Community and hospital acquired bacterial infections - 03.03.2020 Flashcards
What are Important bacterial virulence factors?
Diverse secretion systems Flagella Pili Capsule Endospores Biofilms Exotoxins Endotoxins
Define an outbreak of infectious disease
An outbreak is a greater than normal or greater than expected number of individuals infected or diagnosed with a particular infection in a given period of time or a particular place, or both.
Explain how outbreaks are identified
surveillance systems provide and opportunity to identify outbreaks
Good and timely reporting systems are instrumental to identify outbreaks.
It is important to find the source where the infection came from.
List bacterial pathogens that cause community acquired infections (in Europe)
- Influenza
Explain the route and type of infection caused by these bacterial pathogens
x
Exotoxins
- Neurotoxins (act on nerves or motor endplate)
i. e. Tetanus or Botulinum toxins - Enterotoxins (act on the GI tract)
1) Infectious diarrhea i.e. Vibrio cholera, Escherichia coli, Shigella dysenteriae and Campylobacter jejuni
2) Food poisoning i.e. Bacillus cereus or Staphylcoccus aureus - Pyrogenic exotoxins (stimulate release of cytokines) i.e. Staphylcoccus aureus or Streptococcus pyogenes
- Tissue invasive exotoxin ((allow bacteria to destroy and tunnel through tissue) enzymes that destroy DNA, collagin, fibrin, NAD, red or white blood cells, i.e. Staphylococcus aureus, Streptococcus pyogenes, Clostridium perfringens)
- Miscellaneous exotoxins ((specific to a certain bacterium and/or function not well understood)
i. e. Bacillus anthracis and Corynebacterium diphtheriae)
ENDOTOXINS
- > only found in gram -ve bacteria; outer membrane , lipid A part of LPS
- > not a protein, LPS from gram -ve bacteria
HUS
- haemolytic ureic syndrome
- characterised by a triad of acute renal failure, haemolytic anemia and thrombocytopenia
- EHEC eccoli strain
susally found in children and usually caused by the shiva toxin producing e, coli - through ingestion of focal matter
- usually quite rare but in the outbreak in 2011 aaa few people had it.
How does shiga toxin work?
- AB5 subunit composition
- shuts down protein synthesis in eukaryotic cell
- also affects several other cellular processes
- might affect the commensal microflora in the gut.
Shiga toxin gene transfer
Shiga toxin on a phage -> makes it easier to infect other strains.
- Shiga toxins are encoded on a bacteriophage
- highly mobile genetic elements and contributes to horizontal gene transfer
- Toxins are highly expressed when the lytic cycle of the phage is activated
Name some pathogenic bacteria
enteropathogenic E. coli (EPEC) enterotoxigenic E. coli (ETEC) enterohaemorrhagic E. coli (EHEC) diffusely adherent E. coli (DAEC) enteroaggegrative E. coli (EAEC) enteroinvasive E. coli (EIEC) uropathogenic E. coli (UPEC) neonatal meningitis E. coli (NMEC)
What does virulence of E. coli depend on?
- the genes they have acquired
- e.g. aggregative adherence fimbriae (AAF)
Fimbriae
- an appendage that can be found on many Gram-negative and some Gram-positive bacteria, that is thinner and shorter than a flagellum.
- also referred to as an “attachment pilus” by some scientists
- Fimbriae are one of the primary mechanisms of virulence for E. coli, Bordetella pertussis, Staphylococcus and Streptococcus bacteria.
- Their presence greatly enhances the bacteria’s ability to attach to the host and cause disease.
What is the difference between endo- and exotoxins?
