The Gram-negative Cocci
Year III
Classification
⚫ Neisseriaceae all are Gram negative aerobic rods and
cocci.
⚫ Contains 4 genera:
⚫ Neisseria- cocci
⚫ Moraxella-cocci; other species within the genus are short
rods (coccobacilli)
⚫ Acinetobacter- rods
⚫ Kingella- rods
Neisseria
⚫ General Characteristics
⚫ Gram negative diplococci that are coffee-
bean shaped with adjacent flattened edges.
⚫ Found intracellularly in PMNs or extracellularly.
⚫ Two species- N. meningitidis (MGC) and N. gonorrhoeae
(GC) are pathogenic although N. meningitidis may be
found as part of the nasopharynx normal flora in 10-15% of
the population.
Neisseria gonorrhoeae
⚫ Third most commonly sexually transmitted disease in
USA
⚫ Cell—small Gram negative diplococci
⚫ It does not survive long outside the human body
because it is highly sensitive to dehydration
⚫ Encapsulated
Mechanisms of Pathogenicity
⚫ Pili- important in attachment to human
columnar epithelial cells- may be anti-phagocytic.
⚫ At least twenty gonococcal genes code for pilin, most
of which are not expressed at any given time because
they lack promoters
⚫ By shuffling and recombining chromosomal regions of
these genes, a single strain can at different times
express multiple pilins (gene conversion)
Mechanisms of Pathogenicity
⚫ Gene conversion (GC) allows the organism to produce
antigenically different pilin molecules over time
⚫ If the gene is moved in to unexpression locus so that the
reading frame is shifted no pilin made
⚫ This is called phase variation (PH)
⚫ GC and PH are two mechanisms by which the
gonococcus can avoid the host’s immune response, hence
cause repeated infections in the same individual
Mechanisms of Pathogenicity
⚫ Outer membrane protein (OMP) I- the principal protein found
on the outer membrane- functions as a porin and allows small
molecules to diffuse thru the membrane.
⚫ Studies suggest that it leaves the GC membrane and inserts
into the host membrane, possibly to initiate endocytosis of GC
by epithelial cells of the mucosa.
⚫ GC is transported in vesicles to the base of the cells and
released into subepithelial tissue causing the typical
inflammatory response seen in gonorrhea.
Mechanisms of Pathogenicity
⚫ OMP II- a minor protein found on the outer membrane.
⚫ It may be involved in attachment to PMNs and
other leukocytes.
⚫ It may be involved in resistance to serum killing.
⚫ Both pili and protein II are subject to
antigenic variation, therefore, even if antibodies are
formed against them they are not effective.
⚫ OMP III – an outer membrane protein that may associate
with Protein I to form pores.
Mechanisms of Pathogenicity
⚫ Lipopolysaccharide- endotoxin & causes mucous membrane
damage due to loss of ciliary action and sloughing of ciliated
cells.
⚫ Contain lipid A and core polysaccharide, but no strain-specific
0 side chain
⚫ It also causes fever and toxicity and may undergo antigenic
variation.
⚫ Capsule – helps prevent phagocytosis
⚫ IgA1 protease- cleaves IgA to allow mucosal attachment of
GC.
GC Cell Wall Structure
Mechanisms of Pathogenicity
⚫ Ability to acquire iron from the host by producing outer
membrane proteins that capture it under conditions of iron
limitation.
⚫ Enhanced capacity occurs in those that cause disseminated
gonococcal infection (DGI).
⚫ Strains of GC that cause DGI possess certain types of
Protein I, are resistant to phagocytosis and serum
bactericidal activity, and are able to multiply unchecked in
the presence of PMNs.
⚫ Endotoxin- symptoms of toxemia common.
Clinical Significance
⚫ Usually transmitted by direct sexual contact.
⚫ Used to be the most common reportable disease in the U.S.
⚫ Those infected commonly have a concomitant Chlamydia
trachomatis infection (most common reportable disease in
the U.S. today).
⚫ Asymptomatic infections- Males= 10%, Females= 20-75%.
⚫ The problem with asymptomatic individuals is that they are
carriers and can transmit the disease to others.
Clinical Significance
⚫ Uncomplicated infections - in males incubation= 1-4 days
followed by acute urethritis with profuse purulent discharge
filled with GC.
⚫ If untreated may spread to cause prostitis and epididymitis -
with proper antibiotic treatment this is rare.
⚫ With oropharyngeal infection mild pharyngitis.
⚫ With rectal infection - proctitis;
Clinical Significance of GC
⚫ In females following the incubation may have increased
vaginal discharge, burning or frequency of urination and
menstrual abnormalities.
⚫ Infected mothers can transmit GC to their babies at birth
causing gonococcal ophthalmia neonatorum.
⚫ This can lead to blindness, therefore all babies are
given erythromycin eye drops at birth to prevent this.
