Brucella Bacteria

Classification, Characteristics, Causes/Treatment


Named after David Bruce who first isolated the organism in 1887, Brucella bacteria is a genus that consists of ten (10) species which can be found in terrestrial and marine animals. They are facultative intracellular pathogens responsible for a contagious infection known as brucellosis. 


The ten species that belong to this genus include:

 

  • Brucella abortus
  • B. suis
  • B. canis
  • B. ovis
  • B. neotomae
  • B. microti
  • B. melitensis
  • B. inopinata
  • B. ceti
  • B. pinnipedialis

 



Classification



Kingdom: Bacteria - Characterized by a cell membrane and lacking membrane-bound organelles


Phylum: Proteobacteria - A gram-negative group that consists of various pathogenic bacteria which are characterized lipopolysaccharide in their outermost membrane


Class: Alphaproteobacteria - Gram-negative oligotrophs 


Order: Rhizobiales - Gram-negative bacteria which may be rod-shaped (or coccobacillus). They are aerobic and some species can fix nitrogen. However, others can cause serious infections


Family: Brucellaceae - Aerobic Gram-negative bacteria most of which are chemoorganotrophs in nature. Some of the species can be found in soil while others rely on a host for survival (pathogenic species)


Brucella: Characteristics of the genus Brucella are discussed below in detail

 


Characteristics 



Brucella Bacteria Morphology and Structure

 

As compared to some of the other bacteria, Brucella species are relatively smaller, ranging from 0.5 to 0.7um in diameter and 0.5 to 1.5um in length. With regards to shape, they are very short rods and may appear oval when viewed under the microscope.

For this reason, they are classified as coccobacillus. They are also immotile and therefore lack the conventional flagella found in some motile bacteria. 

As Gram-negative bacteria, Brucella has a thin cell wall with a peptidoglycan layer that is closely associated with the outermost membrane. The outer membrane, on the other hand, consists of a number of proteins and lipoproteins which include Omp10, Omp16, and Omp19 among others.

Here, the number and type of proteins may vary depending on the species. Different types of proteins can also be found in the cell wall with the number and types of these proteins varying between species. Brucella abortus, for instance, has been found to contain more than 75 proteins in its cell wall. 

 

* Compared to some of the other bacteria, Brucella species do not possess plasmids or produce a capsule. Moreover, they do not form endospores at any stage of their life cycle.

 


Ecology/Distribution


The majority of Brucella species are found on land mammals which act as their reservoir. These include B. abortus, B. suis, B. canis, B. microti, B. neotomae, B. melitensis, and B. ovis.

On land, they can be found in a number of mammals including dears, dogs, horses, pigs, camels, and human beings among others. 

Two species are commonly found in marine mammals. These include Brucella ceti and Brucella pinnipedialis which can be found in such marine animals as whales, dolphins, and seals among others.

While a number of Brucella species can infect human beings, it's only Brucella inopinata that is specific to human beings (found in human beings and not any other animal)

Because they depend on different types of land mammals and some marine animals for their survival, Brucella species are well distributed across the globe. However, Brucellosis in animals has been shown to be more prevalent in some regions than others.

In particular, some of the most commonly affected regions include Central Asia, the Middle East, the Mediterranean, and South America. 

 


Species that tend to cause infections include:

 

  • Brucella inopinata
  • B. abortus
  • B. suis
  • B. melitensis
  • B. canis

 


Life Cycle


As intracellular pathogens, Brucella bacteria depend on the host for their survival. Unlike some bacteria that can reproduce outside the host, the life cycle of Brucella species occurs within the cells of the host.

Following the internalization of the bacteria (into the cells of the host), they start dividing and proliferate further in the endoplasmic reticulum. This allows them to increase in number and spread to other cells as the cycle continues. 

For species like Brucella abortus, growth has been shown to be unipolar which may result in asymmetry (where the daughter cells vary in shape or size). 


