COLLEGE OF HEALTH – YAMFO

Medical Microbiology 1 (BCOH201), for B.Sc.

Physician Assistants, Level 200

2021/2022 Academic Year, First Semester

Lecture Venue: Hon. Apraku Lartey’s Block, LH 1/2

Tutor: Benjamin Pulle Niriwa

Contacts’ Details: 0242015959, pullebenjamin@gmail.com
Office Hours: 8:00AM-5:00PM
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 OBJECTIVES AND ACTIVITIES
Lecture Objectives: Activities Time
Periods This Lecture Would Cover:
4th Week, Normal 1. What is Chlamydia 1. Tutor Gives Mon.,
21.02.2022 microbial The Species of Chlamydia Didactic 1:30PM
flora Lectures with to
2. Pathogenicity of Chlamydia example, 4:40PM
Pathogenesis of Chlamydia scenarios, and
demonstrates
3. How do these Pathogenesis
and Pathogenicities Benefit 2. Tutor ask
Chlamydia and the host? questions to
see if students
5. Conclusion & References understand

3. Students
participate by
discussing and
also asking
questions 2
 INTRODUCTION
Chlamydia species are normal mucosal flora found mostly in the
gut, urethra, and cervix.

Chlamydia is a genus of different species of pathogenic bacteria

that are obligate intracellular parasites with “Defective” cell
walls. They are however part of the mucosal normal flora.

Three main species of Chlamydia are known to be involved in

causing infections/diseases in man. They are:
 Chlamydia trachomatis,
 Chlamydia pneumoniae, and
 Chlamydia psittacci.
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 What Determine Their Pathogenicity?
They have varied virulence factors and their genomes
contribute for almost 10%. Their genes are conserved and are
used by them to survive but they have almost similar genomic
synteny.

Differences in their ability to cause infection and form disease,

(infection tropism) are determined by the constantly changing
nature of part of their genomes called “the plasticity zone.

It encodes so many different virulence factors such as;

“Membrane attack complex proteins, phospholipase, the type III
secretion system (T3SS), adhesions or cytotoxins” for the
microbe.
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 Major Outer membrane protein (MOMP)
This is made up of mostly of proteins within the outer
membrane which are pore-forming in nature. Their main actions
are to activate/trigger the targeted “killing” of microbes,
immune cells or host membranes.

It has Lipopolysaccharide (LPS) within the Major Outer

membrane protein (MOMP) that inhibits activities of phagocytes
and complement cascade from destroying the bacteria.

The LPS is able to do this because it is a protective barrier that

prevents or slows down entry of bile salts, antimicrobials and
other toxic substances that may damage the cell.

The MOMP forms porin (LPS) that allows glucose, other

monosaccharides and iron to enter the Chlamydial cells to
provide energy for it.
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 C. trachomatis Phospholipase
The plasticity zone (PZ) of Chlamydia encodes varied families
of phospholipase D (PLD) enzyme found in the different
Chlamydia species.

When there is any Chlamydia infection, there are transcriptions

of these enzymatic proteins; and there are also localization of
the respective PLD proteins with the “Reticulate bodies”.

The exact functions of phospholipase D (PLD) enzymes are not

clearly known, their mechanisms of actions are mostly by:
destroying their host cells,
changing the host’s “cell signaling to promote pathogen
uptake”,
releasing toxic substances to destroy the host’s cells, and
disrupting “cell membranes” of the host 6
 The Type III secretion system (T3SS)
Chlamydia trachomatis normally inoculates “toxins” and
“effector proteins” directly into host cells by injecting them
using the type III secretion system (T3SS).

The T3SS is a “multimeric protein complex” is also used by

most Gram-negative bacteria like E. coli, Pseudomonas
aeruginosa, Shigella spp., Vibrio cholera, and Yersinia pestis.

At the tip is a needle-like projection with a translocon which is a

pore through which the toxins and effector proteins are released

Toxins are normally injected into the host cells using the T3SS
which mostly result in the death of those cells. 7
 C. trachomatis Adhesions
C trachomatis attaches itself to mucosal surfaces, by triggering
production of adhesion molecules (adhesion molecule-1).

