Emerging Pathogens Flashcards
Define emerging infectious diseases.
Infectious diseases that have newly appeared in a population or have existed but are rapidly increasing in incidence or geographic range or caused by one of NIAID category A,B,C priority pathogens
Define opportunistic infections.
Infections occurring due to bacteria, fungi, viruses or parasites that normally do not cause a disease but become pathogenic when body’s defense system is impaired
What are 3 reasons for pathogens emerging?
Development of new diagnostic tools
Increase in human exposure to bacterial pathogens
Emergence of more virulent bacterial strains & opportunistic infections
What is ‘one health’?
Integrated, unifying approach to balance & optimize the health of people, animals & environment
What are 4 examples of disease control & prevention?
Vaccination
Environmental sanitation
Vector control
Reduction of population growth
How are pathogens detected in pts?
Culture based
Microscopic examination
Molecular methods (PCR/NGS/MS)
What are 3 conventional techniques for environment screening?
Multiple tube fermentation
Membrane filters
Microscopic examination
What are 3 advanced techniques for environment screening?
Immunological methods (ELISA)
Molecular methods (PCR/FISH)
Enzymatic methods
Emerging methods (biosensors)
What is MALDI-TOF MS?
Matrix assisted laser desorption ionization-time of flight MS
What is MS?
Analytical approach that measures the mass-to-charge ration of compounds & calculates its exact molecular weight
What are 5 advantages of MALDI-TOF MS?
Fast diagnosis
Avoiding unnecessary antimicrobial use
Reduced morbidities & costs
Based on intact proteins
Low cost of analysis
What are 3 disadvantages of MALDI-TOF MS?
Trained laboratory personnel
Identification of new species relies strongly on complete database
Initial investment in expensive equipment
What are 6 characteristics of healthcare-associated-infections?
Unusual epidemiology & transmission
Medical environment
New infection sources & transmission ways
Another underlying disease
Strains emerging from microbiome
Subspecies level identification needed to define outbreaks & transmission
What are 3 examples of HAI?
MRSA
VRE
Multi-drug resistant E. Coli
What 4 pathogens are in the critical group of WHO bacterial priority pathogens?
Enterobacterales carbapenem - resistant
Enterobacterales 3rd gen cephalosporin resistant
Acinetobacter baumanii
Mycobacterium Tb rifampicin resistant
What are 2 characteristics of emerging respiratory tract pathogens?
Most common opportunistic pathogens in nosocomial infections
Developing a high level of Ab resistance that involves multiple mechanisms
What are the ESKAPE emerging respiratory tract pathogens?
Enterococcus faecium
Staphylococcus aureus
Klebsiella pneumoniae
Acinetobacter baumannii
Pseudomonas aeruginosa
Enterobacter spp.
What can MALDI-TOF MS be used for?
Identifying resistance
Growth of bacteria directly on MALDI-TOF MS target (4-5h)
Identification of spectra directly
What type of bacteria are emerging CF pathogens?
Opportunistic
Commensal
What are 6 emerging CF pathogens?
MRSA - easy transmission
Nontuberculous mycobacteria - ubiquitous environmental organisms eg. M. abscessus complex
Achromobacter spp. - environmental, rare opportunistic eg. A. ruhlandii
Stenotrophomonas maltophilia - aquatic environmental reservoirs
Pandoraea spp.
E.coli - no transmission
What are 7 characteristics of Mycobacterium abscessus?
Non-TB
Rapidly growing
Environmental (soil, water, animals, free living amoeba)
Opportunistic - concern in immunocompromised people
Increasing prevalence
Intrinsic & acquired resistance
IC proliferation & survival
What was M. abscessus historically considered as?
Environmental contaminant
What are 6 adaptations of M. abscessus?
Opportunity to colonise host
Adaptation to host environment -> pre-adaptation in amoeba & metabolic switch, genetics & acquirement of virulence factors
Developing transmission routes
Drug resistance
Niche specialisation
Dormancy
What 2 ways does M. abscessus spread?
Transformation in true pathogen
Inter-human transfer (direct/environmental)
What 2 pieces of evidence leads to evolution towards a pathogen?
Proof of person-to-person transmission
Proof of incidence in individuals with no known underlying conditions
What 3 things need to happen to lead to evolution towards a pathogen?
Pre-adaptation in environment
Intrinsic resistance to many Abs
Co-colonisation with other species of opportunistic bacteria (acquire new VFs)
What are 4 non-mycobacterial VFs?
Phospholipase C
MgtC
MsrA
ABC Fe(3+) transporters
What pathogen is the pharma industry becoming interested in?
