesis
When are Quinolones used?
Gram negative (and positive sometimes) Use in penicillin allergy, UTIs and intra-abdominal infections. Risk of C. diff
Other antibiotics used for UTIs
Trimethoprim
Nitrofurantoin (first line for lower UTIs)
What does U=U mean in HIV?
UNDETECTABLE = UNTRANSMITTABLE
What are the two things we look for in blood tests for HIV?
- Low CD4 count (normal is 500 upwards)
- High HIV viral load
First stage of HIV course
Acute primary infection. 2-4 weeks after exposure
Transient immunosuppression and fall in CD4 count (followed by gradual rise)
Acute rise in viral load then fall to ‘set point’
What can happen in the primary HIV infection?
Abrupt onset of non-specific symptoms (can be mild or severe)
What should be done in a patient with a fever, rash and non-specific symptoms?
Ask about sexual history
Consider HIV seroconversion
What is the commonest opportunistic infection in HIV patients?
PCP
Pneumocystic pneumonia
Second phase of HIV course
Asymptomatic phase (clinical latency) Progressive loss of CD4 cells and rise in viral load.
When should we think about doing a HIV test?
Common problem in unexpected patient
No clear underlying cause to common problem
Recurring infections
Third Stage of HIV course
Early symptomatic HIV
Fourth stage of HIV course
AIDS
What is AIDS?
Acquired immune deficiency syndrome
Typical time from HIV infection to AIDS
5-10 years
Factors causing more rapid progression from HIV to AIDS
Elderly and Children
High ‘set point’ viral load
Is HIV clinically manageable using HAART?
YES!
With proper treatment even late-stage HIV has a good prognosis
What are the 6 steps of HIV virus’s effect on host cells?
- Attachment
- Cell entry
- Interaction with host cell
- Replication
- Assembly
- Release
What type of virus is HIV and therefore what enzyme does it contain?
HIV is a retrovirus so uses reverse transcriptase
Describe the structure of the HIV genome
Small RNA virus, expresses just 10 genes. It is a retrovirus and a lentivirus.
Which cells does HIV infect?
CD4+ cells (t-cells)
What receptor protein on HIV binds with the CD4?
gp120
Is it possible to be resistant to HIV?
YES! 1% of Caucasians are homozygous for a 32bp deletion in the CCR5 gene so they cannot be infected.
Why does HIV mutate and evolve rapidly?
Error-prone replication
Rapid viral replication
Large population sizes
Describe the majority of people currently with HIV
Living in sub-Saharan Africa
Heterosexual!
What are the UNIAIDS 90/90/90 Goals?
By 2020:
90% of those living with HIV are diagnosed
90% of those diagnosed are on ART
90% viral suppression for those on ART
Did we reach the UNIAIDS 90/90/90 goals?
Globally failed
In UK hit them in 2018
What is defined as late diagnosis of HIV?
When someone is diagnosed, their CD4 count is less than 350
Transmission routes of HIV
Blood
Sexual
Vertical (mum to baby)
Main forms of HIV prevention
ART
PrEP
PEP
Behaivoural
High risk groups for HIV
Men who have sex with men (MSM)
sub-Saharan African/Thailand
Multiple sexual partners
Rape in high prevalence localities
HIV symptoms
- Acute generalised rash
- Glandular fever
- Rash (involving palms)
- Indicators of immune dysfunction
- Unexplained weight loss or night sweats
- Recurrent bacterial infections (including p. pneumonia)
Who can offer a HIV test?
ANY healthcare professional
Which diseases does VSV cause?
Chickenpox (primary infection)
Shingles (secondary reactivation)
What is at the core of herpes viruses?
DNA genome
Difference between distribution of Smallpox and Chickenpox rashes
Smallpox tends to be at the periphery.
Chickenpox tends to be on the trunk.
Distributions of shingles rash
Dermatomal distribution. Most common in thoracic and ophthalmic divisions.
Treatment of secondary syphilis
Penicillin
Some rashes that effect the palms and soles of feet
HIV
Secondary syphilis
Hand, foot and mouth disease
Presentation of primary CMV (cytomegalovirus)
Similar to Epstein-Barre
Atypical lymphocytes
‘Owls eye’ intranuclear inclusions