The EBs adhere or bind themselves reversibly to the host cells

at the initial stages of the infection and later irreversibly by,
using the adhesion molecules.

The bacterium “adhersins OmcB” and MOMP interact by

recognizing and binding themselves to “heparan sulfate
proteoglycans” (HSPG) at the host’s “cell membranes”.

The next attachment of the EBs is facilitated by the

“Polymorphic membrane proteins (Pmps)” which are 9 in
number.
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 Chlamydia trachomatis Cytotoxins
• The genome of C. trachomatis has some genes that are mostly
involved in the encoding of proteins that look similar to that of
“large clostridial cytotoxins”.

• Chlamydia species make “a replication-independent cytotoxic

activity” to produce epithelial cells morphologically and
cytoskeletally different, that cannot be differentiated from the ones
produced by the mediation of Clostridial’s toxin B

• Based on antigenic classification or identification, Chlamydia

trachomatis are grouped as fifteen (15) different serotypes;
identified by the letters A-K, L1-L3, and MoPn.

• In the plasticity zone of strain MoPn, there are three (3) Open
Reading Frames “ORFs” (TC0437-0439) that always encode
proteins similar to large cytotoxins (LCTs) A and B that C. difficile
produces. 9
 Chlamydia Species Pathogenesis
C. trachomatis infects non-ciliated columnar epithelial cells. It
normally stimulates infiltration of polymorphonuclear cells and
lymphocytes.

The clinical manifestations result from destruction of the cells

and the host inflammatory response.

For C. psittacci, respiratory tract is the main portal of entry

when they are inhaled from infected birds or their droppings.

They go first to the lungs before entering the blood stream to

be transported to the liver and spleen. The bacteria replicate at
these sites to form focal areas of necrosis.
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Figure 1: Chlamydia Biphasic Life Cycle
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Fig 2: Developmental Cycle, Chlamydia

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 Chlamydia Developmental Life Cycle
The unique developmental life cycle of Chlamydia itself is a
source of pathogenicity!

Before Chlamydia infection could occur, the infectious but

inactive form called the elementary bodies (EBs) has to find its
way into the host.

EBs, are normally found on mucosal surfaces in the semen of

men, vaginal secretions/fluids. So, when lovers are making love
or having sex they transmit them to the opposite sex.

They transform into the noninfectious form called the

“Reticulate Body” and that time they cannot be detected or
identified by phagocytes of the host’s immune system.
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 Chlamydia Developmental Life Cycle
Eukaryotic cell binding protein: Host response: damage to
specific tissues.

Chlamydiae attach to, and enter, eukaryotic epithelial cells of

mucosal surfaces and grow within host cell membrane-bound
vacuoles that do not fuse with lysosomes.

The biphasic life cycle makes it easy for them to continually

change from one form to another; ‘EBs’ to ‘RBs’ as a defense
mechanism for survival.

The persistent survival of “Obligate intracellular” Chlamydia

species inside the host is made possible because of its “biphasic
life cycle”.
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 Chlamydia Developmental Life Cycle
How Chlamydia Pathogenesis Benefit It and the Host
Chlamydia trachomatis is able to hide from immune phagocytic
cells because of the ability to form endospores at the reticulate
bodies’ stage.

Endospores protect the bacterium from being destroyed by

phagocytes, antimicrobials, starvation, normal heat even at
boiling temperature, UV light, or interferon gamma “IFN-γ”.

This IFN-γ encoded by the genetic materials of the plasticity

zone (PZ) normally help to activate the innate immune system
of the host against infections.
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 How Chlamydia Pathogenesis Benefit
It and the Host
Chlamydia-infested vacuole divert lipids to itself rather than to
another compartment of the host cell. They have higher degree
of mutation and their cells can synthesize DNA, RNA and protein

It has an autophagic that enables the host cell to recycle

intracellular components to provide protection against
pathogens.

