​​​Aeromonas salmonicida

By Ge Gao and Gloria Van

Introduction

1894, Emmerich and Weibel documented the first outbreak of Aeromonas salmonicida in trout fish. This bacterial pathogen found in marine and fresh-water environments is well-known for causing furunculosis. Furunculosis is a disease that commonly affects salmonid fish such as salmon, trout, and whitefish. At first, scientists believed A. salmonicida was an exclusive pathogen to salmonids. We know now that this bacterium is capable of causing furunculosis and several other diseases among salmonids and non-salmonids species. For over 100 years, this bacteria has globally caused declines in fish hatcheries and extreme financial losses. 

Figure 1: Appearance of A. salmonicida on a blood agar plate. Source: Menanteau-Ledouble et al., 2016

Disease

The severity of A. salmonicida depends on many factors; environmental conditions, its interactions with other organisms, stress levels of fish, and the strength of fish immune systems. Ultimately, A. salmonicida is a clever pathogen that targets fish with wounds or weak immune systems.

They enter fish through their skin, gut, or gills. Once inside, they duplicate themselves in phagocytic cells such as macrophages. Macrophages are important cells of the immune system that are responsible for digesting and destroying pathogens. Their duplication leads to the spread of bacteria across the brain, kidneys, liver, and spleen. Eventually, A. salmonicida leads to furunculosis by suppressing the response of leukocytes. Leukocytes are white blood cells, necessary immune cells that fight off infection and disease. Infected fish showcase a variety of internal and external symptoms such as swollen skin lesions, skin abscesses under the skin called furuncles, intestinal inflammation, and lack of energy/movement.

Figure 2: Summary of infection by A. salmonicida. Source: Gloria Van, 2021

The disease is highly contagious and spreads through the water column and direct contact with infected fishes or its eggs. Cases are most frequently reported in fish hatcheries but can occur in wild populations. Unfortunately, most infected fish will die, some without showing any symptoms at all. Since the optimum growth for most strains of A. salmonicida is not 37℃, human infections are very rare.

Epidemiology

A. salmonicida has a worldwide distribution, most commonly causing furunculosis among fish hatcheries. Controlling this bacterium is challenging. Some countries have succeeded, while others continue to struggle.

In 1963, Switzerland and Germany successfully eliminated all traces of furunculosis through strict regulations and increasing the frequency of their inspections. They continue to maintain these standards to avoid any re-introduction of furunculosis. Australia and New Zealand took a different approach by avoiding the importation of any new fish or eggs. On the other hand, furunculosis is still a problem in the United States and many other countries in Europe, such as Sweden and Denmark.

Cases in Salmonids are more likely to be reported and researched due to their popularity and economic importance. As our knowledge of A. salmonicida continues to grow, we now understand that it can infect almost every fish species. For instance, regions where the bacterium was previously absent, such as Japan and regions of mainland Asia have reported A. salmonicida cases. Therefore, it is likely that furunculosis cases are much higher because they are under-reported and under-investigated.

Virulence Factors

The mechanisms of A. salmonicida are complex and consist of multiple virulence factors. The three main factors are the additional layer (A-layer), extracellular products (ECP), and a Type III secretion system (T3SS).

  1. The A-layer is an additional layer on the cell surface that helps A. salmonicida attach to fish macrophages and protects the bacteria from the fish’s immune system defense mechanisms. Therefore, this allows the bacterium to duplicate in the fish undetected.
  1. ECP are secreted molecules such as proteins and enzymes. One example is proteases which are enzymes that degrade proteins. Proteases assist the growth of the bacterium by stealing nutrients from the fish. Stealing nutrients leads to skin lesions which are abnormal appearances of skin that appear discoloured and patchy. A. salmonicida produces many different types of proteases, one being AspA. AspA degrades muscle tissue which causes furuncles, skin abscesses under the skin filled with pus. 
  1. T3SS inserts toxic proteins inside fish cells which results in cell lysis. Cell lysis is when the outer membrane breaks down, and intracellular components like DNA, RNA, and proteins are released. This process creates an imbalance in the cell environment which often leads to cell death. T3SS has three major structures:  (1) A secretion apparatus that assists the delivery between protein toxins and their effector, (2) an injection needle that brings the toxic proteins to the outside of fish cells, and (3) a translocation tool responsible for the physical movement of the toxins, transferring them from the needle into the fish cell.
Figure 3: Depiction of a virulence factor – the A-layer. Source: Ge Gao, 2021
Figure 4: Schematic overview of the Type III secretion system (T3SS). Source: Frey & Origgi, 2016

Treatment

Prevention is one of the most important treatment strategies as infected fish are highly contagious and hard to control. Scientists have tried many strategies such as selective breeding, vaccinations, and antibiotics. 

Selective breeding is when parents are specifically picked to produce offspring with advantageous traits for survival and reproduction. Since 1954, scientists have worked on breeding fish that are resistant to diseases caused by A. salmonicida. The results were mixed. They observed when some fish developed slowly, they were more resistant to developing the disease. Overall, many fish have very different responses to selective breeding. This strategy is considered somewhat effective but not enough alone.

Vaccine development for furunculosis began in the 1940s. Many different types of commercialized vaccines were produced. Unfortunately, none were considered effective in controlling furunculosis. Not until a breakthrough occurred in the late 1900s using oil-adjuvant injection vaccines. This type of vaccine contains an ingredient, oil-in-water, which creates an even stronger immune response in fish against A. salmonicida. Oil-adjuvant vaccines are generally accepted and applied in the fish industry. 

