Med and Gen micro 2 Flashcards

1
Q

3 potential modes of action of antibiotics?

A

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

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2
Q

What are macrolides?

A

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

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3
Q

What are fluroquinolones?

A

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 -

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4
Q

What are Cephalosporins?

A

Bacteriocidal

Broad spectrum semi synthetic beta lactate antibiotic derived from the mould cephalosporin

Chemically related to penicillins

They interfere with bacterial cell wall synthesis

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5
Q

anti virulence strategies?

A

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

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6
Q

UPEC (cause urinary tract infection) as an example of an anti virulence strategies?

A

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

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7
Q

Other anti virulence strategies?

A

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

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8
Q

Mechanisms of antibiotic resistance?

A

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

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9
Q

How are drug inactivated by enzymes made by bacteria example?

A

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

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10
Q

Example of modification of the drug by enzymes?

A

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

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11
Q

What is the major mediator of resistance to tetracycline which is a protein synthesis inhibitor that targets the 30S subunit?

A

Efflux pumps

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12
Q

How is anti biotic resistance spread?

A

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

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13
Q

What are phagocytes?

A

The professional phagocytes are the monocytes, macrophages, neutrophils, tissue dendritic cells and mast cells

Bacteria taken up by endocytosis and destroyed with phagolysosome

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14
Q

Mechanisms to counter bacteria that can counter phagocytosis and recognising bacteria in vesicles?

A

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)

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15
Q

Following the destruction of an ingested microbe by a phagocyte what happens?

A

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

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16
Q

Describe tuberculosis as a case study of the innate and adaptive response in disease control?

A

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

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17
Q

What are biofilms and what problems do they cause?

A

Matrix associated microbial populations adherent to each other and or to surfaces or interfaces

Problems can occur when biofilms form on medical implants

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18
Q

Main infections caused by biofilms in tissues/fluids are?

A

Bacteremia (blood stream infection)

Urinary tract infections

Pneumonia

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19
Q

Why do we study biofilms?

A

Cause damage and disease

Act as reservoirs of contamination and infection

Difficult to control, require higher concentration of antibiotics

Are economically costly

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20
Q

What percentage of infections are biofilm related?

A

65%

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21
Q

What percentage of healthcare acquired infections?

A

60%

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22
Q

Biofilm microbial advantages?

A

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

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23
Q

Stages of biofilm formation?

A

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

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24
Q

How can biofilm bacteria move?

