Lecture 3 Flashcards

You may prefer our related Brainscape-certified flashcards:
1
Q

Order: Enterobacterales
General morphological and biochemical characteristics

A
  • 29 genera including type genus Escherichia, as
    well as other genera e.g. Salmonella, Klebsiella,
    Enterobacter
  • Optimum temperature 37 °C- suggests they reside in mamalian hosts
  • Gram-negative, non-spore forming rods
  • Facultative anaerobes- can grow in both oxygen and the absence of oxygen
  • Catalase positive
  • Oxidase negative
  • Nitrate reductase positive
  • Motile, via peritrichous flagella (a few exceptions)
  • DNA genome characteristics: G+C content 38-60%; genome size ~5 M bases- large genome for bacteria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Enterobactericeae: common aspects

A
  • Habitats: gastrointestinal tract of hosts including humans, animals and insects
  • Widespread contamination of environment: sewage, soil, water, plants, food- found in plants as we use animal faeces for fertalising
  • Routes of infection: oral, via wounds, urinary tract, respiratory tract
  • Disease: diarrhoea, sepsis, urinary tract, CNS and brain
  • Among the most pathogenic and most often
    encountered organisms…….

Food-borne illness
alone affects 1
million people
each year in the
UK

Half of all women experience
a UTI in their lifetime; ~70% of
UTIs are caused by E. coli
- E.coli is a dominant aerobic organism in the gut but represents a small proportion of the microbiome in the gut

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Classification of Salmonella species is complex
why?

A
  • 2 species
    7 subspecies
    >2,600 serovars
  • Some serovars are
    host-restricted e.g.
    Typhi (human);.
    Abortusovis
    (sheep)
  • Most serovars
    infect a wide range
    of hosts e.g.
    Typhimurium
  • serovars are like a group; they are being classified on their surface antigens
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

how were species originally defined?

A

Species and subspecies were originally defined by DNA-DNA hybridisation, confirmed by MLEE and MLST and are currently differentiated by biochemistry and serology

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what is the difference between typhoidal and non-typhoidal salmonella?

A

The split in typhoidal and non-typhoidal is based on the disease syndrome. Typhoid and paratyphoid fever is prolonged, whilst extra-intestinal infection is usually acute and metastatic. Gastroenteritis is characterised by diarrhoea.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

how are serovars differentiated?

A

Differentiation of serovars is by agglutination with specific antisera against LPS (O), two phases of flagella (H1 and H2). There are 46 0 antigen, 85 H antigen and 1 capsule antigen (Vi/k) antigen which have been described in about 1. 500 combinations within subspecies 1.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Genus Salmonella:
general characteristics

A
  • Non-lactose fermenter (E. coli ferments lactose but Shigella does not)
  • Indole test negative (E. coli positive; Shigella variable)
  • Various selective medias can distinguish
    Salmonella from E. coli / Shigella by:
  • H2S production
  • Acid production during
    carbohydrate fermentation
    e.g. XLD media, SS media

on XLD media
E. coli – yellow
Salmonella – black
Shigella - red

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Typhoidal Salmonella : impact & disease

A

Typhoid fever (S. Typhi)
~ 15 million new cases each year, with
about 1% deaths

1st phase:
slow fever, rose spots, mild, bacteremia

2nd phase:
organism reaches gallbladder, formation of
ulcers, haemorrhage, death (20%)

Typhoid state “muttering delirium” or “coma
vigil” (picking at bedclothes and imaginary
objects)- has neurological impact

Enteric fever (S. Paratyphi)
→ similar to typhoid fever but less severe; rare

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Non-typhoid Salmonella (NTS): impact

A

-often a foodborn illness

  • Global burden ~94 million cases (155,000 deaths) each year, of which
    about 80 million were estimated as foodborne origin
  • UK data: 8-9,000 confirmed cases per year
  • Predominant serovars:
    Salmonella Enteritidis
    Salmonella Typhimurium
    Salmonella Heidelberg
    Salmonella Newport
  • NTS causes self-limiting enteritis
    in healthy individuals- as most individuals’ immune systems can contain the bacteria
  • Can be invasive (iNTS) in regions
    with immunocompromised /
    malnourished individuals e.g. in
    sub-Saharan Africa
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