- exotoxins are proteins
- endotoxins are lipid A from LPS on gram -ve bacteria
Communicable disease in Europe - main groups
1) Respiratory tract infections
2) Sexually transmitted infections, including HIV and blood-borne viruses
3) Food- and waterborne diseases and zoonoses
4) Emerging and vector-borne diseases
5) Vaccine-preventable diseases
6) Antimicrobial resistance and healthcare-associated infections
Bacterial Respiratory tract infections
(Influenza, Animal influenzas, including avian influenza, SARS - Severe acute respiratory syndrome)
Legionnaires’ disease (legionellosis)*
- Legionella pneumophila (Gram -)
Tuberculosis*
- Mycobacterium tuberculosis (Gram +)
Legionnaires’ disease (legionellosis)
- Gram-negative bacterium
- Lives in amoeba in ponds, lakes, air conditioning units, whirlpools,…
- Infection route: inhalation of contaminated aerosols
- In humans L. pneumophila will infect and grow in aveolar macrophages
- Human infection is “dead end” for bacteria
- Important virulence factor type IV secretion system
Type 4 secretion system
- injects toxin proteins from cytoplasm of cell to outside)
- allow Legionella to replicate in a Legionella containing vacuole (LCV)
Mycobacterium tuberculosis
- groups with gram-positive bacteria
- very different cell wall – extra lipid layer makes treatment more difficult
- antibiotic treatment for 6 months
- 72% success rate of treatment, recurrence may lead to MDR
- MDR TB treatment success rate is 32%
- M. tuberculosis can enter a dormant state: Latent TB - evidence of infection by immunological tests but no clinical signs and symptoms of active disease
2) Sexually transmitted infections,
including HIV and blood-borne viruses - examples
- Chlamydia trachomatis infection *
- Gonorrhoea* (neissera gonorrhoea)
- Hepatitis B virus infection
- Hepatitis C virus infection
- HIV/AIDS
- Syphilis*
Bacterial STIs
- Chlamydia trachomitas infection
- gonorrhoea (neissera gonorrhoea)
- Syphilis
Chlamydia trachomatis
- obligate intracellular pathogen
- cannot culture it outside host cell
- Most frequent STI in Europe 410.000 cases/year
Infection likely higher due to underreporting - Other parts of the world:
Eye infection: - 84 million people infected and about 8 million visually impaired.
- It is responsible for more
than 3% of the world’s blindness
Neisseria gonorrhoeae - facts and important virulence factors
- can change surface coat
- Gram- negative diplococcus
- Establishes infection in the urogenital tract by interacting with non-ciliated epithelical cells
Important virulence factors and traits:
- pili and
- antigenic variation
- escape detection and clearance by the immune system
3) bacterial Food- and waterborne diseases and zoonoses
MAIN:
- cholera
- campylobacter
- listeria
- salmonella
- Anthrax (+ Bacillus anthracis -hoofed animals i.e. sheep, cattle, and goats,
but humans who come into contact with infected animals can get sick ) - Botulism (+ Clostridium botulinum - through wounds, canned/preserved food)
- Brucellosis (– Brucella spp. caused by ingestion of unsterilized milk or meat)
- Campylobacteriosis (Campylobacter sp. mostely C. jejuni)
- Cholera (- Vibrio cholera)
- Infection with Vero/shiga toxin-producing Escherichia coli (Gram negative)
- Leptospirosis (- Leptospira spp.)
- Listeriosis (+ Listeria monocytogenes)
- Salmonellosis (- Salmonella sp.)
- Shigellosis (- Shigella sp.)
- Tularaemia (- Francisella tularensis)
Typhoid/paratyphoid fever (Salmonella typhi and S. Paratyphi) - Yersiniosis (- Yersinia enterocolitica)
Campylobacter
- Most commonly reported infectious GI disease in the EU
- Usually sporadic cases and not outbreaks
- Small children 0-4 years – highest risk group
- Infection most likely through undercooked poultry
Virulence factor:
- Adhesion and Invasion factors,
- Flagella motility,
- Type IV Secretion system
- Toxin
Type 3 secretion system
needle with which bacteria can inject toxins
vibrio cholerae
- Cholera is an acute, severe diarrhoeal disease
- Without prompt rehydration, death can occur within hours of the onset of symptoms
- cholera toxin makes it so pathogenic acquired via phage
- type IV fimbria
Cholera toxin
- AB5 multimeric protein complex
- secreted by the bacterium vibrio cholerae
- CTX is responsible for the massive, watery diarrhoea characteristic of a cholera infection
- pump out Cl-, water follows
- It is a member of the Heat-labile enterotoxin family.