Antibiotics were introduced in 1952 to treat furunculosis. By the late 1990s, they were the most widely used treatment. Similar to vaccines, there is a wide range of antibiotics available. Antibiotics are effective but there are ongoing concerns about antibiotic resistance. 


All treatments have their pros and cons. There is no standard treatment that works for all cases of A. salmonicida. The best solution remains to be prevention which is why new approaches for vaccine development continue.

References

Bartkova, S., Leekitcharoenphon, P., Aarestrup, F. M., & Dalsgaard, I. (2017). Epidemiology of Danish Aeromonas salmonicida subsp. Salmonicida in Fish Farms Using Whole Genome Sequencing. Frontiers in Microbiology, 8, 2411. https://doi.org/10.3389/fmicb.2017.02411

Chart, H., Shaw, D. H., Ishiguro, E. E., & Trust, T. J. (1984). Structural and immunochemical homogeneity of Aeromonas salmonicida lipopolysaccharide. Journal of Bacteriology, 158(1), 16–22. https://doi.org/10.1128/jb.158.1.16-22.1984

Cipriano and Bullock—Furunculosis And Other Diseases Caused By Aeromona.pdf. (n.d.). Retrieved November 18, 2021, from https://webharvest.gov/peth04/20041029064735/http:/www.lsc.usgs.gov/FHB/leaflets/FHB66.pdf

Dallaire-Dufresne, S., Tanaka, K. H., Trudel, M. V., Lafaille, A., & Charette, S. J. (2014). Virulence, genomic features, and plasticity of Aeromonas salmonicida subsp. Salmonicida, the causative agent of fish furunculosis. Veterinary Microbiology, 169(1), 1–7. https://doi.org/10.1016/j.vetmic.2013.06.025

Frey, J., & Origgi, F. C. (2016). Type III Secretion System of Aeromonas salmonicida Undermining the Host’s Immune Response. Frontiers in Marine Science, 3, 130. https://doi.org/10.3389/fmars.2016.00130

Fyfe, L. A., Finley, A., Coleman, G., & Munro, A. L. S. (1986). A study of the pathological effect of isolated Aeromonas salmonidda extracellular protease on Atlantic salmon, Salmo salar L. Journal of Fish Diseases, 9(5), 403–409. https://doi.org/10.1111/j.1365-2761.1986.tb01033.x

Garduño, R. A., Moore, A. R., Olivier, G., Lizama, A. L., Garduño, E., & Kay, W. W. (2000). Host cell invasion and intracellular residence by Aeromonas salmonicida: Role of the S-layer. Canadian Journal of Microbiology, 46(7), 660–668. https://doi.org/10.1139/w00-034

Horne, J. H. (1928). Furunculosis in Trout and the Importance of Carriers in the Spread of the Disease1. Epidemiology & Infection, 28(1), 67–78. https://doi.org/10.1017/S0022172400009396

Janda, J. M., & Abbott, S. L. (2010). The Genus Aeromonas: Taxonomy, Pathogenicity, and Infection. Clinical Microbiology Reviews, 23(1), 35–73. https://doi.org/10.1128/CMR.00039-09

Lee Herman, R. (1968). Fish Furunculosis 1952–1966. Transactions of the American Fisheries Society, 97(3), 221–230. https://doi.org/10.1577/1548-8659(1968)97[221:FF]2.0.CO;2

Menanteau-Ledouble, S., Kumar, G., Saleh, M., & El-Matbouli, M. (2016). Aeromonas salmonicida: Updates on an old acquaintance. Diseases of Aquatic Organisms, 120(1), 49–68. https://doi.org/10.3354/dao03006

Midtlyng, P. J. (1997). 15—Vaccination Against Furunculosis. In E.-M. Bernoth, A. E. Ellis, P. J. Midtlyng, G. Olivier, & P. Smith (Eds.), Furunculosis (pp. 382–404). Academic Press. https://doi.org/10.1016/B978-012093040-1/50020-8

Reith, M. E., Singh, R. K., Curtis, B., Boyd, J. M., Bouevitch, A., Kimball, J., Munholland, J., Murphy, C., Sarty, D., Williams, J., Nash, J. H., Johnson, S. C., & Brown, L. L. (2008). The genome of Aeromonas salmonicida subsp. salmonicida A449: Insights into the evolution of a fish pathogen. BMC Genomics, 9(1), 427. https://doi.org/10.1186/1471-2164-9-427

Sakai, D. K. (1985). Loss of virulence in a protease-deficient mutant of Aeromonas salmonicida. Infection and Immunity, 48(1), 146–152. https://doi.org/10.1128/iai.48.1.146-152.1985

Scott, M. (1968). The pathogenicity of Aeromonas salmonicida (Griffin) in sea and brackish waters. Journal of General Microbiology, 50(2), 321–327. https://doi.org/10.1099/00221287-50-2-321

Valderrama, K., Soto-Dávila, M., Segovia, C., Vásquez, I., Dang, M., & Santander, J. (2019). Aeromonas salmonicida infects Atlantic salmon (Salmo salar) erythrocytes. Journal of Fish Diseases, 42(11), 1601–1608. https://doi.org/10.1111/jfd.13077

Wiklund, T., & Dalsgaard, I. (1998). Occurrence and significance of atypical Aeromonas salmonicida in non-salmonid and salmonid fish species: A review. Diseases of Aquatic Organisms, 32(1), 49–69. https://doi.org/10.3354/dao032049

Woo—1999—Protozoan and metazoan infections.pdf. (n.d.). Retrieved November 18, 2021, from https://dlib.library.razavi.ir/bitstream/Ebook/89557/2/0851991947.pdf#page=67

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