lecture 4 Flashcards
Order: Vibrionales
General morphological and biochemical characteristics
family Vibrionaceae
* 4 genera including type genus Vibrio
* Gram negative straight/curved rod
* Facultative anaerobe
* Oxidase positive (most)
* Catalase positive
* Nitrate reductase positive
* Requirement for NaCl (salt) for growth
* G+C content 47%; 4-5 Mbp genome
* Two chromosomes
* Optimum growth 30-35 ˚C
* Motile (single polar flagella)
rising sea waters and global warming and increased temperatures are making them more prominent as people go to seaside on hot days and the exposure is increasing
aquatic organisms, that thrive in marine and brackish water >15 ˚C
Order: Vibrionales
Genera: Vibrio
> 50 species including
V. cholerae (waterborne infections)
V. parahaemolyticus (food (shellfish) infections)
V. vulnificus (wound infections)
Similarities with members of Enterobactericeae
- Gamma proteobacteria, Gram negative rods (sometimes curved)
- Facultative anaerobes / fermentative
- Genome size 4-5Mb, G+C content ~47%, genetically tractable
Differences with members of Enterobactericeae
- 2 chromosomes
- Single polar flagella (highly motile)
- Most oxidase positive
- Most live in aquatic habitats
Vibrio cholerae
- > 200 O antigen serogroups
*O1 and O139
Pan/epidemic cholera
Cholera toxin (CT) +
Waterborne /
person-to-person
*Non-O1, non-O139
Sporadic cases
Gastroenteritis (cholera-like?)
May be cholera toxin negative
Water/shellfish
regulation of gene producing cholera toxin may be different in the serovars which results in the severity of the diseases caused by different serovars
V. cholerae O1 impact
▪ acute secretory diarrhoeal disease
▪ endemic to 50 countries, and a public health
problem for the native population and for
travellers to these regions
▪ this ancient disease (5th century BC) remains a
considerable social and economic burden despite
nearly 150 years of study
▪ in midst of 7th pandemic; WHO estimates 3-5
million individuals affected by cholera per year;
current pandemic began in Indonesia in 1961 and
spread through Asia, Africa to Europe and Latin
America
Modern day cholera
Since mid-2021, the world is facing an acute upsurge of the 7th cholera pandemic characterized by the number, size and concurrence of multiple outbreaks, the spread to areas free of cholera for decades and alarming high mortality rates
current pandemic is being caused by el tor serovar
Figure – Incidence of cholera cases per 100,000 population reported to WHO from 1st January to 30 November 2022
V. cholerae infection
disease
* short incubation period (< 12 hours)
* early vomiting
* painless loss of copious amounts of watery
diarrhea (up to 1L per hour) known as
“rice-water stool”
-as well as causing huge amounts of water loss as diarrhoea cholera toxin induces mucas secretion in the intestines; the goblet cells that contain the mucin esentially coats the lining of the intestines; cholera toxin can induce an increased expression of mucin from the host
- severe and rapidly progressing
dehydration and hypovolemic shock - without treatment, severe cholera kills
about half of infected individuals
the vibrio cholerae that’s present in the diarrhoeal fluid is about 100 times more infectious than the same vibrio cholerae strain pulled out from a water resevoir; passage through the human intestine alters the gene expression in the bacteria and makes it more infectious
V. cholerae pathogenesis
very rapidly multiplying organism, much faster than E coli
Steps during infection:
extracellular pathogen that does not invade any cells and remains in the intestinal lumen
- in the lumen the pathogen needs to express cholera toxin and needs to express an adherance factor called TCP (toxin co-reguated pilus) which is a critical colonisation factor- this is a surface appendage that allows the cell to stick to the small intestines as that is the site of colonisation where the toxin is produced
cholera toxin is responsible for secretory diarrhoea- cholera toxin seeks out the receptor GM1 (a host glycoprotein) and gets taken up by the receptor into the epithelial cell
cholera toxin is known as an AB5 type toxin- it has 2 subunits an A and B subunit, 1 A and 5 B subunits; the B subunits recognise the GM1 receptor
