AGGREGATIBACTER ACTINOMYCETEMCOMITANS: CHARACTERISTICS, MORPHOLOGY, CULTURE - BIOLOGY - 2025

Aggregatibacter actinomycetemcomitans is a bacterium belonging to the Pasteurellaceae family and is part of the group of slow-growing microorganisms called (HACEK). It is not the only species of this genus but it is one of the most important. Formerly this microorganism was classified as an Actinobacillus.

This bacterium, like the species A. aphrophilus, is present in the oral microbiota of humans and primates and has been associated with serious and recurrent infectious processes in the oral cavity, such as aggressive or chronic periodontitis.

Microscopic view of a Gram stain of Aggregatibacter actinomycetemcomitans Source: FisicaGramNegative

However, it has also been involved in extra-oral infections, among which we can mention: endocarditis, bacteremia, wound infections, subphrenic abscesses, brain abscesses, mandibular osteomyelitis, among others.

Most extra-oral infections are due to an invasion of the microorganism from the oral cavity into the interior. This occurs due to the progressive destruction caused by this microorganism in the tissues that make up the insertion and protective periodontium, producing an infection by contiguity.

Fortunately, most of the time this bacterium is susceptible to tetracycline and other antibiotics. However, strains resistant to tetracycline have already been reported, due to the presence of the plasmids tetB.

History

Klinger, in 1912, isolated this microorganism for the first time, who called it Bacterium actinomycetum comitans. In 1921 the name was reduced to Bacterium comitans by Lieske.

Eight years later, the name was modified again, but this time by Topley and Wilson who named it Actinobacillus actinomycetemcomitans. In 1985 Potts reclassified it to the genus Haemophilus (H. actinomycetemcomitans).

Subsequently, thanks to a DNA study carried out in 2006 by Neils and Mogens, a new genus called Aggregatibacter was created, in which this microorganism was included and they named it Aggregatibacter actinomycetemcomitans, being its current name.

Similarly, other bacteria that were previously in the Haemophilus genus, such as: Haemophilus aphrophilus, H. paraphrophilus and H. segnis, were reclassified and fitted into this new genus, due to their genetic similarity.

If we break down the name of the species actinomycetemcomitans, we can see that it is a combination of words.

The term actes means ray, referring to the star shape that the colony of this microorganism presents on the agar.

The word mycetes means mushroom. This term was included because actinomycetes were formerly considered fungi.

Finally, the word comitans means 'common', expressing the intimate relationship between Actinobacillus and Actinomycetem, sometimes causing joint infections.

Taxonomy

Kingdom: Bacteria

Phylum: Proteobacteria

Class: Gammaproteobacteria

Order: Pasteurellales

Family: Pasteurellaceae

Genus: Aggregatibacter

Species: actinomycetemcomitans.

General characteristics

There are 5 well-defined serotypes of this microorganism. These are designated by the letters a, b, c, d and e according to the composition of the O antigen.

There are other serotypes that have not been able to be typed. Serotype (b) is known to be the most virulent and the most frequently isolated of aggressive periodontitis lesions in individuals from the USA, Finland, and Brazil.

Meanwhile, the second most frequent serotype is (c), which has been found mainly in patients from China, Japan, Thailand and Korea. This serotype has been isolated more frequently in extra-oral lesions.

Virulence factors

Virulence factors can be divided into those elements that influence colonization, those that modify the immune response, those that promote tissue destruction and invasion, and those that inhibit tissue repair.

Factors that stimulate colonization

The production of an amorphous extracellular material of a protein nature, together with the adhesion capacity conferred by its fimbriae and the production of adhesins released in its vesicles, play a fundamental role in the formation of biofilms (biofilms) and therefore colonization..

That is why this microorganism is capable of strongly adhering to certain surfaces, such as: glass, plastic and hydroxyapatite, as well as to each other.

Factors that weaken the immune response

Its main virulence factor is represented by the hyperproduction of a leukotoxin, stored and released by cytoplasmic vesicles. As its name indicates, leukotoxin exhibits great cytotoxic activity on leukocytes (polymorphonuclear cells and macrophages).

Notably, vesicles also release endotoxins and bacteriocins. Endotoxins stimulate the production of pro-inflammatory cytokines, while bacteriocins act by inhibiting the growth of other bacteria, creating an imbalance in the oral microbiota in their favor.

Similar to leukotoxin is the cytolethal stretching toxin, or also called cytoskeletal stretching cytotoxin (CDT).

This exotoxin has the ability to block growth, distort morphology, and impede the proper functioning of CD4 lymphocytes. It is also possible that it activates the apoptosis process (programmed cell death) of these cells. In this way the immune response is weakened.

The immune response is also affected due to the inhibition of the opsonization process, since the Fc fractions of the antibodies are attracted by certain proteins located in the cell wall of the microorganism.

This union prevents the complement from doing its job. In addition to this there is inhibition in the synthesis of IgM and IgG antibodies.

Finally, this bacterium also produces substances that inhibit the chemotactic attraction of leukocytes, especially polymorphonuclear cells, as well as preventing the production of hydrogen peroxide in these same cells.

