Virulence and Pathogenesis, Treatment and Prevention
InstitutionVirulence and Pathogenesis, Treatment and Prevention
of Opportunistic Bacterial Infections
We live in a day that was much like 100 years ago, before antibiotics existed at all. The reason for this is that almost as soon as a new antibiotic is introduced, bacteria develop resistance to it. In 2008, a type of bacteria was found in China that has 45 specific genes meant solely to confer resistance to antibiotics just in its plasmid. Plasmid is a cellular material generated by bacterial colonies that are hard to penetrate with antibiotics, even without resistance genes (Lutz, 2016). As the search for new methods of treatment continues, it becomes more important than ever before to concentrate on the pathogenesis and specific virulence factors of not just different genus’, but individual strains of each bacteria.
Pathogenesis, simply explained, is the ability and qualitative ways that a bacterium can become a pathogen to its host, in this case a human body. The way that pathogens work on the host makes up its pathogenesis, and is determined by virulence factors. Virulence itself is the quantitative ability of ways that bacteria can impact the host. It is also measurable by how quickly a person is harmed do to how many ways the host is infected. Standard virulence theories apply to opportunistic pathogens in a logical way, meaning that a host can be harmed faster by an opportunistic infection than by one that is commensal. As logical as the theories are, they do not seem to be biologically accurate (Brown, Cornforth, and Mideo, 2012). New theories have emerged to explain how virulence and opportunistic infection apply to each other, and the correlation seems to be stronger when the number of ways an infection can become more virulent if the infection is opportunistic. Finally, pathogenetic capacity is directly impacted by virulence factors.
A key factor to consider when discussing opportunistic infection is looking at how the human body’s greatest weapon, its immune system, can also become its greatest enemy. Without going too far into Immunology, the propensity of T-cells and B-cells to overperform can sometimes exceed their inability to perform in immunocompromised patients. This happens when a foreign pathogen, organism, or even chemical imbalance is detected and attacked by immunoglobulins from the lymphatic system. Often, too many Immunofactors, or IF’s are released, causing not only the destruction of the foreign objects or chemicals, but also the host tissue. This may seem like a digression, but it is important to this paper because when the immune system malfunctions and impacts healthy human tissue, a major pathway for opportunistic infections are introduced.
Other virulence factors include adhesins, proteins that attach to the cell wall; colonization, the ability of potential pathogens to sustain themselves in or on different parts of the human body; invasion, usually through cotransport via cell membranes; Immune response inhibitors, a factor usually exploited more by viruses, in which which immune cells’ receptors are blocked by a pathogen, rendering them useless; toxins, both endotoxins and exotoxins, substances like PVL in S. Aureus that destroy cells is the subject of its own branch of immunologic research; finally, there are siderophores, which starve cells of their iron, providing bacteria with additional resources (Wilson, Schurr, et al., 2002).
All of these virulence factors help to determine a microbes pathogenesis. It would seem, then, since we have all this information, we should be able to continue development of newer and more strain specific bacteria. The truth seems to be, however, that Big pharma is becoming increasingly unwilling to fund research as fewer and fewer trials have yielded positive results. This is a problem that is still being caused by the clinical and hospital dependence on broad spectrum antibiotics. Like Triclosan in antibacterial soap, as they continue to wipe out susceptible bacteria, they pave the way for resistant bacteria.
Additionally, most antibiotics, up until this century, have been focused on infiltrating the pathogen’s cell wall. The problem with this is that many types of bacteria are gram-negative, meaning they have a cell wall made up of a double membrane. Few antibiotics can penetrate this double membrane. Also, when a cell wall is destroyed with nothing else backing it up, toxins can be released into extracellular fluid.
The good news is that new and exciting treatments are still coming or have come, but are still too expensive to be practical. A better understanding of molecular genetics and the role of newly discovered microRNA’s are helping researchers pinpoint new potential treatments, at rather cheap costs. Research into the activity of siderophores has a lot of potential, it is just now being looked at seriously (Lutz, 2016). Bacteriophage therapy is reaching Phase 3 clinical trials in the US. These are viruses whose “drills” are too short to penetrate human cells, but can easily attack gram-negative bacteria. In most British hospitals, surgical rooms are now being completely lined with nano-silver paint. Nano-silver is bacteriocidal, meaning that toxins are destroyed along with the rest of the bacteria.
We are right back to where we were one hundred years ago, let’s face it. The overuse and abuse of antibiotics has put us in that position faster than anticipated, but it was bound to happen with the linear approaches to therapy that were being explored. Now the world of microbiology and pathogenic treatment is more enticing than ever before. A new era of medicine awaits.
References
Brown, S., Cornforth, D. and Mideo, N. (2012). “Evolution of Virulence in Opportunistic
Pathogens: Generalism, Plasticity and Control. Trends in Microbiology. 20(7):336-342
Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491314/#__ffn_
sectitle.
Lutz, D. (2016). “Two-for-one bacterial virulence factor revealed.” Washington University
of Saint Louis. Retrieved from https://source.wustl.edu/2016/01/two-one-bacterial-
virulence-factor-revealed/.
Wilson, J., Schurr, M., et al. (2002). “Mechanisms of bacterial pathogenicity.” Postgraduate
Medical Journal. 78:216-224. Retrieved from http://m.pmj.bmj.com/content/78/918/
216.full.