In general, the life cycle of the Brucella bacterium involves several important stages which include:

 

  • Entry of the bacterium into the host cell 
  • Unipolar growth 
  • Initiation of chromosomal replication - This has only been shown to occur when the bacterium enters the cell
  • Asymmetric division 

 


Brucellosis



Brucella species are responsible for an infection known as brucellosis in both human beings and various animals. As mentioned, different Brucella species can be found in different types of land and marine mammals. Some of these infections can spread from animals to human beings. 

While some bacteria like members of the genus Rickettsia require a vector in order to be transmitted, Brucella species are usually transmitted through direct contact with infected animals, drinking unpasteurized/untreated milk from infected animals, or consuming other raw dairy products and meat from infected animals, etc. 

Here, then, a vector is not involved in spreading the pathogen from animals to human beings. While human to human spread of brucellosis has been reported in several cases (e.g., transmission from mother to infant during breastfeeding), this is very rare.

 

Human infection may also occur through:


·        Wounds or cuts in the skin - Brucella spp. may enter the body through cuts or wounds in the skin especially in cases where an individual is often in contact with infected animals


·        Through the mucous membrane - Where the bacteria are inhaled during contact with infected animals or animal products 


·        Blood transfusion - Extremely rare 

 

* Given that brucellosis can be transmitted from infected animals to human beings, it's classified as a zoonotic disease. For instance, Brucella abortus, which usually infects cattle, can be spread to human beings through the consumption of undercooked meat or untreated/unpasteurized milk. 

 

In the body, when they pass through the mucosal epithelium, Brucella species are first endocytosed by macrophages and dendritic cells. Following contact between the bacterium and macrophages (or dendritic cells), receptor molecules are activated resulting in a cascade of events that result in the internalization of the bacterium. 

Inside the host cell, the bacterium is then enclosed within a membrane to form a compartment commonly known as Brucella-containing vacuole. 

 

While Brucella bacteria can invade and multiply in other cells (non-phagocytic cells), phagocytic cells are the main targets because they are available to engulf the pathogens once they cross the mucosal epithelium. For the bacteria, one of the biggest advantages of invading macrophages is that they are able to avoid an immune response. 

They are able to undergo the initial phase of cell division and increase in number before they spread to other cells. Even in cases where they first invade non-phagocytic cells, they have been shown to survive for a period of about 72 hours before they invade phagocytic cells. 



* During the initial phase of infection, the majority of Brucella cells are destroyed (degraded) when Brucella-containing vacuoles fuse with lysosomes. Generally, about 10 percent of the pathogens survive.


* Because Brucella bacteria are able to survive in environments with low levels of nutrition, they are able to survive inside phagocytic and non-phagocytic cells.

 

While a good number of Brucella bacteria are destroyed/degraded within the phagolysosomes (by enzymes and bactericidal actions of free oxygen radicals etc.), about 10 percent of the population has been shown to survive.

This has been attributed to the ability of these bacterial cells to actively inhibit the lysosomal proteins that are involved in their degradation which also redirecting the Brucella-containing vacuoles to the endoplasmic reticulum where they undergo replication. Moreover, the acidic environment in the vacuole activates genes that allow the bacteria to continue surviving and avoid destruction. 

Apart from macrophages, the pathogens can also invade other suitable cells like dendritic cells through tropism. Here, the bacteria are able to identify and bind to receptors that contain sulfated residues or sialic acid.

As is the case with the phagocytic cells, this binding results in the activation of GTPases which plays an important role in the regulation of the cytoskeletal system during Brucella internalization.

While these cells provide an environment in which the bacteria can replicate and multiply, they also act as carriers that promote spreading of the pathogen in the body.

Like many other pathogenic Gram-negative bacteria, Brucella possesses lipopolysaccharide on their outer membrane. However, the molecule is in the non-classical form when compared to the other lipopolysaccharides. This is beneficial to Brucella because it allows them to invade host cells without inducing an immune response. 

 

Following the initial replication and division in phagocytic cells, Brucella bacteria can spread to invade endothelial and trophoblastic cells. They identify and bind to receptors consisting of sulfated residues and sialic acid (particularly on the surface of epithelial cells).