NT Salmonella: infection and
pathogenesis

A

Despite differences in disease outcome, all Salmonella must cross epithelial barrier to colonise the host
* cross epithelium via phagocytic cells (M cells, DCs) or direct uptake; can g through a vacuole
* targets macrophages, or re-invades epithelial cells from basolateral side
* may evade killing by inducing macrophage apoptosis / manipulate for bacterial replication
* severe disease results from systemic spread and bacteraemia

However a healthy individuals immune system can clear this disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Main Salmonella virulence factors:
Type 3 secretion systems (T3SSs) – encoded on Salmonella
pathogenicity island (SPI)

A

T3SS = molecular
‘syringe’ that transfers
proteins (effectors)
from bacterial
cytoplasm to host cell

T3SS attaches to a host cell and injects effectors into the cell

SPI1 – encodes genes
necessary for invasion
of intestinal epithelial
cells and induction of
intestinal secretory and
inflammatory responses

SPI2 – encodes genes
essential for intracellular replication and
necessary for
establishment of
systemic infection
beyond the intestinal
epithelium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Vehicles of NTS Salmonella infection (UK)

A
  • Route: faecal-oral transmission
  • Predominantly poultry and poultry products but many foods have been
    associated with infection
  • UK: pre-1980s Eggs! after 1980s a vaccine was created to prevent the bacteria
  • UK: meat, milk,
    sausages and even
    chocolate!

-5/5/22 – 101 cases
linked to ‘Kinder’
outbreak, most in
children < 5 years old

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Genus: Escherichia

A
  • Escherichia genus – E. coli first isolated 1919, Theodor Escherich
  • Five species: E. albertii, E. coli, E. fergusonii, E. hermannii, E. vulneris
  • E. coli colonises mammalian GI tract a few hours after birth and maintains
    regular presence over lifetime
  • Of >700 different serotypes (O,H,K), most are harmless
  • Pathogenic strains are assigned to ‘pathotypes’ based on the type of
  • when refering to E.coli we differetiate via their pathotypes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Pathotype vs serotype?

A

Pathotype and serotype are both terms used to classify microorganisms, but they refer to different aspects of microbial characteristics:

Pathotype:
Definition: Refers to a classification based on the disease-causing ability or the pathogenic traits of a microorganism. Pathotypes are strains or groups of organisms that cause similar types of infections or exhibit similar virulence factors.
Focus: Pathogenic behavior or the ability to cause disease.
Example: Different strains of Escherichia coli can be classified into pathotypes based on the diseases they cause, such as:
Enteropathogenic E. coli (EPEC): Causes diarrhea, especially in infants.
Enterohemorrhagic E. coli (EHEC): Causes severe intestinal infections and can lead to kidney damage.

Serotype:
Definition: A classification based on the antigenic properties of an organism, particularly the recognition of different surface structures (such as proteins, polysaccharides, or lipopolysaccharides) by antibodies.
Focus: The immune response and antigenic variation, i.e., how the immune system recognizes different strains.
Example: Different serotypes of bacteria or viruses are distinguished by their surface antigens, such as:
Salmonella enterica has over 2,500 serotypes (e.g., Salmonella Typhi, Salmonella Enteritidis).
Dengue virus has four major serotypes (DENV-1, DENV-2, DENV-3, DENV-4).

Summary:
Pathotype refers to the pathogenic behavior and ability to cause disease.
Serotype refers to the antigenic properties recognized by the immune system.
Both can be used to differentiate between strains of the same species, but they focus on different aspects—disease-causing traits vs. antigenic characteristics.

“Serotype refers to the antigenic properties recognized by the immune system” means that different serotypes of a microorganism (such as a bacterium or virus) are classified based on their surface antigens, which are the molecules that the immune system detects and responds to.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

E. coli disease pathotypes- intestinal infections

A
  • Enteroaggregative
    E. coli-(EAEC)

-Enterotoxigenic
E. coli (ETEC)

-Enteroinvasive
E. coli (EIEC)

-Shiga toxin-producing
E. coli (STEC) or
Enterohaemorrhagic
E. coli (EHEC) (Attaching and effacing
E. coli)- no treatment for them

-Enteropathogenic
E. coli (EPEC) (Attaching and effacing
E. coli)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