Listeria monocytogenes
Risk group:
- immune compromised, pregnant and their fetus, elderly
- Listeria can enter non-phagocytic cells and cross three tight barrie:
- Intestinal barrier, BBB and Materno-fetal barrier
- Instrumental for our current understanding of fundamental concepts in cell biology such as actin based cell mobility
- Great importance in the field of immunology MHC class I presentation
4) Emerging and vector-borne diseases (bacterial)
Plague (yersinia pestis gram -ve)
Q-fever (coxiella burnettii gram -ve)
5) Vaccine preventable bacterial diseases
- diphtheria
- pertussis
- tetanus
- …..
What is an antimicrobial
interferes with growth and reproduction of a ‘microbe’
What is an antibacterial
commonly used to describe agents to reduce or eliminate harmful bacteria
What is an antibiotic
- a type of antimicrobial
- used as medicine for humans, animals
- originally referred to naturally occurring compounds
- now there are many synthesised antibiotics
- still looking for not yet discovered antibiotics in nature
What is a HAI?
- Healthcare-associated infections (HAI) are infections that occur after exposure to healthcare
- Infections starts > 48 after admission to the hospital
- 3.2 million patients acquire a healthcare-associated infection in the EU each year (1 in 18 patients acquires an health care associated infection every day)
- About 37.000 of them die as the direct consequence of the infection.
- The most frequent types of HAI are surgical site infections, urinary tract infections, pneumonia, bloodstream infections and gastrointestinal infections.
Most common types of HAI
- surgical site infections
- urinary tract infections
- pneumonia
- bloodstream infections
- gastrointestinal infections.
Effect of hospital acquired infection on
length of stay
- longer stay
- estimated extra cost of £1 billion
Hospitals as a source of infection
Intervetnion:
- Chemotherapy
- intubation
- prosthetic material
- catheters
- prophylactic antibiotics
- lines (central, i.v., arterial, CVP/pulmonary A)
Dissemination:
- hygiene measures
Concentration
- many people on wards
Most common HAI bacterial pathogens previosly
ESKAPE
- Enterococcus faecium
- Staphylococcus aureus
- Klebsiella pneumoniae
- Acinetobacter baumanii
- Pseudomonas aeruginosa
- Enterobacter species
Most common HAI bacterial pathogens now
ESCAPE
Gram +
- Enterococcus faecium
- Staphylococcus aureus
- Clostridium difficle
Gram -
- Acinetobacter baumanii
- Pseudomonas aeruginosa
- Enterobacteriaceae (- pathogenic E. coli, Klebsiella pneumoniae, Enterobacter species.
What are the major resistance problems in the ESCAPE pathogens?