Again, this results in the activation of GTPases (e.g., Rho and Cdc42) which contributes to the internalization process. 

 

* Unlike epithelial cells, trophoblastic cells become the target for Brucella during gestation (e.g., during the late phase of gestation in ruminants). In these cells, growth is promoted by increased steroid hormone concentration which occurs during the final third stage of gestation. 

 

* Although person-to-person transmission of Brucella is rare, there are estimated 500,000 infections (brucellosis) per year.

 



Causes


By invading non-phagocytic cells, Brucella bacteria have been associated with a number of serious complications that include:

 

Abortion and infertility - In domestic and wild animals, brucellosis has been shown to cause abortion and contribute to infertility. As mentioned, these cells can spread and proliferate in the cells of the reproductive system (e.g., trophoblast).

Brucella abortus, for instance, invades and infects the trophoblastic cells which form the outer layer of the blastocyst a few days after fertilization. By invading these cells and affecting their function, they may cause damage to the reproductive system and even cause an abortion to occur. 

 

* Whereas Brucella abortus can cause abortion in cattle, Brucella suis and Brucella melitensis affect the reproductive tract and may even cause infertility in pigs and sheep respectively.

 

Endocarditis - Although rare, endocarditis is a complication that has been reported among some (between 1 and 11 percent) patients with Brucellosis. This is a serious condition that can cause death among some patients. 

 

Inflammation of the spleen and liver - For patients with brucellosis, hepatocytes are some of the most affected cells. The spread of the Brucella bacteria to the liver has been shown to contribute to apoptosis of these cells (hepatocytes) and consequently to liver damage.

Here, the spleen is also affected as the bacteria continue to spread. One of the most common symptoms here is the enlargement of the liver and spleen. 

 

Epididymitis/ Epididymo-orchitis - Brucella bacteria have also been shown to invade and infect the testicle and epididymis. While the testicle/testis are the glands in which sperm are produced, the epididymis is a long tube in which sperm is stored and transported from the testis. 

These infections are usually characterized by pain and swelling which can prove to be very severe. If not properly managed, this can result in infertility in males. 

 


Some of the other complications associated with brucellosis include:

 

  • Infection of the central nervous system 
  • Arthritis
  • Reduced milk and meat production in cattle and other livestock

 





Treatment

 

As mentioned, Brucella bacteria can be transmitted from animals to human beings through a number of ways including contact with animals, inhalation through the respiratory system as well as through wounds. A number of preventive measures can be taken to reduce the risk. 


These include:

 

·        Properly treating milk from livestock before consuming (boiling or pasteurization etc.)


·        Properly cooking meat and other animals’ products in order to destroy the bacteria (if it's present in these products) - Meat should be cooked until the internal temperature reaches 63 degrees C (at minimum)


·        Vaccinating animals against brucellosis


·        Taking proper care when caring for livestock or other animals


·        Proper handling of animal carcasses, internal organs as well as animal afterbirths 

 


 

Following an infection, however, a number of antibiotics are available for patients. In most cases, Doxycycline and Rifampin are recommended for several weeks. Also, a number of other antibiotics may be prescribed.


These include:


  • Streptomycin
  • Sumycin
  • Trimethoprim
  • Ciprofloxacin




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References



Fabrizio De Massis et al. (2019). Distribution of Brucella field strains isolated from livestock, wildlife populations, and humans in Italy from 2007 to 2015. 

 

Jean Celli. (2019). The intracellular lifecycle of Brucella spp.

 

Xavier De Bolle, Sean Crosson, Jean-Yves Matroule, and Letesson jean-jacques. (2015). Brucella Abortus Cell Cycle and Infection are Coordinate. 

 

Yongqun He. (2012). Analyses of Brucella pathogenesis, host immunity, and vaccine targets using systems biology and bioinformatics. 

 

 

Links 

 

https://www.frontiersin.org/research-topics/170/recent-advances-in-brucella-research

https://www.intechopen.com/books/updates-on-brucellosis/the-interaction-between-brucella-and-the-host-cell-in-phagocytosis

https://www.cdc.gov/brucellosis/treatment/index.html