Neonatal Ophthalmia Neonatorum
Clinical Significance of GC
⚫ Complicated infections-
⚫ Occur more frequently in women - spread from the
cervix into the fallopian tubes resulting in
endometritis, salpingitis, and peritonitis= pelvic
inflammatory disease (PID).
⚫ Occurs in 10-20% of infected women.
⚫ Symptoms include lower abdominal pain, abnormal
vaginal and cervical discharge, and uterine tenderness.
⚫ This can result in ectopic pregnancy and infertility.
Salpingitis
Complicated Infections of GC
⚫ Spread to the bloodstream may result in DGI in
both men and women (1%).
⚫ Can result in endocarditis, arthritis,
maculopapular rash, and meningitis.
Neisseria meningitidis
⚫ Morphology-Encapulated Gram negative diplococci
⚫ Colonization-Asymptomatically in nasopharnyx of
healthy individuals
⚫ Capsule indicated by large mucoid colonies
⚫ Acid production from glucose and maltose, but not
sucrose or lactose
⚫ Several serotypes known
Pathogenesis
⚫ Pili- allow binding to specific nasopharyngeal receptors.
⚫ Capsule (polysaccharide) – antibodies, if made, are protective.
⚫ Only certain serotype antigens are found during epidemics.
⚫ Ability to acquire iron from human transferrin
⚫ IgA1 Protease
⚫ Class 1,2, and 3 antigens function as porins ( Protein I of GC).
⚫ Class 5 antigens are involved in attachment and antigenic
variation (Protein II of GC).
Serogroups
⚫ Lipooligosaccharide capsule is antigenically diverse,
which has allowed the identification of atleast 14
capsular polysaccharides called serotypes
⚫ Most infections are due to serogroups A, B, C, W and
Y
⚫ Serogroup A is usually responsible for massive
epidemics in developing countries
Serotypes
⚫ Second classification system called serotyping (1,
2…..20)
⚫ But based on the properties of the outer
membrane proteins and LOS
⚫ There is no predicable relationship between the
serogroups and the serotypes
Pathogenesis
⚫ Causes endemic and epidemic cerebral meningitis.
⚫ Most common in children under one year,
adolescents, and young adults.
⚫ Can be part of the normal flora of the
nasopharynx and cause disease when there is a
failure in host resistance or when a particularly
virulent strain colonizes the mucous membranes.
Pathogenesis
⚫ Asymptomatic carriers are the primary source of spread thru
aerosols.
⚫ Invasion of the bloodstream occurs only in individuals lacking
bactericidal antibodies or deficient in certain complement
components (C5-C8).
⚫ Invasion of the bloodstream may result in septicemia
(meningococcemia) or meningitis.
Pathogenesis
⚫ Meningococcemia- symptoms include high fever, shaking,
chills, muscle pain, and petechial rash (hallmark of MGC
infections).
⚫ Disease may be chronic, moderate or fulminant.
⚫ The fulminant type is called the Waterhouse-Friderichsen
syndrome and it is characterized by disseminated intravascular
coagulation (DIC), with hemorrhaging into the skin, adrenal
glands and other internal organs.
⚫ This results in rapid death due to acute generalized toxemia
and shock.
⚫ Most of these symptoms are due to the activity of the
endotoxin.
Pathogenesis
⚫ Meningitis- symptoms include fever, headache,
stiffness of back and neck, and petechial rash.
⚫ In severe cases there is severe cerebral hyperemia
(accumulation of blood) and tissue swelling.
⚫ This is invariably fatal without rigorous antimicrobial
therapy.
Other Neisseria species
⚫ Rarely associated with endocarditis, septicemia, and
meningitis.
⚫ M. catarrhalis - may be a significant cause of otitis
media and maxillary sinusitis in children
⚫ May cause pneumonia and bronchitis in
immunocompromised individuals.
⚫ May also occasionally cause endocarditis, meningitis
and septicemia.
Treatment And Antimicrobial
Susceptibility
⚫ GC - used to use only penicillin.
⚫ Resistant strains are emerging so -lactamase testing
should be done.
⚫ For penicillin resistant strains or penicillin sensitive
individuals substitute ceftriaxone or spectinomycin
for penicillin (1 dose to treat GC) plus 7 days of
doxycycline to treat possible coexisting C.
trachomatis infection.
Treatment
⚫ Amoxicillin or ampicillin or Penicillin G plus
probenecid can be used for uncomplicated cases
⚫ MGC- I.V. penicillin or chloramphenicol and
erythromycin or ceftriaxone.
⚫ Vaccines (tetravalent to polysaccharide capsular
antigens A, C, Y, W135) are available for the virulent
types of MGC.
⚫ Most human infections are due to types A, B, C, Y,
and W135.
⚫ They are given to those at risk.
Neisseria species Gram Stain
Moraxella catarrhalis Gram Stain
Intracellular GC