Actinomyces gerencseriae

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1. Classification

a. Higher order taxa

Domain: Bacteria
Phylum: Actinobacteria
Class: Actinobacteria
Order: Actinomycetales
Family: Actinomycetaceae
Genus: Actinomyces
Species: Actinomyces gerencseriae

2. Description and significance

Actinomyces is a genus of bacteria that consists of a widely varied number of species that can exist both in the soil microbiome as well as within human and animal bodies. The Actinomyces genus mostly consists of Gram-positive bacilli that are facultatively anaerobic or microaerophilic rods. 1 Species from the Actinomyces genus often live primarily within the oral cavities of humans as part of the natural endogenous microbiome, but can become pathogenic when they are able to enter the body through open wounds, such as those stemming from poor dental hygiene. Members of the Actinomyces genus are significant because certain species (primarily A. gerencseriae and A. israelii) are known to cause the disease actinomycosis. Actinomycosis is a chronic and inflammatory granulomatous infection. This infection is referred to as granulomatous due to the granuloma, or inflammation, caused by an accumulation of macrophage immune cells that is a reaction of the host body to the invading pathogen. Actinomycosis can result in abscesses in the mouth, lungs, breast, and gastrointestinal tract in humans. While the incidence of this disease is rare, it can be particularly detrimental if and when it spreads to other tissues. 

Discrimination Between the Different Actinomyces Species
The Actinomyces genus has gone through several examinations and sequencing techniques to identify the different species. A major event involving the species Actinomyces gerencseriae was its distinction from the Actinomyces israelii species, as it was previously known as Actinomyces israelii serotype 2. ⁸ A study published in 1969 underlines the belief that there was a lack of adequate evidence to classify A. israelii Serotype 2 as a different species. Apart from the arabinose fermentation tests, the two serotypes produced very similar results in biochemical tests conducted, and therefore serotype 2 was not recognized as a separate species. ⁹ However, a more recent article discusses the genetic unrelatedness of Actinomyces israelii and Actinomyces gerencseriae. ¹⁰

Cultivation and Isolation of the Genus Actinomyces
The Actinomyces genus has gone through cultivation on different types of organic media including “hormone” agar, blood agar, etc. However, many of the media used were short-lived and inefficient in culturing and isolating the species. The species grows optimally in microaerobic conditions, on blood agar at 37°C. ⁵ Actinomyces gerencseriae specifically cultivate best on blood agar and in peptone-yeast extract-glucose broth. A study done by Howell and Pine described the positive results of culturing and maintaining the species of Actinomyces on a synthetic medium with potato starch. 13 species from the Actinomyces genus were successfully cultivated and maintained in liquid synthetic medium containing potato starch. Through this process of cultivation, it showed that the species of the Actinomyces genus grew best at a pH of 6.5. The growth rates of the bacteria dropped drastically once the pH became more basic.¹¹

3. Genome structure

Actinomyces gerencseriae possesses a GC-rich genome, composed of 70% GC pairs.

The strain type of A. gerencseriae is ATCC 23860 = CCUG 32936 = CCUG 34703 = CDC W 838 = CIP 105418 = DSM 6844 = JCM 12963 = VPI 12594. ²

4. Cell structure

The entirety of the Actinomyces genus consists of gram positive bacteria. These gram positive bacilli bacteria possess cell walls consisting of a large external peptidoglycan layer threaded with teichoic acids and lipoteichoic acids. This peptidoglycan layer is separated from the cell membrane bilayer by the periplasmic space. The cell membrane bilayer is interspersed with important membrane proteins.

When Actinomyces was initially discovered in the late 1800s as a source of oral infection first in cows (A. Bovis) and then humans (A. Israelii), it was mistakenly identified as a fungal genus. The reason for this was the tendency for Actinomyces species to grow in a filamentous manner, and form hyphaes similar to eukaryotic fungi. Although this has been the typical classification of Actinomyces, several more recently discovered of these species lack the ‘typical’ branching rod appearance. ³

Actinomyces gerencseriae is a nonmotile, Gram positive bacterial species. The average Actinomyces gerencseriae colony is around 0.2 mm in diameter, circular in shape, are branching filamentous and white in color. Actinomyces gerencseriae have an incubation period of 2 days and is a non-spore forming bacterial species.