A

Collectively by rippling or rolling across the surface or by detaching in clumps

Or individually though swarming and seeding dispersal

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25
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
26
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
27
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 ```
28
What are fungi?
Eukaryotic Absorb nutrients by breaking down organic material into simple molecules
29
Types of colony?
Moulds - filamentous fungi Yeast - predominantly unicellular
30
What do superficial mycoses infect?
Skin, hair, nails, mucous membranes Eg. dermatophytes - athletes foot Candida - Thrush malassezia - dandruff or Pitryiasis versicolor
31
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
32
What do deep seated / systemic mycoses infect?
Single deep organ or disseminated
33
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
34
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
35
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
36
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
37
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
38
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
39
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
40
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 ```
41
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
42
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
43
Stages of candida infection?
Adhesion and colonisation Epithelial penetration Vascular dissemination (spreading in bloodstream) Endothelial colonisation and penetration
44
Is Candida albicans virulence multi-factorial?
Yes
45
Important virulence factors of Candida albicans?
``` Adhesion to host surfaces Invasion of epithelial Penetration beyond epithelia Obtaining nutrients Opposing host defences ```
46
Host defences against Candida albicans?
Flushing mechanisms Molecular recognition Phagocytosis and killing Immune response
47
Basic properties of Candida albicans?
Diploid organisms - 8 chromosomes Largely asexual Polymorphic fungus CUG codon reassigned
48
Main forms C.albicans can take?
``` Yeast - buds Pseudohyphae - buds mixed with hyphae Hyphae - long filaments Opaque - see through buds Chlamydospore - branch of from hyphal cells, tough cell at end, form in nutrient poor environments ```
49
What is hyphal growth promoted by?
``` Temperature above 35 degrees Serum Neutral pH High pCO2 Low O2 Nitrogen or carbon starvation Matrix embedded growth ``` Quorum sensing: High cell densities causes hyphal growth
50
What allows candida to adhere?
Manoproteins on cell surface Als3 is very important
51
What does candida normally infect?
``` Invades normally non-phagocytic host cells Invasion generally hyphal specific 2 main routes: Induced endocytosis Active penetration ```
52
Describe candida invasion via induced endocytosis?
Fungal invasion interacts with host cell surface proteins Interaction triggers final engulfment through endocytosis 'zipper like' mechanisms
53
Describe candida invasion via active penetration?
Pushes itself into host cells or between junctions potentially involves: Physical force from directional growth and turgor pressure Secreted hydrolytic enzymes degrading host tissue
54
Describe C.albicans forming biofilms?
Form on a variety of biotic and abiotic surfaces Structured assemblies encased in extracellular matrix Display inherent resistant to antifungals and host defences Quorum sensing and polymicrobial interactions impact on formation
55
Stages of biofilm formation of C.albicans?
Attachment - adherence of yeast cells to substrate Initiation - formation of micro-colony Maturation - hyphal development and ECM production Dispersal - release of non adherent yeast cells
56
What does C.albicans secrete to aid its virulence?
Hydrolytic enzymes play a role in obtaining nutrients, combatting host defence and adhesion
57
How does C.albican obtain Iron from host because it's limited?
Reductive pathway Siderophore uptake Haemoglobin uptake and degradation
58
What stresses does the immune system cause to Candida which candida also can detect through pathways?
Phagocytosis: Change in pH Low amino acid availability Lack of glucose and iron ``` Respiratory burst (rapid release of reactive oxygen species ): Reactive oxygen and nitrogen species ``` Cytokine burst: Inflammatory response Elevated temperature
59
5 types of anti fungal agents?
Membrane disrupting agents: Polyenes Ergosterol synthesis inhibitors: Azoles, allylamines DNA synthesis inhibitors: Flucytosine Glucan synthesis inhibitors: Echinocandins
60
Describe Polyenes?
Associate with ergosterol to form pore structures Cause membrane leakage Cause cell death (fungicidal) ``` Examples are: Amphotercin B (AmB), and nystatin ``` Wide spectrum Not available orally - only used in hospital Only problem is nephrotoxicity - damage of the kidney
61
What is ergosterol?
Fungi version of cholesterol in mammals So it stabilises the phospholipid bilayers They are so similar its difficult to not harm host cells when using drug
62
Describe the Azoles?
Synthetic compound Contain Azole rings - used now is triazoles (3 nitrogens) Examples are Fluconazole, Voriconazole, and Isavuconazole Inhibit ergosterol synthesis by inhibiting 14a sterol demethylase which blocks heme iron in the enzyme This alters membrane fluidity due to build up of 14a sterols Broad spectrum Problems: Drug interactions - enzyme related cytochrome P450 which is used in human liver in drug metabolism Resistance forms
63
Describe the Allyamines?
Synthetic compound Inhibits ergosterol biosynthesis Cells accumulate squalene which kills them Fungicidal against dermatophytes and poor activity against other species
64
Describe 5-flucytosine?
Example is 5-Flucytosine - (initially a anti cancer treatment) Enters fungal cells via cytosine permease - converted to 5 fluorouracil which insist protein synthesis and DNA syntheses Only works on yeast Resistance is very common so used very often
65
Describe Echinocandins?
Semisynthetic Inhibit B1, 3-Glucan synthase which is essential component of cell wall Fungicidal against candida Fungistatic against aspergillus No problem of cross resistance and aren't very toxic Problems: Not available orally and are expensive
66
What is primary/natural resistance?
Intrinsic resistance - naturally doesn't work on them
67
What is secondary resistance?
Susceptible strainbecomes resistant through mutation and selection - (in fungi horizontal gene transfer can't occur)
68
Mechanism of resistance against Amphotercin?
Reduced ergosterol content Alteration of sterol/phospholipid balance Increased catalase activity to combat oxidative stress
69
Mechanisms of resistance against flucytosine? (very easy)
Loss of permease activity Loss of cytosine deaminase activity Decrease in the activity of uracil phosphoribosyl-transferase
70
Mechanisms of resistance against Echinocandins?
Point mutations in B1, 3-Glucan synthase Up regulated chitin synthesis (only in vitro)
71
Mechanisms of resistance to azoles?
Reduced intracellular accumulation - More efflux pumps Target site alteration Upregulation of target enzyme - overcomes competitive inhibition (only subtle) Alteration in sterol synthesis - cross resistance to polyenes