E. coli disease pathotypes- extra-intestinal infections
(ExPEC)

A

uropathogenic
E. coli (UPEC)- (UTIs)

meningitis-associated
E. coli (MNEC)- (Meningitis)

septicaemic E. coli (SEPEC)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Urinary tract infections (UTIs)

A
  • 50% of women get a UTI in their lifetime
  • 75% of UTIs are caused by uropathogenic E. coli
    (UPEC)
  • UTI infection: 14x more common in
    females (shorter urethra)
  • In the pre-antibiotic era, 15% of UTI
    cases were fatal
  • Types of UTI include:
    asymptomatic bacteriuria (1% normally, 20% elderly)
    cystitis (bladder infection)
    pyelonephritis (upper ureter infection, kidney infection)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Mechanism of UPEC infection

A

Intestine of healthy
individuals contain UPEC

Periurethral contamination
with UPEC can occur after
a bowel movement or
during sexual intercourse

UPEC produce P-fimbriae which
recognises a blood
group antigen (Dgalactose-D-galactose)
found in 99% of people

19
Q

Meningitis-associated E. coli (MNEC)

A
  • Affects 1 in every 2,000 – 4,000 infants
  • Major cause of CNS infections in infants < 1 month old
  • Primary bloodstream infection with secondary distribution to the central
    nervous system (CNS) is the mechanistic basis of infection
  • 80% of E. coli strains involved synthesize K-1 capsular antigens
  • K-1 antigen is a major virulence factor (a homopolymer of sialic acid)
  • K-1 strains are common in the GI tract of pregnant women and newborns
20
Q

Intestinal pathogenic E. coli (InPEC)

A
  • common cause of gastrointestinal infections (1 in 5 people affected each
    year in UK)
  • transmitted by infected food and water (or via person-to-person)
  • symptoms vary depending on pathotype:

mild watery diarrhoea…….typically ETEC
dysentery……………………typically EIEC
severe bloody diarrhoea…………….typically EHEC
persistent diarrhoea…….typically EPEC, EAggEC
vomiting, abdominal pain, fever……..…all?
haemolytic uraemic syndrome (HUS)…only EHEC

  • Different pathotypes cause very different illnesses
21
Q

Intestinal pathogenic E. coli
-ETEC

A

Watery diarrhoea

High infectious dose
10^6 organisms

Site of damage - small
intestine; extracellular

Toxins: LT and ST

Colonisation factor
e.g. fimbriae

Treatment:
Self-limiting; oral
rehydration; antibiotics (e.g.
fluoroquinolones)

22
Q

Intestinal pathogenic E. coli- EIEC

A

Dysentery, bloody
diarrhoea

High infectious dose 10^6
-10^10 organisms

Site of damage – colon;
intracellular- bloody diarrhoea is usually as a result of damage to the colon

Toxins: none

Colonisation factor
e.g. pINV (T3SS)

Treatment:
Oral rehydration; Antibiotics
(e.g. azithromycin)

23
Q

Intestinal pathogenic E. coli- EAggEC

A

Diarrhoea (persistent)

High infectious dose 10^10
organisms

Site of damage – colon;
extracellular

Toxins: SPATEs
(proteases), enterotoxins

Colonisation factor
e.g. fimbrial & afimbrial
adhesins

Treatment:
Self-limiting; oral
rehydration; antibiotics (e.g.
rarely)

24
Q

Intestinal pathogenic
E. coli- EPEC

A

Diarrhoea

High infectious dose
10^8-10^10 organisms

Site of damage - colon;
extracellular
Toxins: proteases
Colonisation factor
e.g. A/E lesion (LEE
pathogenicity island)
Treatment:
Self-limiting, oral
rehydration; antibiotics
(rarely)

25
Q

Intestinal pathogenic
E. coli- EHEC/STEC

A

Bloody diarrhoea, kidney
disease

Low infectious dose
50-500 organisms

Site of damage - colon;
extracellular

Toxins: Shiga toxin (Stx)

Colonisation factor
e.g. A/E lesion (LEE
pathogenicity island)

Treatment:
None at present

LEE contains genes coding for
type 3 secretion system
(T3SS)

T3SS enables bacterium to
export proteins directly into
host cell

EPEC/EHEC export their own
receptor called Tir, which
interacts with outer
membrane protein called
intimin, to form an A/E lesion

26
Q

What differences exist between E. coli
pathotypes ?