5. Metabolic processes

The ability to metabolize certain substances is an important distinguishing factor for the different Actinomyces species. The primary tests used in research include the ability for nitrate reduction, CAMP test reaction, as well as tests for the production of β-galactosidase, β-NAG, β-xylosidase, and 𝛼-fucosidase. Esculin hydrolysis is also a useful test for distinguishing certain species within the genus. Actinomyces as a genus has also been found to produce lactic acid in addition to succinic acid.

A common problem in recent years after the determination of A. gerencseriae as a separate species from A. israelii has been the separation of the two on a biochemical basis. It has been discovered, however, that these two species can be distinguished by their differential abilities to ferment different metabolites. A. israelii was found to possess the ability to ferment arabinose, while A. gerencseriae cannot. ³ Additional research has showed that these two species show differing abilities in the degradation of two mannopyranoside isomers. A. israelii can degrade the β-mannoside isomer, while A. gerencseriae can degrade the 𝛼-mannoside isomer. ⁴

6. Ecology

The genus normally presents itself in the oral cavity. A study on biofilm growth of the Actinomyces species found that in the presence of Actinomyces gerencseriae, Lactobacillus plantarum and Lactobacillus rhamnosus grew 4-20 times more than in a presence of another bacterial species in the oral community. Lactobacillus plantarum and Lactobacillus rhamnosus are examples of bacterial species commonly found in the oral cavity of humans, and their accelerated growth in this case demonstrate that overall, A. gerencseriae promotes growth in its ecological niche. Actinomyces gerencseriae are primarily microaerophilic, though some strains appear to be anaerobic. The significance of research in this area reveals itself when the features of the Lactobacillus genus, which can tolerate and utilize lactic acid in plaque under anaerobic conditions, are coupled with the growth promoting effects of the Actinomyces genus. Actinomyces promoted the growth of lactobicilli by providing a biofilm matrix. ⁵

7. Pathology

The most common infection related to Actinomyces is actinomycosis. Gram stains for infected tissues are used as the main method for diagnosing actinomycosis. Once Actinomyces infects the host, sulfur granules, which are tiny yellow clumps, create a chronic granulomatous infection. The clump is stabilized by a protein-polysaccharide complex which provides antibiotic resistant properties. ⁶

A study was conducted on the susceptibility of Actinomyces in response to antibiotic treatments. The Actinomyces genus does not respond successfully to conventional root canal therapy like the other microbes that reside in the oral flora, so oral penicillin treatment is recommended first to heal oral diseases. In order to measure the susceptibility of the Actinomyces genus in the oral cavity, researchers collected samples from the periodontal and strained against antibiotics such as amoxicillin, clindamycin, doxycycline, metronidazole, and moxifloxacin. The author used the E-test methodology that provides an antibiotic gradient and circumferential measure of the zone of inhibition. Between the different species in Actinomyces, there was no significant difference as to which was more susceptible. ⁷

8. Current Research

Species of the Actinomyces genus have been important resources for the biopharmaceutical industry, specifically in the discovery of antibiotics. ¹² To have a better understanding of the biodiversity of the genus, many researches have been done in various environments. These environments include marine sediments, plants, desert soils, etc. ¹³ Along with finding the optimal environment for harvesting species of Actinomyces genus, discovery of the optimal harvesting time is extremely important. Many researchers are looking into NMR-based metabolic profiling method to discover the optimal harvesting time for Actinomyces in producing various antibiotics. ¹²

A recent study published in June of 2017 analyzed levels of Actinomyces spp. in cervical exudates from women with cervical intraepithelial neoplasia (CIN) and cervical cancer. Results indicated that the female patients with cervical cancer showed a notably higher prevalence of Actinomyces in cervical exudates than patients with CIN and normal control individuals. Actinomyces was found in 36.6% of females with cervical cancer, while it was found in only 10% of women with CIN and 9% of healthy control women. This study is of particular interest because it brings into question the molecular mechanisms involved in the potential role that bacterial communities play in the onset of cancer. It also poses the question of whether or not cancer has any influence on the prevalence of different bacterial species in patients. Further research must be done as to whether or not the presence or marked increase in the levels of Actinomyces (or a particular species of Actinomyces) in the microbiota could be used to aid in early diagnosis of cervical cancer or other pathological conditions. ¹⁴