Chlamydia has specific CD4 T-helper cell one (Th1)-interferon-

γ-producing cells that protect the host from other infections and
diseases. 16
 Chlamydia Developmental Life Cycle

The
endospore is
normally
formed at
the RB stage
of the
Chlamydia
life cycle

Figure 3: Picture of An Endospore

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 Chlamydia Virulent Factors (Cont.).
The unique cell wall of Chlamydia trachomatis is thought to be
one of its virulence factors, as it inhibits phagolysosome fusion
in phagocytes.

The cell wall contains an outer lipopolysaccharide membrane

but lacks peptidoglycan. It rather contains cysteine-rich proteins
that are likely the functional equivalent of peptidoglycan.

This unique cell wall structure, allows for intracellular division

and extracellular survival.

They are able to escape the harsh environments created by

antimicrobial agents or immune cells. Their ability to persist is
because at such conditions, they are still “viable” but do not
develop or replicate.
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 Chlamydia Virulent Factors (Cont.).
Chlamydia infection female mostly include: dysuria, abnormal
discharges seen in the vagina, bleeding abnormally during
menstruation, bleeding postcoitally, and pains in the lower abdomen.

When Chlamydia trachomatis infection is not treated in some of the

women, it uses the endometrium’s epithelial areas to travel into the
fallopian tubes and cause “pelvic inflammatory disease (PID),
infertility, ectopic pregnancy or pelvic pain” that keeps recurring.

In terms of percentage, more than 50% of Chlamydia trachomatis

infection in women leads to infertility or ectopic pregnancy, but,
there did not experience anything that shows that they were infected
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 Chlamydia Virulent Factors (Cont.).
Chlamydia cause eyes infections or
trachoma and sexually transmitted
infections in humans.

In women it causes “cervicitis” and

also causes “non-gonococcal urethritis
in men”.

Figure 3: It causes “endocervical discharge” in

Keratoconjunctivitis/Trachoma
women and “hypertrophic cervical
ectopy” resulting in ectopic pregnancy
as birth problem for women
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ThANK YOU!

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 Some References
• Betts-Hampikian, H. J. (2010). The Chlamydial Type III Secretion Mechanism: Revealing Cracks In a
Tough Nut. Front Microbiol , 1:114. Doi: 10.3389/fmicb.2010.00114.
• Brunham a., R. C. (2013). Chlamydia trachomatis Control Requires a Vaccine. Author’s Manuscript,
Vaccine , 31(15): 1892–1897. Doi: 10.1016/j.vaccine.2013.01.024.
• Elwell, C. M. (2016). Chlamydia Cell Biology and Pathogenesis. Nat Rev Microbiol , 14(6): 385–400. Doi:
10.1038/nrmicro.2016.30.
• Fechtner, T. S. (2013). Characterization of the Interaction Between the Chlamydial Adhesin Omcb and
the Human Host Cells. J Bacteriol , 195: 5323-5333. .
• Hotinger, J. A. (2020). Antibodies Inhibiting the Type III Secretion System of Gram-Negative Pathogenic
Bacteria. Antibodies , 9:35. Doi: 10.3390/antib9030035.
• Keb, G. &. (2020). An Ancient Molecular Arms Race: Chlamydia vs. Membrane Attack Complex/Perforin
(MACPF) Domain Proteins. Front. Immunol , 11:1490. Doi: 10.3389/fimmu.2020.01490.
• Kelly, K. A. (2001). Chlamydia trachomatis Infection Induces Mucosal Addressin Cell Adhesion
Molecule-1 and Vascular Cell Adhesion Molecule-1, Providing An Immunologic Link Between the
Fallopian Tube and Other Mucosal Tissues. J Infect Dis , 184(7): 885–891. Doi: 10.1086/323341.
• Lara-Tejero, M. &. (2019). The Injectisome, A Complex Nanomachine for Protein Injection Into
Mammalian Cells. EcoSal Plus , 8: 245-259.
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