The Bacterium That Has Stumped the World
Cara Tolbert-Blunt
04/07/20
AGSC 321
I.
Introduction
When the Brucella bacteria were first discovered by David Bruce in 1887, it was dubbed
‘Micrococcus melitensis’. Within 2 years, the Mediterranean Fever Commission had identified
the source of the bacteria and the method of infection (Cutler, Whatmore, Commander 1). From
then on, bacteria in the genus Brucella have gone on to become one of the most significant
zoonosis in the public and animal health sector. In fact, this bacteria went on to be studied and
researched in the first publication of the Pathologia Veterinaria, now Veterinary Pathology
(Olsen, Palmer 3). After nearly a century of research on this organism, the search for a vaccine
continues. This review will detail why Brucella suis has confounded researchers in search of a
cure for years.
II.
General Overview of Swine Brucellosis
Swine brucellosis is a disease caused by the bacterium Brucella suis, commonly biovars 1
and 3. It is primarily a venereal disease that can also be transmitted through ingestion of infected
tissues or contact with infected body fluids such blood or semen. Currently, there is no available
treatment, vaccine, or reliable preventative for swine brucellosis. Research shows that pigs who
are exposed to B. suis develop infection in their blood which eventually localize in the various
tissues of the body (USDA 2018). After the B.suis infection sets in, usually inflammatory
lesions occur in the reproductive organs. This eventually leads to abortions, infertility, and low
milk production (USDA 2018). It is easy to understand why this seemingly incurable disease
would be a high priority to cure in the agricultural industry because of the threat to profit
margins it poses. Loss of livestock or weak offspring would a devastating blow to many smalltime farmers. Even worse still, brucellosis is zoonotic, posing a threat to human health as well. In
humans, brucellosis presents as a typical febrile illness accompanied by swelling in the joints.
Well over half of a million cases per year are reported worldwide, but experts suspect the
number to be much higher due to the nonclinical signs of brucellosis (Olsen, Palmer 2014). The
only hope the industry has at preventing this disease lies in the mitigation of the threat reservoir
hosts pose to domestic and commercial herds.
III.
Genetic Characteristics & Intracellular Interactions
The Brucella bacteria are believed to have originated from soil-dwelling bacteria that
eventually evolved to parasitic facultative intracellular organisms. Modern day brucellae are
divided into six species of gram-negative bacteria, which are further categorized into biovars that
are determined by metabolic characteristics. (Olsen and Tatum 2016). This drastic evolution has
allowed the Brucella bacteria to become as pathogenic as they have. Unlike most other bacteria,
Brucella suis have evolved by exchanging as little genetic information with other bacteria as
possible and lack plasmids. It has been stated that the reason for this is due to the bacterium’s
preference to remain inside of one host in a protected intracellular niche (Cutler, Whatmore,
Commander 2005). The intracellular niche B. suis chooses tends to be inside of the endoplasmic
reticulum of phagocytic cells, epithelial cells, or reproductive organs. (Olsen and Tatum 2016).
B. suis is fond of environments like this because it induces the secretion of the virB operon
which causes the pH of the phagosome to become neutral. After this process, the bacteria start to
replicate. The host organism’s phagosome has now become a brucellosome (Commander, Cutler,
Whatmore 2005). Due to the processes initiated by the brucellosome, fusion with other
lysosomes is now impossible. This prevents cell mediated lysis of the brucellosome and is the
reason B. suis infections are able to persist chronically in a host. The smooth surfaced strain of
Brucella suis produces the antigen LPS which has an o-side chain that allows the bacteria to trick
the cell’s pathogen recognition receptors into malfunctioning, provide a sort of protection from
oxidative killing. (Olsen and Tatum 2016). These factors make it very hard for researchers to
develop a vaccine for this disease, and for the animals’ bodies to fight it off and develop
immunity.
IV.
Diagnosing Swine Brucellosis
The method we have had the most success with in diagnosing swine brucellosis is serology
of the LPS from smooth strains of B. suis (Commander, Cutler, Whatmore 2005). This means
that researchers look for the O-antigenic side of the LPS chain in Brucella. One of the major
problems with this method is that the O-antigenic side of the LPS chain in B. suis is very similar
to the genetic composition of other bacteria. Therefore, our tests for diagnosing swine brucellosis
are not very specific. Due to the inadequacies of serological testing, more effort is being directed
towards research in antigen detection. But this form of testing is not without its flaws either.
When pigs are first exposed to B. suis they typically show very low numbers of brucellae in their
blood, and detection is only accurate during acute stages of infection (Commander, Cutler,
Whatmore 2005). However, in combination with PCR testing we can now detect Brucella
quicker and with more specificity (Commander, Cutler, Whatmore 2005). Another advantage of
utilizing PCR testing is the ability to distinguish the difference between wild type and mutant
strains of Brucella. Yet there is also another drawback to this method. Even though PCR testing
makes it easier and is more sensitive, this method is still only effective in current acute outbreaks
where both milk, abortion material, and tissues can be collected for testing. Proper precautions
must be made against laboratory contamination and accidental infection of researchers.
V.
Vaccines
Researchers have been searching for a vaccine or treatment to swine brucellosis for many
years. Unfortunately, due to the way the bacteria have evolved to replicate, a cure has continued
to elude the scientific community. One potential avenue for development of vaccines are
nonliving vaccines (Commander, Cutler, Whatmore 2005). Researchers have decided to pursue
this method because using live vaccines does not guarantee that the bacteria will not return to
virulence inside of the host after inoculation. There is also a chance that vaccinated organisms
will transmit the disease to vulnerable organisms that cannot be vaccinated, such as those that are
pregnant (Commander, Cutler, Whatmore 2005). Therefore researchers are expending more
effort into researching nonliving vaccines. They have found that it is not sufficient to vaccinate
only once to form a continued immunity to swine brucellosis. And localized reactions at the site
of inoculation often occur, along with production of antibodies that tamper with the efficacy of
serological testing (Commander, Cutler, Whatmore 2005). There is some hope yet for nonliving
vaccines, though. Now that our understanding of postgenomics, immunological understanding,
and new vaccination delivery systems have grown, it seems likely that researchers will rectify
the weak areas of nonliving vaccines. The best method of prevention we have of swine
brucellosis is the containment of reservoir hosts, such as feral hogs.
VI.
Summary and Discussion
The question man y of us in the agricultural industry are asking is “What can we do now?”
B.suis still remains a threat to human health worldwide. The task for researchers and scientists
now is to improve serological testing, our cheapest and more reliable method of testing. It is also
very important for us to refine our methods of vaccinations. Although our understanding of
Brucella suis has grown over the last few decades, further strides in genome sequencing and
more advanced biotechnology are required before we will be able to confidently administer a
cure for this devasting disease.
Works Cited
Brucella suis Infection Associated with Feral Swine Hunting in 3 States, 2007-2008. (2009).
Centers for Disease Control and Prevention.
Cutler, S. J., Whatmore, A. M., & Commander, N. J. (2005). Brucellosis - New Aspects of an
Old Disease. Journal of Applied Microbiology, 98(6), 1270–1281. doi:
10.1111/j.1365-2672.2005.02622.x
Free, R., & Korslund, J. A. (2018). What is Swine Brucellosis? USDA.
Olsen, S. C., & Tatum, F. M. (2016). Swine Brucellosis; Current Perspectives. Veterinarian
Medicine; Research and Reports.
Olsen, S. C., & Palmer, M. V. (2014). Advancement of Knowledge of Brucella Over the Past
50 Years. Veterinary Pathology, 51(6), 1076–1089. doi: 10.1177/0300985814540545