mini mod.: medical microbiology Flashcards
factors contributing to infectious process
what is epidemiology
factors:
hosts, microorganisms and environment (all a spectrum)
together cause infection
epidemiology-diagnosis, treatment and prevention of infectious disease
study of:
the nature, distribution, causation, transfer, prevention and control of disease
The impact of epidemiology and understand disease/death
infection causes-1.7 billion deaths(20th century)
Major global bacterial diseases - key egs:
Respiratory - mycobacterium tuberculosis
Diarrheal- Vibrio cholerae
Infections involve:
Host, microorganisms and environmental interactions
Epidemiology-the nature of (human) infection
Bacterial infection threats?
Antibiotic resistance, reduced vaccination rates and poverty
Understand different types bacterial pathogen (and know examples)
pathogen definition: a microbe capable of causing host damage and disease
opportunistic pathogen:
capable of causing damage and infection in a compromised host.
examples:
Pseudomonas aeruginosa -
-Gram negative
-Phylum: proteobacteria
-Class: Gammaproteobacteria
Staphylococcus aureus -
-Gram positive
-Phylum:Firmicutes
-Class:Bacilli
obligate pathogen:
causes damage and infection as part of its growth and replication
example: Mycobacterium tuberculosis -
-Taxonomically Gram-positive
-Aerobe
-Phylum: Actinobacteria
facultative pathogen:
causes disease as one part of its life cycle or when in a different host
example: Vibrio cholerae
-Gram-negative
-Anaerobe
-Phylum: proteobacteria
-Class: Gammaproteobacteria
commensal pathogen:
induces either no damage or clinically inapparent damage to the host but may elicit an immune response
example: Epithelial or gut bacteria:
Lactobacillus acidophilus
-Gram positive
-Phylum:Firmicutes
-Class:Bacilli
identifying medically relevant bacteria
conventional baceriology; largely based on growth of organisms
molecular diagnostics-increasing culture-independant strategies (eg. PCR & direct DNA sequencing from samples; microbiome analysis)
How do we identify bacterial pathogens?
species level identification: first step in infectious diagnostics
sequence-based strain genotyping gives the highest resolution
identification and genotyping: is & will become genomics driven
Isolate > Strain > Species concepts
Isolate cultured from an infection (or elsewhere); no genetic knowledge
Strains are defined
when there is some knowledge of clonality
or genetic identity
* Ribotyping
* Macrorestriction & PFGE
* PCR-fingerprinting
* DNA sequencing
Species consist
of large numbers of strains which share similar phenotypic and genetic properties
* 16S rRNA gene (>97% identity)
* gyrB or recA gene
* >70% DNA-DNA hybridisation
* Average nucleotide identity
Examples of strain tracking & genotyping
PCR genotyping
pulsed-field gel electrophoresis(PFGE) macrorestriction typing
^both have limited resolution
DNA sequence-based genotyping has resolution at all taxanomic levels
Multilocus sequence typing (MLST)
* Initially PCR based (1998)
* Sequence several conserved genes
* Approx. 500 bp from a PCR fragment
* Define genetic linkage between strains
* Globally searchable strain databases
Bacterial virulence factors (& research example)
definition of a virulence factor:
drives a mechanisms or process of infection
aids host colonisation
allows immune evasion
host cell invasion or escape
host destruction
nutrient scavenging
poisoning
virulence factors:
adhesins eg. pili
endotoxin eg. glycolipids
exotoxin eg. botuinum
nutrient acquisition eg. siderophores(iron binding)
destructive enzymes eg. lipase/protease
intracellular entry eg. invasins
immune minicry eg. capsule antigens
Define the microbiome
host
ecological niche
commensal
mutualism
Micro biome- entire habitat, including the microorganisms, their genomes and surrounding environmental conditions
Host-any organism that harbours other organisms
Ecological niche-functional role on organisms plays within an ecosystem
Symbiotic relationships:
Commensal-a relationship where one organism benefits and the other is unaffected
Mutualisms-a mutually beneficial relationship between 2 organisms
Critically evaluate the concepts of commensalism and pathogenicity
spectrum of pathogenicity:
commensal->opportunistic pathogen->obligate pathogen
commensal-does not cause infection and may be beneficial
opportunistic pathogen-can cause infection
obligate pathogen-will always cause infection
why is the microbiome important when considering pathogenicity:
* Reservoir of opportunistic pathogens
* Reservoir of genes
* Source of antimicrobials and stimulatory components
* Interacts with the host
Consider how microbes may have both a positive or negative effect on the host in different situations
gut microbiome: healthy and dysbiosi=opposite
healthy-high:
diversity and righness
symbionts
colonisation resistance
low:
pathogens/pathobionts
immunogenicity
Define antimicrobials vs antibiotics
anitmicrobials:
* Synthetic or natural compounds which exhibit selective toxicity by inhibiting microbial pathogens without adversely affecting the host.
* Classified according to similarities in:
1. Molecular structure
2. Mechanism of action
3. Spectrum of antimicrobial activity
* Although thousands of antibiotics are known, <1% are clinically useful due to toxicity to the host or lack of uptake by host cells.
antibiotics:
* Antibiotics are antimicrobial agents that are produced naturally by microorganisms such as certain species of bacteria and fungi.
* Susceptibility of bacteria to different antimicrobial agents varies significantly due to their differing modes of action.
* Some antibiotics exhibit narrow spectrum activity, whereas others exhibit broad-spectrum activity.
* This is dependent upon whether the target is present in only certain types of bacteria (e.g. Gram positive or Gram negative), or in all.
Describe some of the common cellular targets of antibiotics
targeting cell wall:
* Cell wall synthesis inhibitors include β- lactam antibiotics such as penicillins and cephalosporins.
* These antibiotics possess a β-lactam ring
* This interferes with transpeptidation, a reaction which results in the cross-linking of two glycan-linked peptide chains, leading to peptidoglycan synthesis.
* Penicillin G is primarily active against Gram positive bacteria
* Semi-synthetic penicillins include ampicillin
nucleic acid synthesis inhibitors:
* Quinolones disrupt bacterial metabolism by interfering with bacterial DNA gyrase, preventing the supercoiling of DNA.
* This is an essential step required to package DNA within all bacterial cells.
* Fluoroquinolones are therefore effective against both Gram positive and Gram negative bacteria.
* An example is ciprofloxacin, used to treat urinary tract infections in humans as well as in the beef and poultry industries to prevent and treat respiratory diseases in animals.
protein synthesis inhibitors:
* Inhibit protein translation via ribosomes
* Aminoglycosides, e.g. kanamycin, streptomycin, gentamycin
- Bind with high affinity to the 30S ribosomal subunit, resulting in the ribosome misreading mRNA, leading to error-filled proteins
* Tetracyclines have a similar mode of action to aminoglycosides
* Macrolides, e.g. erthyromycin, azithromycin
- Bind to the 50S ribosomal subunit causing partial inhibition of protein synthesis and resulting in an imbalance in the proteome
Consider how microbes develop resistance to antibiotics both genetically and behaviourally
These fall into 6 categories:
1. Modification of the drug target
2. Enzymatic inactivation
3. Removal from the cell through efflux pumps
4. Metabolic bypassing
5. Decreased uptake
6. Lifestyle changes: growing as a biofilm
* Some bacteria may be intrinsically resistant to certain antimicrobial drugs as they naturally lack the target.
* Others may become resistant through random chromosomal mutation or acquiring resistance genes from the environment or from other bacteria.