- Enterococcus faecium (vancomycin resistance)
- Staphylococcus aureus (methicillin resistant - MRSA)
- Clostridium difficile (can establish infection because of previous antibiotic treatment) - due to AB treatment there is and advantage
- Acinetobacter baumanii (highly drug resistant)
- Pseudomonas aeruginosa (multi drug resistant i.e fluoroquinolone-resistant)
- Enterobacteriaceae
- pathogenic E. coli (multi drug resistant)
- Klebsiella pneumoniae (multi drug resistant)
- Enterobacter species (multi drug resistant)
Pathogenic E. coli
- Most frequent cause of bacteraemia by a Gram-negative bacterium
- Most frequent cause of community and hospital acquired UTI
- Increase in MDR strains
- Occurrence of resistance to 3rd generation cephalosporsins as high as 20% in some countries
- Most isolates that are resistance to cephalosporin express the extended spectrum beta lactamase (ESBL)
- Still sensitive to carbapenems
Cephalosporins
- are a class of b-lactam antibiotics
(- have a beta-lactam ring) - Target pathway: Inhibit peptidoglycan synthesis
- Target protein; Inhibit the activity of penicillin binding
proteins (PBPs)
Resistance:
- Extended spectrum b-lactamase (ESBL)
- encoded on a plasmid
- Mobile
- ESBL enzyme cleaves cephalosporin
Resistance to cephalosporins
- Extended spectrum b-lactamase (ESBL)
- encoded on a plasmid
- Mobile
- ESBL enzyme cleaves cephalosporin
Carbapenems
- are a class of b-lactam antibiotics
- Target pathway: Inhibit peptidoglycansynthesis
- Target protein
Inhibit the activity of penicillin binding proteins (PBPs)
Resistance to carbapenems
- carbapenemase enzyme,
blakpc encoded on a tranposon mobile genetic element - enzyme cleaves carbapenem
MRSA
- MRSA is the most important cause of antimicrobial resistant infection worldwide
- methicillin resistant S. aureus (MRSA)
Methicillin
- beta lactam
- target pathway: inhibit peptidoglycan synthesis
- target protein: inhibit the activity o penicillin binding proteins (PBSs)
Methicillin resistance
- Expression of additional
penicillin binding protein - PBP2A has low affinity for methicillin and can still function
in the presence of the antibiotic - MRSA strains can synthesis peptidoglycan and survive in the presence of methicillin
VRE
- vancomycin resistant enterococcus faecium
- 3rd most frequently identified cause of nosocomial blood stream infections (BSI) identified in the US
- Vancomycin resistance is around 60%
Vancomycin
Target pathway: Inhibit PG synthesis
Target: binds to PG precursor
Vancomycin resistance
multiple proteins
genes encoded on plasmid or transposon
Results in the synthesis of a different PG precursor
Name three factors,which can contribute the acquisition of hospital acquired infections
- dissemination
- concentration
- Intervention (catheter, intubation etc.) -> you need the interventions however there is a risk.
Cephalosporin is a beta lactam AB and resi
true
Methicillin and carbapenem
are both beta-lactam antibiotics
true
Carbapenem resistance is frequently found in
Klebsiella pneumoniae - t/f?
true
Shape/form of bacteria
Bacteria come in lots of shape and forms. Sometimes you can determine the type of infection by the shape of the bacteria:
• Cocci – coccus, diplococcus
(+encapsulated), staphylococci, streptococci, sarcina, tetrad
• Bacilli – coccobacillus, bacillus, diplobacilli, palisades, streptobacilli
• Budding + appendaged bacteria – hypha, stalk
• Other forms – enlarged We must remember that bacteria do not always cause infection, many are commensal
Bacterial components
Prokaryotes, with a cytoplasm with no organelles
Circular DNA + cytoplasmic ribosomes
Surrounding by a plasma membrane + capsule, often with many external structures
Capsules as virulence factors
(protect against phagocytosis)
i.e. Streptococcus pneumoniae
Pili as virulence factors
important adherence factors
Flagella as virulence factors
(movement, attachment)
Endospores as virulence factors
(metabolically dormant forms of bacteria)
heat, cold, desiccation and chemical resistant
i.e. Bacillus sp. and Clostridium sp.
Biofilms as virulence factors
Biofilms (organized aggregates of bacteria embedded
in polysaccharide matrix – antibiotic resistant)
i. e. Pseudomonas aeruginosa
i.e. Staphylococcus epidermidis
What are the different types of exotoxins?
