Med and Gen micro 2 Flashcards
3 potential modes of action of antibiotics?
Bacteriostatic - cell growth arrest, they stop growing, total and viable cell count go down
Bacteriocidal - viable cell count goes down, but total cell count stays the same
Bacteriolytic - reduction in total and viable cell count
What are macrolides?
Antibiotics which are mainly bacteriostatic
Stop protein synthesis
The macrolide binding site is the large ribosomal in the upper part of the nascent peptide exit tunnel
Easy passage of the newly made protein through the tunnel is crucial for bacterial protein synthesis
Macrolide binds and prevents translation
What are fluroquinolones?
Antibiotics that target DNA gyrase binding on to Topoisomerase II and IV
Get in via passive diffusion into Gram + and via outer membrane porins in gram -
What are Cephalosporins?
Bacteriocidal
Broad spectrum semi synthetic beta lactate antibiotic derived from the mould cephalosporin
Chemically related to penicillins
They interfere with bacterial cell wall synthesis
anti virulence strategies?
Inhibit specific mechanisms that promote infection and are essential to persistence in a pathogenic cascade and/or cause disease symptoms
Offer a reduced selection pressure for drug resistant mutations
UPEC (cause urinary tract infection) as an example of an anti virulence strategies?
Bacteria bind to cells using pilli
Invasion and replication
Biofilm formation
Biomass dispersion and cell exit
Spread to new cells
Type 1 Pilli and fimbriae are essential, and bind to manose on host cell
So can introduce a pillicide which gets rid of the pilli so can’t act on cell
Other anti virulence strategies?
Target Quorum sensing, can screen with GFP see what chemicals inhibit the AHL messenger signals being released
Targeting toxins, stop them being made transcribed, or use receptor mimics which prevent them binding to host cells
Inhibit secretion systems
Mechanisms of antibiotic resistance?
Drug inactivation using enzymes that modify or degrade the drug
Alteration of the drug target sites so can’t bind to target
Drug inaccessibility preventing entrance of the drug into the cell by modifying membrane permeability or transport systems
Drug efflux pumps pump the drug out of the cell
How are drug inactivated by enzymes made by bacteria example?
Penicillin breaks down cell wall by being a competitive inhibitor of transpeptidase so peptidoglycan cell wall can’t be cross linked and breaks down
Staphylococcus aureus produces penicillinase, so they made methicillin
But then the bacteria encoded for a variant penicillin binding protein (PBP) with a lower affinity for B-Lactams which would carry biosynthesis of the cell wall, so no B-lactams work anymore
Example of modification of the drug by enzymes?
An aminoglycoside is a protein synthesis inhibitor by targeting the 30S subunit
Modified by a phosphotransferase so doesn’t work
Produced by streptomyces
Not the only resistant mechanism, chromosomal acquired streptomycin resistance is frequently due to mutations in the gene encoding the ribosomal protein S12, rpsL
What is the major mediator of resistance to tetracycline which is a protein synthesis inhibitor that targets the 30S subunit?
Efflux pumps
How is anti biotic resistance spread?
Antibiotic resistance genes are present on chromosomes and R plasmids
Are transferred by vertical and horizontal transmission
There is selective advantage (natural selection) (vertical)
Horizontal, they don’t have to divide to pass genes on, this is done between mature cells via transformation, transduction and conjugation
Transformation is the Uptake of DNA from medium after being released from another, mediated by competence proteins
Transduction is the resistance gene is integrated into the new host cell chromosome or plasmid along with phage DNA
Conjugation is the resistance gene moves with the replicating plasmid into a new cell (R plasmids) through a pillus
What are phagocytes?
The professional phagocytes are the monocytes, macrophages, neutrophils, tissue dendritic cells and mast cells
Bacteria taken up by endocytosis and destroyed with phagolysosome
Mechanisms to counter bacteria that can counter phagocytosis and recognising bacteria in vesicles?
Done by Tol like receptors
They are in the cytoplasm for when the bacteria escape, and act as an alarm system
NLRs, Nod-like receptors, more than 20 have been described
Have a nucleotide-binding oliogomerization doman (NOD) and a number of LRRs (Leucine rich repeats)
Following the destruction of an ingested microbe by a phagocyte what happens?
They can then acts as antigen presenting cells (especially macrophages)
So its a link to the adaptive immune response
Peptides (can be a glycolipid) are on the outside of cell have diverse TCR bound to them and are recognised by T cells
Describe tuberculosis as a case study of the innate and adaptive response in disease control?
1/3 have it in us
It’s airborne
Prevalent in HIV individuals
So CD4 and CD8 are essential in protecting against it
Chest X-ray to determine infection
If adaptive immunity breaks down we can be reinfected via reactivation
Latent infection = Mtb containment in granuloma, higher chance of full infection later in life
Process of infection is macrophage takes it up, triggers innate system which draws in more immune system cells that surround it forming an innate granuloma, then T cells will come and surround forming an immune granuloma, the fibrotic encapsulation occurs forming a chronic granuloma, if the tb wins and it bursts causes death
Antibodies can have a role against tb
Cytokines have massive control in protecting against tb as they cause recruitment
What are biofilms and what problems do they cause?
Matrix associated microbial populations adherent to each other and or to surfaces or interfaces
Problems can occur when biofilms form on medical implants
Main infections caused by biofilms in tissues/fluids are?
Bacteremia (blood stream infection)
Urinary tract infections
Pneumonia
Why do we study biofilms?
Cause damage and disease
Act as reservoirs of contamination and infection
Difficult to control, require higher concentration of antibiotics
Are economically costly
What percentage of infections are biofilm related?