A

Different pathotypes of Escherichia coli (E. coli) are classified based on their disease-causing mechanisms, virulence factors, and the specific diseases they cause. Each pathotype of E. coli has distinct features that determine how it interacts with the host and the type of illness it induces.

Major E. coli Pathotypes and Their Differences:

*Enteropathogenic E. coli (EPEC):

Mechanism of Pathogenesis: EPEC causes disease by attaching to intestinal epithelial cells and causing attaching and effacing (A/E) lesions, which destroy the microvilli of the intestinal lining.
Virulence Factors: EPEC has a type III secretion system that injects proteins into host cells, leading to cytoskeletal rearrangements and loss of absorptive surface area.
Disease: EPEC is a major cause of diarrhea, particularly in infants in developing countries, leading to watery diarrhea.

*Enterohemorrhagic E. coli (EHEC):

Mechanism of Pathogenesis: EHEC produces Shiga toxins (Stx1 and Stx2), which cause damage to blood vessels in the intestines, kidneys, and other organs.

Virulence Factors: Shiga toxin, type III secretion system, A/E lesions.
Disease: EHEC is associated with bloody diarrhea and can cause severe complications like hemolytic uremic syndrome (HUS), which can lead to kidney failure. The most notorious strain is E. coli O157.

*Enterotoxigenic E. coli (ETEC):

Mechanism of Pathogenesis: ETEC causes disease by producing heat-labile (LT) and/or heat-stable (ST) enterotoxins, which stimulate secretion of electrolytes and water into the intestinal lumen.
Virulence Factors: LT and ST toxins, colonization factors (CFs) that allow attachment to the intestinal mucosa.
Disease: ETEC is a leading cause of traveler’s diarrhea and infantile diarrhea in developing countries, resulting in profuse watery diarrhea.

*Enteroinvasive E. coli (EIEC):

Mechanism of Pathogenesis: EIEC invades and destroys epithelial cells in the colon, similar to Shigella, causing inflammation and tissue destruction.
Virulence Factors: Invasive plasmid antigens (Ipas) that enable cell invasion.
Disease: EIEC causes dysentery-like illness characterized by bloody diarrhea, fever, and abdominal cramps.
Enteroaggregative E. coli (EAEC):

Mechanism of Pathogenesis: EAEC adheres to the intestinal mucosa in a “stacked-brick” formation, forming a biofilm that interferes with nutrient absorption.
Virulence Factors: Aggregative adherence fimbriae (AAF), toxins like the EAST1 enterotoxin.
Disease: EAEC is associated with persistent diarrhea, especially in children and immunocompromised individuals, and sometimes chronic diarrhea.

*Diffusely Adherent E. coli (DAEC):

Mechanism of Pathogenesis: DAEC adheres diffusely to intestinal epithelial cells, leading to inflammation and mild diarrhea.
Virulence Factors: Diffusely adhering fimbriae (DAF), toxins.
Disease: DAEC is linked to mild diarrhea in children and has a weaker association with disease compared to other pathotypes.

Summary of Differences:
Mechanisms of pathogenesis: Pathotypes differ in how they attach, invade, or release toxins in the host.
Virulence factors: Each pathotype has unique sets of toxins, adhesins, or invasion systems.
Diseases caused: Ranges from watery diarrhea (ETEC, EPEC) to bloody diarrhea (EHEC, EIEC) and even severe systemic complications like hemolytic uremic syndrome (EHEC).

These differences in pathogenesis and virulence factors lead to the variety of gastrointestinal diseases caused by E. coli pathotypes.

