Aggregatibacter actinomycetemcomitans explained

Aggregatibacter actinomycetemcomitans is a Gram-negative, facultative anaerobe, nonmotile bacterium that is often found in association with localized aggressive periodontitis, a severe infection of the periodontium. It is also suspected to be involved in chronic periodontitis.^[1] Less frequently, A. actinomycetemcomitans is associated with nonoral infections such as endocarditis. Its role in aggressive periodontitis was first discovered by Danish-born periodontist Jørgen Slots, a professor of dentistry and microbiology at the University of Southern California School of Dentistry.

'Bacterium actinomycetem comitans' was first described by Klinger (1912) as coccobacillary bacteria isolated with Actinomyces from actinomycotic lesions in humans. It was reclassified as Actinobacillus actinomycetemcomitans by Topley & Wilson (1929) and as Haemophilus actinomycetemcomitans by Potts et al. (1985). The species has attracted attention because of its association with localized aggressive periodontitis.^[2]

Nomenclature

Recent studies have shown a phylogenetic similarity of A. actinomycetemcomitans and Haemophilus aphrophilus, H. paraphrophilus, and H. segnis, suggesting the new genus Aggregatibacter for them.

Importance

It is one of the bacteria that might be implicated in destructive periodontal disease. Although it has been found more frequently in localized aggressive periodontitis,^[3] prevalence in any population is rather high. It has also been isolated from actinomycotic lesions (mixed infection with certain Actinomyces species, in particular A. israelii). It possesses certain virulence factors that enable it to invade tissues, such as the pore-forming toxin leukotoxin A. It has also been isolated from women with bacterial vaginosis and as an etiologic agent in endocarditis.^[4] The pore-forming toxin LtxA of A. actinomycetemcomitans may be a trigger of the autoimmune disease rheumatoid arthritis due to its ability to stimulate protein citrullination, a post-translational protein modification targeted by autoantibodies in this disease.^{[5] [6]}

Virulence factors

• Leukotoxin A: kills granulocytes, monocytes, and other white blood cells expressing integrin beta-2 (CD18)
• Cytolethal distending toxin
• Immunosuppression factors that inhibit blastogenesis, antibody production, and activate T-suppressor cells
• Inhibition of granulocyte functions
• Resistant to complement-mediated killing
• Lipopolysaccharides
• Surface antigens
• Heat shock proteins
• Antimicrobial resistance

A. actinomycetemcomitans serotypes

• a strain, for example ATCC 29523, frequently in oral cavity, variable leukotoxin expression
• b strain Y4, most frequently in localized aggressive periodontitis, high leukotoxin expression; of the b subset, clone Jp2 is particularly leukotoxic^[7]
• c strain ATCC 33384, low leukotoxin expression
• serotypes d, e, f, g
• within each serotype, leukotoxin expression can be highly variable between strains

Small RNA

In bacteria, small RNAs are involved in gene regulation. Jorth et al. identified 9 sRNA by Northern blotting from computer-predicted candidates in strain VT1169 and 202 sRNA by RNA seq in strain 624.^{[8] [9]} A systematic screen by RNA-seq and RT-PCR in HK1651 strain (a clinical isolate from an aggressive periodontitis patient), quantified 70 sRNAs and further identified 17 differentially expressed sRNAs during growth phases.^[10] Target prediction indicated possibility of sRNA interaction with several virulence genes. This study confirmed the presence of one of previously identified Fur regulated sRNAs JA04 identified in strain HK1651.

See also

• List of bacterial vaginosis microbiota
• Oral microbiology

External links

• Type strain of Aggregatibacter actinomycetemcomitans at BacDive – the Bacterial Diversity Metadatabase

Notes and References

1. Henderson B, Ward JM, Ready D . Aggregatibacter (Actinobacillus) actinomycetemcomitans: a triple A* periodontopathogen? . Periodontology 2000 . 54 . 1 . 78–105 . October 2010 . 20712635 . 10.1111/j.1600-0757.2009.00331.x .
2. Nørskov-Lauritsen N, Kilian M . Reclassification of Actinobacillus actinomycetemcomitans, Haemophilus aphrophilus, Haemophilus paraphrophilus and Haemophilus segnis as Aggregatibacter actinomycetemcomitans gen. nov., comb. nov., Aggregatibacter aphrophilus comb. nov. and Aggregatibacter segnis comb. nov., and emended description of Aggregatibacter aphrophilus to include V factor-dependent and V factor-independent isolates . International Journal of Systematic and Evolutionary Microbiology . 56 . Pt 9 . 2135–46 . September 2006 . 16957111 . 10.1099/ijs.0.64207-0 . free .
3. Slots J . The predominant cultivable organisms in juvenile periodontitis . Scandinavian Journal of Dental Research . 84 . 1 . 1–10 . January 1976 . 1061986 . 10.1111/j.1600-0722.1976.tb00454.x .
4. Africa CW, Nel J, Stemmet M . Anaerobes and bacterial vaginosis in pregnancy: virulence factors contributing to vaginal colonisation . International Journal of Environmental Research and Public Health . 11 . 7 . 6979–7000 . July 2014 . 25014248 . 4113856 . 10.3390/ijerph110706979 . free .
5. Konig MF, Abusleme L, Reinholdt J, Palmer RJ, Teles RP, Sampson K, Rosen A, Nigrovic PA, Sokolove J, Giles JT, Moutsopoulos NM, Andrade F . Aggregatibacter actinomycetemcomitans-induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis . Science Translational Medicine . 8 . 369 . 369ra176 . December 2016 . 27974664 . 5384717 . 10.1126/scitranslmed.aaj1921 .
6. Abbasi J . To Prevent Rheumatoid Arthritis, Look Past the Joints to the Gums . JAMA . 317 . 12 . 1201–1202 . March 2017 . 28273301 . 10.1001/jama.2017.0764 .
7. Haubek D . The highly leukotoxic JP2 clone of Aggregatibacter actinomycetemcomitans: evolutionary aspects, epidemiology and etiological role in aggressive periodontitis . APMIS. Supplementum . 118 . 130 . 1–53 . September 2010 . 21214629 . 10.1111/j.1600-0463.2010.02665.x . 20882401 .
8. Jorth P, Whiteley M . Characterization of a novel riboswitch-regulated lysine transporter in Aggregatibacter actinomycetemcomitans . Journal of Bacteriology . 192 . 23 . 6240–50 . December 2010 . 20889741 . 2981213 . 10.1128/JB.00935-10 .
9. Jorth P, Trivedi U, Rumbaugh K, Whiteley M . Probing bacterial metabolism during infection using high-resolution transcriptomics . Journal of Bacteriology . 195 . 22 . 4991–8 . November 2013 . 23974023 . 3811578 . 10.1128/JB.00875-13 .
10. Oogai Y, Gotoh Y, Ogura Y, Kawada-Matsuo M, Hayashi T, Komatsuzawa H . Small RNA repertoires and their intraspecies variation in Aggregatibacter actinomycetemcomitans . DNA Research . 25 . 2 . 207–215 . December 2017 . 29211829 . 5909427 . 10.1093/dnares/dsx050 .