65%
What percentage of healthcare acquired infections?
60%
Biofilm microbial advantages?
Increased resistance to antimicrobial agents including antibiotics
Increased evasion of host defences. eg evasion of the immune system from TB (tubercle formation) intracellular salmonellae reduces capacity of it’s clearing by phagocytosis
Enhanced genetic interactions eg. movement of resistance plasmids
Stages of biofilm formation?
Free floating or planktonic bacteria encounter a submerged surface and within minutes can be come attached
EPS production allows the emerging biofilm community to develop a complex 3D structure
Biofilms can propagate through detachment of small or large clumps of cells or by a type of seeding dispersal that releases individual cells
How can biofilm bacteria move?
Collectively by rippling or rolling across the surface or by detaching in clumps
Or individually though swarming and seeding dispersal
Properties of biofilms and habitat formation?
Localized gradients eg. pH provides habitat diversity
Sorption for resource capture
Enzyme retention for external digestion system
Continuous regneration
Tolerance makes it act as a fortress
How does plaque form?
Primary colonisers on the surfaces including teeth and soft tissues
Secondary colonisers attach to primary colonisers
Maturation of plaque - growth in situ and attachment and detachment to the existing biofilm
Disease causation - pathogenic effects include the release of toxins/acids
3 main groups of plaque bacteria?
Aerobes:
High proportion of young plaque
Usually don’t cause harm
e.g. Neisseria subflava
Faculative anaerobes:
These are the majority of microbes in the mouth
Able to survive and grow with high/low oxygen concentrations
Usually gram positive
e.g. streptococcus mutans
Obligate anaerobes: High numbers in mature plaque O2 is toxic or inhibitory to growth Some of these species are harmful and may be associated with gum disease eg. Fusobacterium nucleatum
What are fungi?
Eukaryotic
Absorb nutrients by breaking down organic material into simple molecules
Types of colony?
Moulds - filamentous fungi
Yeast - predominantly unicellular
What do superficial mycoses infect?
Skin, hair, nails, mucous membranes
Eg. dermatophytes - athletes foot
Candida - Thrush
malassezia - dandruff or Pitryiasis versicolor
What do subcutaneous mycoses infect?
Through puncture wound
Rare infections, disease develops slowly
Very difficult to treat
Black moulds eg. chromoblastomycosis
Madurella mycetomatis - madura foot
What do deep seated / systemic mycoses infect?
Single deep organ or disseminated
2 groups of invasive mycoses?
Primary pathogens: (can cause disease in healthy people) Histoplasma capsulatum Blastomyces dermatitdis Parracoccidioides brasiliensis Coccidioides immitis
Opportunistic pathogens (only infect immunocompromised): Candida sp. Aspergillus sp. Cryptococcus sp. Pneumocystis jirovecii
both kill a lot of people
Features of Dermatophytes ( superficial mycoses)?
3 genera:
Microsporum sp.
Epidermophyton sp.
Trichophyton sp.
Filamentous fungi
From soil, animals and people
Produce keratinise:
Digest keratin as a growth substrate
Therefore infect keratin rich tissues
non mycological classification of dermatophytes?
Anthropophillic - host is man, eg. trichophyton - chronic athletes foot
Zoophillic - reservoir is animals, can infect man
produces the most severe inflammatory reaction
eg. microsporum canis in cats and dogs
Geophillic:
Found in soil, occasionally pathogenic
Features of Candida infections? ( superficial mycoses)
present in mouth, GI tract, women genital tract
Can infect normal people but infects more on people who are on antibiotics, diabetes or pregnancy
Features of primary pathogens? (fungi)
Infect healthy individuals
Route of infection is inflation of spores
Geographically limited - common in endemic regions
Histoplama infects 500,000 in US every year
All thermally dimorphic:
Saprophytic filamentous form at 25 degrees
Parasitic form at 37 degrees
Disease:
Asymptomatic
Mild respiratory infection
Can progress to be more lethal
Features of candida infections (deep-seated disseminated infections also is invasive and opportunistic )?
Single organ or widespread
Affects immunocomprimsed people who people have undergone surgery
Features of Candida auras an emerging pathogen?
FIrst reported in Japan 2009
Causes both superficial and systemic disease
Key concerns:
Multi drug resistant
Misdiagnosis
Hospital outbreaks
Features of Aspergillosis? (invasive and opportunistic)
Most don’t cause disease
Route of infection by inhalation of spores or sick building syndrome
Only 4 cause disease 200 don’t - A.fumigatus, A. flavus, A. niger and A. Terreus
Types of disease: Allergy TOxins in food Invasive bronchopulmonary Aspergillosis in immunocomprimsied Disseminated aspergillosis
Features of Cryptococcus sp. (invasive and opportunistic fungi)?
Cryptococcus neoformans and crypto coccus gattii are causative
Dimorphic
Capsulate yeast in clinical setting
Found in soil and avian habitats
Route of infection though inhalation and sexual cycle producing small spores
Disease:
Cryptococcosis
Meningitis
Features of Pneumocystis> (invasive and opportunistic pathogen)?
Causative version is pneumocystis jirovecii
Disease:
Pneumocystis pneumonia
Dry cough
AIDs defining disease
Route of infection through inhalation
We can’t culture it
Genome sequence:
Lacks genes for amino acids biosynthesis
So scavenges them from the host
Stages of candida infection?
Adhesion and colonisation
Epithelial penetration
Vascular dissemination (spreading in bloodstream)
Endothelial colonisation and penetration
