Question 1 A microbial pathogen can be defined as: "An organism capable of causing disease". How good is this definition? (ver 2)

A microbial pathogen can be defined as: "An organism capable of causing disease". How good is this definition?

The word "pathogen" is derived from a greek context confering meaning of "suffering" and "to give birth to". Currently this word refers to a biological agent that causes diseases or illness to its host. Microbial lifeforms constitute the most abundant and richly diverse group of organisms that inhabit Earth. They have adapted to environments of all extreemes, evolved in complexity and capacity to evolve. They play a key role in many aspects of life for other organisms, and are almost certainly capable of causing disease.

Various bacterial, viral, fungal, helminth and protozoan organisms have been linked to causing disease in humans. The discovery of these microbial lifeforms was first made when microscopes were invented by Robert Hooke. However for a while, many people continued to believe that human disease and suffering was considered punishment by their gods for sin and disobediance. This continued even throughout periods where disease such as the 'plague' was among the most dreaded and feared phenomenon. Finally Louis Pasteur developed the germ theory of disease, a theory that proposes that microorganisms are the cause of many diseases, and experiments conducted by Robert Koch solidified this theory in the development of Koch's Postulates.
This definition of a microbial pathogen is currently challenged by today's current understanding of molecular biology, the bodies immune system and the mechanism of a microbial infection. On what grounds does this argument hold true? What are the flaws in this argument, and can it be improved?

Most microbes found on the human body have evolved in co-evolution as commensal organisms. Microbes found on our skin create a balanced ecology forming another barrier against unwanted colonisation. Microbes found in the gut may play a similar role but may also assist in digestion and the and absorption of macro and micro-nutrients facilitating for better health through immunological protection and nutrition. However these bacteria may also present a challenge to the body when the host is immunocompromised, the ecological balance is upset or the bacteria have access to a new compartments in the body. For this reason these relatively harmless commensal microbial organisms become opportunistic pathogens. Since bacteria are the most abundant microbe that inhabits our bodies they are most frequently involved in opportunistic infections. Staphylococcus epidermidis is a relatively innocuous bacteria that lives on the epidermal layers of the skin presenting no harm to the individual. However they are commonly implicated in post-surgical complications whereby catheters have been inserted in the skin and these bacteria have a free ride into the body; subverting the need to penetrate the skin by its own mechanisms. Once in the body, the bacteria can cause many a stapylococcal infection that can lead to significant fever and potentially death.
One distinct difference among commensal microbes, opportunist microbes, and pathogens is that pathogens have evolved the genetic ability to breach the cellular and anatomic barriers that ordinarily restrict other microorganisms (Stanley Falkow). One particular bacteria of the gut; Salmonella enterica may become particularly infectious when it acquires the ability to penetrate the gut walls. Servoar 'Typhi', have been the cause of the disease typhoid fever. The organism can be transmitted by the fecal-oral route—it is excreted by humans in feces and may be transmitted by contaminated water, food, or by person-to-person contact (with inadequate attention to personal hygiene).

Viruses are especially adapted at penetrating the host, replicating and spreading throughout a host. There are countless examples including HIV, a virus renoun for its ability to reduce the immune systems' capabilities. HIV is an RNA retrovirus that has a high affinity for the CD4 antigens of T lymphocytes and antigen presentinc cells such as dedrocytes and macrophages via the gp120 protein. Once attached, the virus penetrates these cells via a complex mechanism that manipulates the cells cytoskeletal structure and leads to insertion of the viral capsid protein contents. The DS RNA genome is unwound and integrated into the host cell's DNA via a process that requires RNA dependent reverse transcriptase. The virus may reassemble many times by expressing the newly integrated genome (consisting of gag and env genes). Viruses are obligate intracellular organisms, which make an immune response difficult because the reputable antigenic proteins are rarely able to be presented to the immune system. In addition, the HIV virus is highly mutagenic, with a rate of 3 x 10-5mutations per base per cycle generating up to 10^9 to 10^10 new virons each day. This is made possible by the recombinogenic properties of reverse transcriptase. And finally, since HIV affects the CD4 cell population, mounting an immune response is made increasingly difficult with where the entire population of effector T cells are reduced.
Fungal organisms are also capable of causing disease, however more associated with localised, topical infections rather than a systemic immune attack. Candiasis is a common fungal 'yeast' infection caused by Candida Albigans that may affect regions such as the mouth or vagina where conditions are moist, tissue is soft and the cells are columnar epithelial. These fungal infections may persist where the host is either immunocompromised, or the microflora of that region has been previously disrupted by the actions of antibiotics that kill off the protective commensal bacteria.
Finally protozoan life forms such as the Plasmodium spp. have been reputably associated with Malarial diseases. These species have established a complex lifestyle that features both the Anopheles mosquito and humans for survival and proliferation.
- Can go into detail about this;

In summary of the aforementioned microbes - essentially all are somewhat capable of causing disease; either because the host's natural defense mechanisms are in decline, or that they are specifically adapted pathogenic factors that enable them to penetrate the hosts defenses.

In spite of the previous evidence; there are many aspects that may challenge the hypothesis that microbial pathogens are specifically organisms that cause disease.
Prions are a new class of disease causing entities recently discovered. Prions by definition are 'infectious proteins', that have been linked to numerous neurodegenerative disorders such as bovine sporangiform encephalopathy (BSE), crautsford jakobs disease and curarie (in humans). Analytical studies have identified whole families of these 'misfolded' proteins that are observed in nature; two major isoforms exist - PrPC and PrPSC. In humans however, prions have also been attributed as highly carcinogenic proteins. Prions can also be transfered from host to host, as notes among canibals, where eating the brain and the spinal cord have been linked to such degenerative diseases. Recently, however studies have suggested that prions may simply play a part in the normal cell function of long term memory and even stem cell renewal. However prions cannot be considered organisms, while they may self-replicate, they do not specifcally evolve and adapt to their environment as would a typical organism.

Conclusions; Since the discovery of microbes and their association with pathogenesis numerous examples of viral, fungal, bacterial, protozoan and helminth infections have been recorded somehow associated with the onset and progression of disease. The definition of a microbial pathogen has been challenged over the years on religious and ethical principals, symbiotic theories and the paradox concerning the new discovery of infectious proteins. Despite these, the theory holds true, and remains robust.