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Key concepts
§ Infection
§ Sources of infection
§ Method of transmission of infection,

§ Factors predisposing to microbial pathogenicity,

§ Types of infectious diseases
§ Identification of virulence factors
§ Host and bacterial factors
§ Virulence regulation, toxins, other toxic factors
§ Opportunistic bacteria

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INTRODUCTION TO BACTERIAL PATHOGENESIS

The process of causing disease is termed as Pathogenesis. Pathogenesis is a multi-factorial

process which depends on the immune status of the host, the nature of the species or strain
(virulence factors) and the number of organisms in the initial exposure.

A limited number of bacterial species are responsible for the majority of infectious diseases in
healthy individuals. Due to the success of vaccination, antibiotics, and effective public health
measures, until recently, epidemics were felt to be a thing of the past.
Due to the development of antibiotic resistant organisms, this situation is changing rapidly.

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INTRODUCTION TO BACTERIAL PATHOGENESIS

§ Pathogenicity is the capacity to initiate disease. It requires the attributes of

transmissibility or communicability from one host or reservoir to a fresh host,
survival in the new host, infectivity or the ability to breach the new host’s defenses,
and virulence, a variable that is multifactorial and denotes the capacity of a
pathogen to harm the host.

§ Virulence in the clinical sense is a manifestation of a complex bacterial–host

relationship in which the capacity of the organism to cause disease is considered in
relation to the resistance of the host.

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TYPES OF BACTERIAL PATHOGENS
§ Bacterial pathogens can be classified into two broad groups, primary and opportunistic
pathogens.
§ Primary pathogens are capable of establishing infection and causing disease in previously
healthy individuals with intact immunological defenses. However, these bacteria may more
readily cause disease in individuals with impaired defenses.

§ Opportunistic pathogens rarely cause disease in individuals’ with intact immunological and
anatomical defenses. Only when such defenses are impaired or compromised, as a result of
congenital or acquired disease or by the use of immunosuppressive therapy or surgical
techniques, are these bacteria able to cause disease.
§ Many opportunistic pathogens, e.g. coagulase negative staphylococci and Escherichia coli,
are part of the normal human flora and are carried on the skin or mucosal surfaces where
they cause no harm and may actually have beneficial effects, by preventing colonization by
other potential pathogens. However, introduction of these organisms into anatomical sites
in which they are not normally found, or removal of competing bacteria by the use of
broad-spectrum antibiotics, may allow their localized multiplication and subsequent
development of disease.
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KOCH’S POSTULATES (MODIFIED)

§ Koch forwarded four criteria designed to establish a causal relationship between a

causative microbe and a disease. The postulates were formulated by Robert Koch and
Friedrich Loeffler in 1884 and refined and published by Koch in 1890.
§ Koch applied the postulates to establish the etiology of anthrax and tuberculosis, and
now have been generalized to other diseases.

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KOCH’S POSTULATES (MODIFIED)
1. The organism must always be found in humans with the infectious disease but not found
in healthy ones.
2. The organism must be isolated from humans with the infectious disease and grown in
pure culture.
3. The organism isolated in pure culture must initiate disease when reinoculated into
susceptible animals.
4. The organism should be re-isolated from the experimentally infected animals.

Postulates 3 and 4 are extremely important in definite proof of the role of agent in human
disease. However, this depends on the ability to develop animal models that resemble the
human disease. In many cases such models do not exist.

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STEPS INVOLVED IN THE PATHOGENESIS OF THE
BACTERIA:

1. Transmission
2. Colonization
3. Adhesion
4. Invasion
5. Survival in the host
6. Tissue Injury
STEPS INVOLVED IN THE PATHOGENESIS OF THE
BACTERIA:

1. Transmission
§ Potential pathogens may enter the body by various routes, including the respiratory,
gastrointestinal, urinary or genital tracts.
§ Alternatively, they may directly enter tissues through insect bites or by accidental or
surgical trauma to the skin.
§ Many opportunistic pathogens are carried as part of the normal human flora, and this
acts as a ready source of infection in the compromised host (e.g. in cases of AIDS or
when the skin barrier is breached).
§ For many primary pathogens, however, transmission to a new host and establishment
of infection are more complex processes.
STEPS INVOLVED IN THE PATHOGENESIS OF THE
BACTERIA:

2. Colonization
§ The establishment of a stable population of bacteria on the host’s skin or mucous
membranes is called colonization.
§ For many pathogenic bacteria, the initial interaction with host tissues occurs at a
mucosal surface and colonization normally requires adhesion to the mucosal cell
surface.
§ This allows the establishment of a focus of infection that may remain localized or may
subsequently spread to other tissues.
STEPS INVOLVED IN THE PATHOGENESIS OF THE
BACTERIA:
3. Adhesion
§ Adhesion is necessary to avoid innate host defense mechanisms such as peristalsis in the
gut and the flushing action of mucus, saliva and urine, which remove non-adherent
bacteria.
§ For bacteria, adhesion is an essential preliminary to colonization and then penetration
through tissues.
§ Successful colonization also requires that bacteria are able to acquire essential
nutrients—in particular iron—for growth.
§ At the molecular level, adhesion involves surface interactions between specific
receptors on the mammalian cell membrane (usually carbohydrates) and ligands
(usually proteins) on the bacterial surface.
§ The presence or absence of specific receptors on mammalian cells contributes
significantly to tissue specificity of infection.
§ Invasins are a class of proteins associated with the penetration of pathogens into host cells
 Mechanisms of Molecular Pathogenicity
Pathway for S.aures

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SOME BACTERIAL SURFACE LECTINS AND THEIR COGNATE RECEPTORS ON ANIMAL CELLS

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 STRATEGIES FOR ANTI-ADHESION THERAPY
§ Bacterial attachment can be inhibited by interfering with adhesin biosynthesis (A), adhesin
assembly (B), or host receptor assembly (C).
§ Binding can be inhibited by competitive replacement of the adhesin from the host (D) or of the
host receptor from the adhesin (E) using soluble molecules or by using designer microbes (F).
Antibodies against bacterial adhesins can block surface epitopes required for binding (G).

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INHIBITORS OF CARBOHYDRATE-SPECIFIC ADHESION THAT PREVENT
BACTERIAL INFECTION IN VIVO

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STEPS INVOLVED IN THE PATHOGENESIS OF THE
BACTERIA:
4. Invasion
§ Invasion is penetration of host cells and tissues (beyond the skin and mucous surfaces),
and is mediated by a complex array of molecules, often described as ‘invasins’. These
can be in the form of bacterial surface or secreted proteins which target host cell
molecules (receptors).
STEPS INVOLVED IN THE PATHOGENESIS OF THE
BACTERIA:

5. TISSUE INJURY
§ Bacteria cause tissue injury primarily by several distinct mechanisms involving:
§ Exotoxins
§ Endotoxins and non-specific immunity
§ Specific humoral and cell mediated immunity
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