72
Facts about biofilms in hospitals?
Increasing use of prosthetic devices within the modern hospital (Kojic and Darouiche 2004) 95% of cases of urinary tract infections are associated with catheters (Darouiche et al 2001) Biofilms in comparison to planktonic cells are generally much more resistant to antibiotics and biocides
73
Vibrio cholerae (in exam all names of microorganisms can't be italic so underline them) think this will be in the exam has been a pandemic since?
1883
74
Vector of vibrio cholerae?
Plankton in the sea? This is affected by climate change from the warming of the water Ocean heat capacity measured rather than surface temperature as more reliable
75
Features of Vibrio cholerae?
``` Found in water Its a gram - rod Doesn't form spores It's motile Anyone is susceptible It's infectious, transmission via the fecal oral route Exposure from contaminated food or water Treatment through antibiotics and fluid replacement Been used as a biological weapon Has 2 chromosomes ```
76
How does temperature affect Vibrio cholerae?
Growth of it | Phytoplankton blooms
77
How does salinity affect Vibrio cholerae?
Growth of it | Expression of Vibrio cholerae toxin
78
How does sunlight affectVibrio cholerae?
Survival of it | phytoplankton blooms
79
How does pH affect Vibrio cholerae?
Growth of it
80
How does Fe(3+) concentration affect Vibrio cholerae?
Growth | Expression of toxin
81
How does chitin affect it?
Growth of V. cholerae | Attachment to exoskeletons
82
When suggesting further research in essay?
Say why and who this affects (businesses) Apply this sort of thinking in essay
83
When name micro-organism in essay what do you do?
Underline it
84
How can bacteria hide themselves?
Form a biofilm which protects them from the immune system Also allows them to replicate
85
What are microbiota?
The microorganisms that typically inhabit a specific environment
86
What is the microbiome?
The totality of microbes, their genomes and environmental interactions in a defined environment. e.g. the gut of a human, soil sample
87
What is dysbiosis?
Microbial imbalance on or within the body
88
2 phyla that dominate fecal matter?
Firmicutes and Bacteroidetes
89
What do microbes do?
Involved in immune system regulation remove toxins and carcinogens, crowd out pathogens (colonisation resistance), improve intestinal functions, gut-brain links in communication, as important to us as a liver- because of metabolites produced in gut. Considered as a vital organ
90
How does Naturally microbial succession occur?
from birth to later years (critical inoculation in infancy/birth).
91
Features of microbes and external organs?
, surface tissues (skin & mucous membranes and gut) are constantly exposed to environmental microorganisms and are readily colonized by diverse microbial (primarily bacterial) species
92
Whats the human microbiome project?
Highly parallel DNA sequencers combined with high-throughput mass spectrometers enable characterization of whole microbial communities including Genomes, proteins and metabolic products
93
What were the aims of the human microbiome project?
Determine whether individuals share a core human microbiome Can changes in the human microbiome be correlated with changes in human health?
94
What Significant advances were required in order to fully analyze the microbiome ?
Improved culture methods Perform genome sequencing in the absence of culture
95
Features of the normal healthy human microbiota?
There is the core part which majority of all humans have this set of genes Then there is a variable area which smaller subsets of humans have these genes
96
What's The most heavily colonized organ in the human body?
The GI tract, contains more than 70% of microbes in the body
97
Overview of gut microbiota?
Strict anaerobes outnumber facultative aerobes & aerobes Gut microbiota is dominated by just two phyla Bacteroidetes (e.g. Bacteroides) Firmicutes (e.g. Clostridium) Bacterial abundance increases as we progress from the stomach to the colon Colonization begins at birth, during passage through birth canal
98
Features of Neisseria meningitides?
It's a beta Proteobacteria Gram negative Carriage in the nasopharynx in 10-15% of the population Epidemics occur every 10-12 years Meningitidis belt in Africa where rates of infection can be 1 in 100 Classified by serogroup – reactivity to a bacterial polysaccharide capsule Can turn their capsule on and off There are 12 serogroups, 6 of which can cause epidemics Carriage is facilitated by downregulation or loss of capsule expression, as this sterically inhibits adherence and biofilm formation. However, survival in the bloodstream and in epithelial cells is enhanced by capsule expression
99
Features of Gram positive bacteria?
Example is Corynebacterium diphteriae Gram positive, immotile rod Colonises upper respiratory tract Route of infection: Airborne droplet Produces exotoxin Kills surrounding host cells Toxin spreads systemically Principally affects: Heart and Lungs Main cause of mortality Classic AB toxin - the main virulence factor (B is the binding factor)
100
Is there a link between obesity and intestinal microbiota?
Yes
101
What is H. pylori?
first formally recognized bacterial carcinogen ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. Susceptibility is multifactorial e.g. H. pylori virulence, environmental factors, genetic susceptibility of the host and status of host immune system. Difficult to eradiciate Gastric carcinoma development may be a result of host genetic, environmental and microbiological factors.
102
What's Faecalibacterium?
Anti-inflammatory commensal bacterium identified by gut microbiota analysis of chronic disease patients
103
Obesity-related shift in human microbiota?
A shift in the relative abundance of Bacteroidetes and Firmicutes has been observed in obese humans Furthermore, abundance of Bacteroidetes increased when dieting, with the change in abundance correlating with weight lost
104
Features of the GI tract that wipe out gram negative bacteria?
Gastic acid in stomach Paneth cells, Pancreatic enzymes, bile, intestinal enzymes, GALT, and peristalsis from the intestines Intestines also produce lysozyme and cryptins
105
Features of the genitourinary tract?
Low pH of urine and vaginal epithelia Urea and other toxic metabolic end products in urine Hypertonic nature of kidney medulla Flushing with urine and mucus
106
How do bacteria establish themselves?
Have adherence factors Normally multi factorial
107
Examples of secreted enzyme defences?
Leukocidins - Kill white blood cells including neutrophils and macrophages Produced by Stapylococcal and Streptococcal spp Coagulase - Causes fibrin clots to form in the blood of a host. Advantageous to the bacteria in evasion
108
Example of damaging chemicals bacteria release? (Exotoxins)
Neourotoxins - cause paralysis Enterotxins - cause sickness and diarrhoea Cytotoxins - cause cell death
109
The abundance of Faecalibacterium within the gastrointestinal tract is believed to influence Crohn’s disease because?
Faecalibacterium promotes the production of anti-inflammatory cytokines