27
Q

E. coli colonisation loci in the human host- ExPEC

A

Respiratory tract
Gallbladder
Skin and soft tissue

28
Q

E. coli colonisation loci in the human host- UPEC

A

Kidney
prostate
Bloodstream
bladder and urethra

29
Q

E. coli colonisation loci in the human host - Large intestine loci

A

Large intestine EHEC EIEC EAEC - AlEC (in Crohn’s disease and possibly colorectal cancer), possibly DAEC (associated with ulcerative colitis)

30
Q

E. coli colonisation loci in the human host - small intestine loci

A

Small intestine - EPEC | ETEC | DAEC | EAEC AIEC in Crohn’s disease (distal part ileum)

31
Q

Genus Shigella

A

Genetic features
* 4 Shigella species (based on serological typing)

A: S. dysenteriae – most severe, (ancient) cause of epidemics

B: S. flexneri – most frequent, 60% cases in developed world- common disease causing

C: S. boydii – confined to Indian sub-continent

D: S. sonnei – mildest infection, developed world (main species)- common disease causing

Phylogenetic typing (16S rRNA) now shows
that Shigella spp. and E. coli are one
species but the clinical community has kept
the original designation

shigella is a human only pathogen

32
Q

Shigella spp. disease impact

A
  • > 190 million cases of shigellosis annually worldwide, causing at least
    70,000 deaths
  • Current global epidemiological burden for shigellosis is
    attributed to S. flexneri and S. sonnei
  • Shigella is able to induce sustained transmissions in close
    contact communities
    e.g. Orthodox Jewish communities in UK
    e.g. Men who have sex with men (MSM community)

Treatment:
* Shigella spp. are becoming increasingly resistant to antibiotics
* Recommended first-line treatment for shigellosis is fluoroquinolones, such as
ciprofloxacin

33
Q

Shigella transmission and disease

A
  • Shigella is a human-only pathogen
  • Transmits by faecal-oral route and person-person
    spread
  • Shigellosis (dysentery) – clinical presentation of
    Shigella infection
    ➢ aggressive watery or mucoid/bloody
    diarrhoea, fever and stomach cramps
    ➢ begins 1-2 days after ingestion of organism
    and in immunocompetent individuals will
    resolve in 5-7 days;
    ➢ affects mostly children < 5 years
  • Low infectious dose (10-100 organisms)
34
Q

Shigella pathogenesis

A
  • Clinical disease reflects Shigella invasion and destruction of the large intestine
    epithelium

➢ Shigella is invasive so crosses epithelium
via M cells and induces
uptake by macrophages
➢ Shigella kills macrophages
& escapes to reach the
epithelium’s basolateral
surface
➢ Back inside the epithelial
cell, the bacterium induces
lysis of the phagosome in
which they are contained,
and begins to disseminate
intracellularly

shigella bacteria use host cell actin to travel inside the cell

35
Q

Shigella virulence factors

A

Plasmid-borne factors (pINV)
* Entry region – codes for type 3 secretion
system (T3SS), which allows the
bacterium to inject proteins directly into
the host cell
* T3SS is pivotal to infection
-when inside the cell the shigella is able to use the host cells actin to travel around inside the cell

Chromosomal factors
SHI-1 – enterotoxins (SigA, Pic, Set1A,1bB
SHI-2 – siderophores (IucA-D, IutA)
SHI-3 – siderophores (IucA-D, IutA)
SHI-O – serotype conversion/O-antigen
Stx-phage p27 – shiga toxin

36
Q

Order: Enterobacterales
General morphological and biochemical characteristics

A

emended family Enterobacteriaceae
* 29 genera including type genus Escherichia
* Optimum temperature 37 °C
* Gram-negative, non-spore forming rods
* Facultative anaerobes
* Catalase positive
* Oxidase negative
* Nitrate reductase positive
* G+C content 38-60% genome size ~5 Mbp
* Motile, via peritrichous flagella (a few exceptions)

family Yersiniaceae
* 7 genera including type genus Yersinia
* Optimum temperature 28-29°C
* Some lack nitrate reductase
* G+C content ~47%; genome size 4.6 Mbp
* Non-motile at 37°C (with all but Y. pestis motile by peritrichous flagella below 30°C)

37
Q

Genera: Yersinia

A
  • 17 Yersinia species
    → 3 species are pathogenic to humans or animals:

-food- and waterborne transmission routes
Y. enterocolitica
self-limiting gastroenteritis
Y. pseudotuberculosis
self-limiting gastroenteritis usually without diarrhoea
rare but more likely to become systemic

