Microbiology of Genital Ulcer Etiology

Genital ulcer disease is characterized by a disruption of the skin and/or mucosal layer
of the genital region. The majority patients who present with genital ulcers have
herpes, syphilis, or chancroid. Less common cause of genital ulcers include
lymphogranuloma venereum and donovanosis.
1. Syphilis: Treponema pallidum (Family: spirochaetaceae)

Treponemes are helically coiled, corkscrew-shaped cells, 6 to 15 m long and

0.1 to 0.2 m wide. They have an outer membrane which surrounds the
periplasmic flagella, a peptidoglycan-cytoplasmic membrane complex, and a
protoplasmic cylinder. Multiplication is by binary transverse fission.
Treponemes have not yet been cultured in vitro.
Treponema pallidum is a fastidious organism that exhibits narrow optimal
ranges of pH (7.2 to 7.4) and temperature (30 to 37C). It is rapidly inactivated
by mild heat, cold, desiccation, and most disinfectants. Traditionally this
organism has been considered a strict anaerobe, but it is now known to be
microaerophilic.
The organism has an outer membrane containing an extremely low density of
surface-exposed transmembrane proteins. Typically, three flagella originate
from each end of the bacterium, and, winding about the bacterium within the
periplasmic space, overlap at the midpoint. The presence of peptidoglycan in
the cell wall, originally surmised on the basis of the bacterium's exquisite
sensitivity to penicillin, has been confirmed by biochemical analysis.
Pathogenesis
Treponemes are highly invasive pathogens which often disseminate relatively
soon after inoculation. Evasion of host immune responses appears to be, at
least in part, due to the unique structure of the treponemal outer membrane
(i.e., its extremely low content of surface-exposed proteins). Although
treponemes lack classical lipopolysaccharide (endotoxin), they possess
abundant lipoproteins which induce inflammatory processes.

2. Chancroid: Haemophilus ducreyi (Family: Pasteurellaceae)

The agent is a fastidious facultative anaerobic, gram negative, non spore-

forming, cocobaccillus. It is 1.5 m long and 0.5 m wide. H. ducreyi grows
best in microaerophilic conditions at 33-35C in a humid atmosphere
containing 5% CO2.
The cell wall of H.ducreyi contains lipooligosaccharides. Usually, gram
negative bacteria cell walls contain lipopolysaccharides, but the H. ducreyi
cell wall lacks the O-antigen. The two type strains are differentiated by
saccharide chain length: the more common strain expresses a nonasaccharide
and the other express a pentasaccharide.
Virulence factor:
- cytolethal distending toxin: ulcer formation
- hemolysin
- causing the host to produce IL-8 and IL-6
3. Donovanosis: Klebsiella granulomatis (Family: Enterobacteriaceae)

K. granulomatis was previously known as Calymmatobacterium granulomatis.

Klebsiella spp. are Gram-negative, nonmotile, usually encapsulated rod-
shaped bacteria, belonging to the family Enterobacteriaceae. These bacteria
produce lysine decarboxylase but not ornithine decarboxylase and are
generally positive in the Voges-Proskauer test. Members of the
Enterobacteriaceae family are generally facultatively anaerobic, and range
from 0.3 to 1.0 mm in width and 0.6 to 6.0 mm in length. Klebsiella spp. often
occur in mucoid colonies. The genus consists of 77 capsular antigens (K
antigens), leading to different serogroups. K. granulomatis are sexually
transmitted. They may also be vertically transmitted (from mother to child) or
by accidental inoculation. Transmission rates between partners are low (<50%)
compared to other sexually transmitted diseases.

4. Lymphogranuloma venereum: Chlamydia trachomatis (Family:

Chlamydiaceae)

C. trachomatis, of the Chlamydiaceae family, is a nonmotile, gram negative,

obligate intracellular pathogen that is around 0.3-1 m in diameter.
Chlamydial species have a unique and complex biphasic life cycle, where they
are infectious during only one life stage. They have an elementary body form
which is adapted for extracellular survival and a reticulate body form which is
involved in intracellular growth and replication. There are 18 serovars of C.
trachomatis; 4 serovars cause trachoma, 5 serovars cause lymphogranuloma
venereum (LGV) and the remainder cause a variety of other sexually
transmitted infection.

Chlamydia trachomatis begin colonization using sialic acid receptors as

binding sites in epithelial cells of the genitalia. Apparently, these sites are not
accessible to phagocytes, T-cells, or B-cells. The pathogen also exists as 15
different serotypes, although only two of them (D and K) cause the sexually
transmitted disease. C. trachomatis has a unique cell wall structure which
enables it to inhibit phagolysosome fusion within phagocytes. The bacterium
is Gram-negative due to an outer lipopolysaccharide membrane, but lacks
peptidoglycan in its cell wall.

5. Herpes: Herpes simplex virus

Of the more than 100 known herpes viruses, 8 routinely infect only humans:
herpes simplex virus types 1 and 2, varicella-zoster virus, cytomegalovirus,
Epstein-Barr virus, human herpesvirus 6 (variants A and B), human
herpesvirus 7, and Kaposi's sarcoma virus or human herpesvirus 8.
Structure
Herpes viruses have a unique four-layered structure: a core containing the
large, double-stranded DNA genome is enclosed by an icosapentahedral capsid
which is composed of capsomers. The capsid is surrounded by an amorphous
protein coat called the tegument. It is encased in a glycoprotein-bearing lipid
bilayer envelope.
Classification
Herpesviruses are divided into three groups: The herpesviruses, herpes
simplex virus types 1 and 2, and varicella-zoster virus, have a short replicative
cycle, induce cytopathology in monolayer cell cultures, and have a broad host
range; herpesviruses, cytomegalovirus, and human herpesviruses 6 and 7,
with a long replicative cycle and restricted host range; and herpesviruses,
Epstein-Barr virus and human herpesvirus 8, with a very restricted host range.
Pathogenesis
The virus replicates initially in epithelial cells, producing a characteristic
vesicle on an erythematous base. It then ascends sensory nerves to the dorsal
root ganglia, where, after an initial period of replication, it establishes latency.
During reactivated infection, the virus spreads distally from the ganglion to
initiate new cutaneous and/or mucosal lesions.