and the A subunit activates the G protein in the cell which causes an increase in the expression adenylate cyclase which then increases the expression of the messenger cAMP which then alters and affects the ion absorption and secretion (the ions Cl- and Na+ in this case) this imbalance of ion concentration affects water distribution and causes water to be released, causing very watery diarrhoea)
- Ingestion and passage
through acidic stomach - Colonisation of small
intestine (distal region).;
organism remains
extracellular - Production of CT to induce
secretory diarrhoea and
mucin release - Exit from host in mucusassociated aggregates
Toxin co-regulated
pilus (TCP) – critical
colonisation factor
Cholera toxin (CT) –
responsible for
secretory diarrhoea
V. parahaemolyticus-
Enteritis (shellfish-borne infections)
very rapidly multiplying organism much faster than E coli
- Main clinical symptoms is watery
diarrhoea, often accompanied with
abdominal pain, nausea and vomiting - Typically a self-limiting illness, with rare
severe morbidity and mortality - Sporadic cases in UK (e.g. mitten crabs in
Thames (2003-2006); pathogenic strains
in coastal waters (2012)) - Most common pathogen in Japan & other
parts of Asia where raw seafood
consumption is high
V. parahaemolyticus
- Soft tissue infections / septicaemia
- entry via wounds or skin lesions, often
linked to injury due to handling
contaminated shellfish - symptoms of skin infection (swelling,
pain, erythema, bullae (blister), necrosis
and gangrene) - symptoms of septicaemia (fever,
hypotension, bullae, pain in lower
extremities, tachycardia, shock, multiorgan dysfunction) - infections may be life-threatening if there are other underlying conditions however most healthy people can clear the disease
V. parahaemolyticus virulence mechanisms
- hemolysins
(e.g. thermostable direct haemolysin
(TDH) and the thermostable direct related haemolysin variant, TRH); lysis of
red blood cells - Type 3 secretion system (T3SS)
Two systems in organism; T3SS1 causes
cytotoxicity (cell death) and T3SS2 is
associated with diarrhoea (enterotoxicity)
studies show that bile triggers expression
of T3SS2 genes – this provides a way for
the bacterium to know when to switch on
virulence factor production- the bacteria uses the host molecule, bile, to switch on its virulance factor
V. vulnificus: disease and routes of
infection
Disease:
1. Wound infection / septicaemia from exposure to organism in sea water
Can be fatal; rapidly spreading systemic disease → septicaemia
- Foodborne illnesses
* Raw oysters
* USA ~ 100 cases per year
* Responsible for >95% of all seafood associated deaths in USA
* Can be fatal (septicaemia)
* Healthy individuals rarely susceptible (liver damage, high serum iron)
V. vulnificus: virulence factors
- Hemolysin
Encoded by genes vvhA and vvhB; only secreted toxin; member of the cholesteroldependent cytolysin (CDC) family of pore-forming toxins; capable of dissolving red
blood cells - Proteases
e.g. VVP – an elastase that increases vascular permeability of host cells; other
functions in promoting clotting, which prevents effective host immune response
e.g. RtxA - MARTX toxin with multiple functions including interfering with actin
cytoskeleton rearrangements and promoting necrotic cell death - Capsule
Required for infection, ‘hides’ bacterium from the host immune response (e.g.
resistance to opsonization by complement and subsequent phagocytosis by
macrophages)- capsules help hide the bacterium from the host immune response so a key virulance factor to protect anything that needs to survive in the blood stream to allow for protection from the normal immune response
One more reference & next steps…..
Baker-Austin et al. (2018) Vibrio spp. infections. Nature Disease Primers 4:1-19.
https://www.nature.com/articles/s41572-018-0005-8 .
Summary of pathogenic Vibrio spp.
detail the information for
V. cholerae
V. para
V. vulnificus regarding their
-disease
-intestinal pathology
-infectious dose
-key virulence factors
-habitat /vehicle
disease
intestinal pathology
infectious dose
key virulence factors
habitat /vehicle