Non-TB Mycobacteria
What is an example of an opportunistic pathogen?
Enterococcus spp
What are 3 sources of E. spp?
Gut colonization 7-10 days after birth
Adulthood sources - certain food
Environment - colonization of biotic & abiotic substances
What 4 infections can lead to pathogenic E. spp (mutagenic effects at sites of infection?
UTI
sepsis
ulcers
catheter related
What happens in dysbiosis of E. spp?
Enterococcal overgrowth in epithelial cell -> biofilm -> virulent
What are 5 commensal roles of E. spp?
Immune homeostasis
Produce bacteriocins against pathogens
Role in digestion
Block spread of putrefactive bacteria
Lower cholesterol levels
What are 5 sources of E. spp in probiotics?
Biotherapeutics for chronic sinusitis
Bio-preservatives
Dietary supplementation for animals
Starter cultures in dairy products
After antibiotics
When does E. spp become pathogenic?
Nosocomial infections
VF & resistance factors transmitted between species or genera by horizontal gene transfer
Food spoilage
Food poisioning
What are 6 therapy examples for emerging bacterial diseases?
Silver NPs
Antimicrobial light therapy
Antimicrobial peptides
Abs
Vaccines
Bacteriophage therapy
What are 4 characteristics of AMPs?
Short, +vely charged, amphiphilic, diverse
What are AMPs?
Host defense oligopeptides produced by all organisms
What are 2 factors of AMPs MoA?
broad spectrum of activity
interact with cell membrane - cell lysis
What are 8 mechanisms of synergy between AMPs & Abs?
Promoting bacterial absorption of Abs
Change membrane permeability
Interference with bacterial cell membrane
Target LPS in gram -ve bacteria
Destabilize LPS structure
Inhibit metabolic pathways
Inhibit drug resistant enzymes
Block efflux pumps
What are 6 AMPs advantages?
Unlikely to induce resistance
Broad range of action
Rapid bactericidal activity
Target poly-microbial infections
Improve action of Abs
Easy availability
What are 3 cons of AMPs?
Potentially toxic
Unstable in presence of proteases
Expensive to make
What are 4 light sources for ALT?
Xenon lamps
Light emitting diodes
Laser beams
Fiber optics
What type of wave length are preferred in ALT?
Longer - deeper tissue penetration
How does ALT work?
uses a photosensitizer (PS)—a light-activated compound—combined with a specific light source to generate reactive oxygen species (ROS)
What 5 things does ROS do to the bacterial cell?
Cell membrane disruption
Interrupted transmembrane electron transport
Damage to proteins
DNA damage
Damage to ribosomes
What are 5 characteristics of an ideal PS?
Strong absorption peak
Substantial triplet quantum yield
High tissue selectivity
No toxicity to human cells
High stability
What are 4 natural PSs?
Curcumin
Chlorophyll
Riboflavin
Chlorins
What are 5 advantages of ALT?
Broad spectrum of action
No resistance after multiple sessions
Used to support Ab therapy
Non-invasive
Low cost
What are 3 cons of ALT?
Sub-optimal uptake of PS by bacteria
Lack of selectivity
Short light penetration depths
How do silver NPs work?
Act by releasing Ag+ ions
Less reactive than silver ions
What are silver NPs action dependent on?
Physical, chemical, thermal, electrical & optical properties
(shape, size, concentration)
What do colloidal forms of AgNPs show?
Enhanced antimicrobial potential
What 4 ways are colloidal AgNPs synthesized by?
Chemical reduction
Physical
Biological
Green methods
What 4 things do the released Ag+ ions do?
Generate ROS
Disrupt electron transport & signal transduction pathways
Disrupt cell wall, cell membrane, cellular DNA & proteins
Inhibit planktonic cells & biofilms
What are 3 safety concerns of silver NPs?
Ag comparatively non- toxic/mutagenic compared to other metals
Resistance against AgNPs
Influence on microbiome
What 3 things can AgNPs do to cells?
Carcinogenesis & fibrosis
Genotoxicty
Cytotoxicty
What have AgNPs been used for?
Prevention on infection
CF inhalation therapy
M. TB, M. bovis & multiple drug resistant TB strains
What are 4 potentials of AI for emerging pathogens?
Combating Biofilm formation
Ab discovery
De novo drug designing
Detection & monitoring
What are 3 current applications of AI?
Interpretation of antimicrobial susceptibility profiles - neural-network based app
In silico drug design approaches for structure & ligand based design
Virtual screening of drug candidates