9. References

1. Cimmino, T., Metidji, S., Labas, N., Le Page, S., Musso, D., Raoult, D., & Rolain, J.-M. (2016). Genome sequence and description of Actinomyces polynesiensis str. MS2 sp. nov. isolated from the human gut. New Microbes and New Infections, 12, 1–5. http://doi.org/10.1016/j.nmni. 2016.02.014
2. Actinomyces gerencseriae [Fact sheet]. (n.d.). Retrieved November 23, 2017, from National Center for Biotechnology Information website: https://www.ncbi.nlm.nih.gov/ genome/11207
3. Sarkonen, N., Könönen, E., Summanen, P., Könönen, M., & Jousimies-Somer, H. (2001). Phenotypic Identification of Actinomyces and Related Species Isolated from Human Sources. Journal of Clinical Microbiology, 39(11), 3955-3961. https://doi.org/10.1128/JCM.39.11. 3955-3961.2001
4. Maiden, M. F., Tanner, A., & Macuch, P. J. (1996). Rapid characterization of periodontal bacterial isolates by using fluorogenic substrate tests. Journal of Clinical Microbiology, 34(2),376–384.
5. Filoche, S. K., Anderson, S. A. and Sissons, C. H. (2004), Biofilm growth of Lactobacillus species is promoted by Actinomyces species and Streptococcus mutans. Oral Microbiology and Immunology, 19: 322–326. doi:10.1111/j.1399-302x.2004.00164.x
6. Valour, F., Sénéchal, A., Dupieux, C., Karsenty, J., Lustig, S., Breton, P., … Ferry, T. (2014). Actinomycosis: etiology, clinical features, diagnosis, treatment, and management. Infection and Drug Resistance, 7, 183–197. http://doi.org/10.2147/IDR.S39601
7. LeCorn, D. W., Vertucci, F. J., Rojas, M. F., Progulske-Fox, A., & Bélanger, M. (2007). In Vitro Activity of Amoxicillin, Clindamycin, Doxycycline, Metronidazole, and Moxifloxacin Against Oral Actinomyces. Journal of Endodontics, 33(5), 557-560. https://doi.org/10.1016/j.joen. 2007.02.002
8. Smith, A.J., Hall, V., Thakker, B., & Gemmell, C.G. (2005). Antimicrobial susceptibility testing of Actinomyces species with 12 antimicrobial agents. Journal of Antimicrobial Chemotherapy, 56(2), 407-409. https://doi.org/10.1093/jac/dki206
9. Brock, D. W., & Georg, L. K. (1969). Characterization of Actinomyces israelii Serotypes 1 and 2. Journal of Bacteriology, 97(2), 589-593. Retrieved from http://jb.asm.org/content/97/2/ 589.full.pdf
10. Johnson, J. L., Moore, L. V.H., Kaneko, B., & Moore, W. (1990). Actinomyces georgiae sp. nov. , Actinomyces gerencseriae sp. nov. , Designation of Two Genospecies of Actinomyces naeslundii, and Inclusion of A. naeslundii serotypes I1 and I11 and Actinomyces viscosus serotype I1 in A. naeslundii Genospecies 2. International Journal of Systematic and Evolutionary Microbiology, 40(3), 273-286. https://doi.org/10.1099/00207713-40-3-273
11. Howell, A., & Pine, L. (1956). STUDIES ON THE GROWTH OF SPECIES OF ACTINOMYCES I. : Cultivation in a Synthetic Medium with Starch. Journal of Bacteriology, 71(1), 47–53.
12. Wu, C., Zhu, H., van Wezel, G. P., & Choi, Y. H. (2016). Metabolomics-guided analysis of isocoumarin production by Streptomyces species MBT76 and biotransformation of flavonoids and phenylpropanoids. Metabolomics, 12, 90. http://doi.org/10.1007/s11306-016-1025-6
13. Jose, P. A., & Jha, B. (2016). New Dimensions of Research on Actinomycetes: Quest for Next Generation Antibiotics. Frontiers in Microbiology, 7, 1295. http://doi.org/10.3389/fmicb. 2016.01295
14. García-García, A., Coronel-Martínez, J., Leon, D. C., Romero-Figueroa, M. D., Caballero-Pantoja, Y. E., Manzanares-Leal, Et al. (2017). Detection of Actinomyces spp. In cervical exudates from women with cervical intraepithelial neoplasia or cervical cancer. Journal of Medical Microbiology, 66(6), 706-712. doi:10.1099/jmm.0.000485