-flea-based transmission
Y. pestis
pneumonic and bubonic plague

38
Q

Y. enterocolitica / pseudotuberculosis:
disease and impact

A

➢ ~100 cases/year foodborne infection worldwide, low mortality rate
➢ self-limiting acute gastroenteritis and mesenteric lymphadenitis that mimics
acute appendicitis
➢ symptoms: fever, vomiting, abdominal pain (localised to right hand side),
diarrhoea
➢ most common in individuals < 7 years old
➢ rare systemic or rheumatologically (joint) complications

Treatment
➢ Usually self-limiting – supportive care only
➢ Antibiotics on occasion of sepsis (e.g. fluoroquinolones)

39
Q

Y. pestis: impact

A
  • Causative agent of plague
  • Huge impact on society since 6th century
  • 100s of millions have died
  • Historically caused major pandemics

e.g. Black Death (1347-1352)
* originated in Asia and spread to the Crimea, then Europe and Russia
* a quarter of Europe’s population were killed (25 million)
Y. pestis: impact
* Causative agent of plague
* Huge impact on society since 6th century
* 100s of millions have died
* Historically caused major pandemics
30
* Today
WHO reports 1-2,000 cases per year globally (8-10% mortality)

40
Q

Plague exists as a disease of wild rodents
and can be transmitted to humans by fleas

A
41
Q

Clinical aspects of plague

A

Bubonic plague
Y. pestis transported to regional lymph nodes (LN) but
survives and grows in normal unactivated
macrophages
-Massive proliferation in LN causes inflammatory
response (bubo)

; death about 60% and so disease may stop thus resulting in

Septicaemic plague (black death)
Y. pestis escapes LN and spreads to bloodstream,
lysis of bacteria releases LPS, causing septic shock

;Death virtually 100% so disease progression resulting in

Pneumonic plague
Y. pestis invades lung macrophages, organism is
now transmitted in aerosols (highly contagious)

42
Q

Yersinia use M cells to enter the host but remain
extracellular on macrophages

A
  • Despite different routes of host entry,
    all pathogenic Yersinia cross the
    epithelial barrier
  • Yersinia does this via M (microfold)
    cells -specialised epithelial cells of
    mucosal-associated lymphoid tissue
    (MALT)
  • Yersinia quickly traffics to lymph
    nodes or tissues, and establishes
  • Yersinia spreads systematically by
    accessing the bloodstream and
    colonising deep tissue sites, such as
    liver and spleen

In contrast to Salmonella, Yersinia
remain extracellular in macrophages

43
Q

Yersinia virulence factors

A

Type 3
secretion
system (T3SS)
is found in all
pathogenic
Yersinia

Y. pestis has acquired additional plasmid DNA that encodes for factors that enable colonization
and transmission via the flea vector and survival in blood but has lost motility and cell adhesive
properties to enable colonisation of mammalian host.

44
Q

References for further reading

A

Octavia and Lan (2014) The Family Enterobacteriaceae. In: The Prokaryotes – gammaproteobacteria,
Chapter 13, 226-283. Editors: E. Rosenberg et al. Sprineger-Verlag, Berlin Heidelberg.

Geurtsen et al., (2022) Genomics and pathotypes of the many faces of Escherichia coli. FEMS Microbiology
Reviews: 46: https://doi.org/10.1093/femsre/fuac031

Eng et al., (2015) Salmonella: A review on pathogenesis, epidemiology and antibiotic resistance, Frontiers in
Life Science, 8:3, 284-293,
https://www.tandfonline.com/doi/full/10.1080/21553769.2015.1051243

Davis (2018) All Yersinia are not created equal: phenotypic adaptation to distinct niches within mammalian
tissues. Front. Cell. Infect. Microbiol. | https://doi.org/10.3389/fcimb.2018.00261

Demeure et al. (2019)Yersinia pestis and plague: an updated view on evolution, virulence determinants,
immune subversion, vaccination, and diagnostics Genes & Immunity volume 20, pages357–370.
https://www.nature.com/articles/s41435-019-0065-0

Baker and The (2018) Recent insights into Shigella: a major contributor to the global diarrhoeal disease
burden. Curr. Opin. Infect. Dis 31:449-454 doi: 10.1097/QCO.0000000000000475

Mattock and Blocker (2017) How do the virulence factors of Shigella work together to cause disease?
Frontiers in Cellular and Infection Microbiology 7 article 64. https://pubmed.ncbi.nlm.nih.gov/28393050/