Factors that stimulate tissue destruction and invasion

The capacity for destruction and invasion of tissues that this microorganism possesses is mainly due to the production of epitheliotoxins, collagenases and a protein called GROE1.

The former destroy the intercellular junctions at the level of the hemidesmosomes, the latter destroy the connective tissue of the periodontium, and the third has osteolytic activity (destruction of bone).

To make matters worse, the presence of lipopolysaccharide (LPS) in its cell wall (endotoxin) cannot be ignored.

LPS acts as a stimulant for the production of interleukin 1 (IL-1B), tumor necrosis factor alpha (TNF-α), among other inflammatory mediators, in addition to promoting bone resorption.

On the other hand, it should be noted that there are indications that this bacterium can live and multiply intracellularly, especially within epithelial cells.

Cell invasion occurs in specific sites, such as connective tissue, alveolar bone, intracellular spaces, among others.

Inhibition of damaged tissue repair

In addition to all the aforementioned, this bacterium also produces other cytotoxins that delay the renewal of damaged tissue, by destroying fibroblasts, generating true chaos.

Morphology

Microscopic

It is a Gram negative coccobacillus that does not have flagella, therefore it is immobile. It does not form spores but it does have a capsule and fimbriae. Each bacterium is approximately 0.3-0.5 µm wide and 0.6-1.4 µm long.

In the Gram, a certain pleomorphism can be observed, that is, some individuals are more elongated (coccobacilli) and others shorter (coccoid), the coccobacillary forms predominate over the coctaceous ones when the Gram comes from a culture medium.

While the cocaceous forms predominate when it comes from a direct sample, they are distributed singly, in pairs or forming clumps or clusters.

Macroscopic

The destruction of the tissue progresses rapidly, and can cause important contiguous lesions, such as: brain abscesses, liver abscesses, glomerulonephritis, pleuropulmonary infections, cervical lymphadenitis, among other conditions.

It can reach the blood and cause endocarditis, bacteremia, septic arthritis, endophthalmitis, epidural abscess and infections in the intra-abdominal cavity (subphrenic abscesses).

Endocarditis cases are associated with the presence of a malformation or previous condition in the patient, such as the presence of valvular heart disease or prosthetic valves. On the other hand, this bacterium increases the risk of heart attacks, since it thickens the atheromatous plaque in the coronary arteries.

Treatment

In patients with periodontitis, swish with 0.12-0.2% chlorhexidine can be used as local treatment (oral cavity), 2 times a day for 10-14 days.

In the treatment of periodontitis, it is important to perform a supra-gingival and sub-gingival scaling (above and below the gum respectively) and also a root polishing to smooth the surface, since on a smooth surface it is more difficult for tartar to accumulate.

However, this is not enough and a systemic treatment with antibiotics, such as ciprofloxacin, metronidazole, amoxicillin or tetracycline, is needed.

The use of antimicrobial combinations is recommended for more efficient bacterial eradication. The combinations of amoxicillin and metronidazole or ciprofloxacin with metronidazole have been very useful, but not so that of metronidazole with doxycycline, according to some studies carried out.

This strain generally expresses resistance to penicillin, ampicillin, amikacin, and macrolides.

Prevention

To prevent an infection by this microorganism, it is recommended to take care of and maintain good oral health. For this, it is necessary to visit the dentist regularly and remove dental plaque and tartar with frequent cleanings.

Smoking is a factor that favors periodontal disease, which is why it should be avoided.

References

1. Ramos D, Moromi H, Martínez E, Mendoza A. Aggregatibacter actinomycetemcomitans: Important pathogen in periodontitis. Odontol. Sanmarquina. 2010; 13 (2): 42-45. Available at: Users / Team / Downloads /
2. Flor-Chávez M, Campos-Mancero O. Antibiotic susceptibility of Aggregatibacter actinomycetemcomitans by means of the diffusion and dilution test. Sun Hundred. 2017; 3 (2): 348-374. Available at: Dialnet.com
3. Raja M, Ummer F, Dhivakar CP. Aggregatibacter actinomycetemcomitans - a tooth killer? J Clin Diagn Res. 2014; 8 (8): 13–16. Available from: ncbi.nlm.nih.gov/
4. Malheiros V, Avila-Campos M. Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum in subgingival biofilms of Brazilian patients with and without periodontal disease: comparison of two detection methods. Odontol. Sanmarquina 2018; 21 (4): 268-277. Available at: docs.bvsalud.org/
5. Ardila C, Alzate J, Guzmán I. Association of Aggregatibacter actinomycetemcomitans and red complex microorganisms with clinical parameters in patients with chronic periodontitis. AMC, 2010; 14 (3). Available at: scielo.sld
6. Díaz J, Yáñez J, Melgar S, Álvarez C, Rojas C, Vernal R. Virulence and variability of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans and their association with periodontitis. Rev. Clin. Implantol periodontics. Rehabil. Oral. 2012; 5 (1): 40-45. Available in: scielo.
7. Flores R. Aggregatibacter actinomycetemcomitans. Rev. chil. infectol. 2011; 28 (6): 579-580. Available at: scielo.conicyt