Neurotoxins Enterotoxins Pyrogenic exotoxins Tissue invasive exotoxins Miscellaneous exotoxins
Neurotoxins
- act on nerves or motor endplate
- cause paralysis
i.e. Tetanus or Botulinum toxins
Enterotoxins
(act on the GI tract)
1) Infectious diarrhea
i. e. Vibrio cholera, Escherichia coli, Shigella dysenteriae and Campylobacter jejuni
2) Food poisoning
i. e. Bacillus cereus or Staphylcoccus aureus
Pyrogenic exotoxins
(stimulate release of cytokines)
i.e. Staphylcoccus aureus or Streptococcus pyogenes
Tissue invasive exotoxins
Tissue invasive exotoxin (allow bacteria to destroy and tunnel through tissue) enzymes that destroy DNA, collagin, fibrin, NAD, red or white blood cells
i.e. Staphylococcus aureus, Streptococcus pyogenes. Clostridium perfringens
Miscellaneous exotoxins
(specific to a certain bacterium and/or function not well understood)
- i.e. Bacillus anthracis and Corynebacterium diphtheriae
Endotoxins
- Only produced by Gram-negative bacteria
- Not a protein but the lipid A moiety of LPS
- Shed in steady amounts from living bacteria
- Treating a patient who has a Gram-negative infection with ABs can sometimes worsen condition
- when bacteria lyse they release large quantities of LPS/ Endotoxin -> Septic shock (drop in BP and organ dysfunction) also called endotoxic shock
Septic shock
- Sepsis that results in dangerous drops in BP and organ dysfunction is called septic shock.
- also referred to as endotoxin shock because endotoxin often triggers the immune response that results in sepsis and shock.
- But you should remember that also different effectors molecules in Gram-positive bacteria or even fungi can trigger this adverse immune response – so the term septic shock is inclusive
EAEC virulence factor: aggregative adherence fimbriae (AAF)
- genes encoding for AAF are on a plasmid mobilized between strains
- AAF required for adhesion to enterocytes
- AAF stimulate a strong IL-8 response allowing biofilm formation
- Additional virulence factors lead to the disruption of actin cytoskeleton -> exfoliations
Name 3 differentbacterial virulence factorsand describe their function
x
see mindmap
Type 3 and Type 4 secretion systems
- Type III secretion system use a process which injects the secretory molecule into the host cell.
- Type IV secretion systems use a process which is similar to the bacterial conjugation machinery.
- Type IV secretion systems require attachment to the host cell by direct cell-to-cell contact or via a bridge-like apparatus.
- Type IV secretion systems can be used to both transport and receive molecules.
- Type III secretion systems requires a large protein complex to ensure proper transfer of secretory molecules.
Salmonella
- One of the most common GI infections in the EU
- Undercooked poltry
- Outbreaks
- Highest infection rate in small children (0-4 years)
- Important virulence determinant
- Type III secretion systems encoded on pathogenicity islands (SPI)
Salmonella enterica
Type III secretion system
SPI1: is required for invasion
SPI2: intracellular accumulation
Antimicrobial vs antibacterial vs antibiotic
Antimicrobial
- interferes with growth & reproduction of a ‘microbe’
Antibacterial
- commonly used to describe agents to reduce or eliminate harmful bacteria
Antibiotic is a type of antimicrobial
- used as medicine for humans, animals originally referred to naturally occurring compounds
Klebsiella pneumoniae and resistance
- Important cause of UTI and respiratory tract infections
- Risk group: immuno compromised
- High proportion of resistance to 3rd generation cephalosporins, fluroquinolones and aminoglycosides
- carbapenem-resistant Klebsiella pneumoniae (CRKP) is the species of CRE most commonly encountered in the United States
Pseudomonas aeruginosa and resistance
- Important cause of infection in immuno-compromised
- High proportions of strains are resistant to several antimicrobials
- In ½ of EU countries resistance to carbapenems is above 10%
MRSA
MRSA is the most important cause of antimicrobial resistant infection worldwide
methicillin resistant S. aureus
