Mutation of pathogens
Mutation of pathogens refers to changes in the genetic material of microorganisms, such as bacteria and viruses, that can enhance their ability to cause disease. These mutations can occur through various mechanisms, including nucleotide substitutions, insertions, or deletions that alter protein function. For instance, missense mutations replace one amino acid in a protein, while nonsense mutations lead to truncated proteins. Pathogens can also undergo horizontal gene transfer, allowing them to acquire genes, such as those conferring antibiotic resistance, from other bacteria. High mutation rates can lead to significant public health concerns, particularly with viruses like influenza, which mutate frequently and can cause widespread outbreaks and pandemics.
The emergence of new infectious diseases, often influenced by mutations, has been noted since the 1970s. For example, certain strains of E. coli can mutate from harmless to harmful due to acquired toxin genes. Notably, pathogens like SARS-CoV-2 have undergone mutations that increased their transmissibility, prompting global health responses and advancements in treatment and prevention strategies. Modern research leverages genomic sequencing and artificial intelligence to monitor these mutations, aiming to combat the evolving threat of infectious diseases. Understanding pathogen mutation is crucial for developing effective vaccines and treatments to mitigate their impact on public health.
Mutation of pathogens
Definition
A mutation is any change in genetic material that is passed from one generation to another. If the mutation occurs in a disease-causing (pathogenic) microorganism, such as a bacterium of virus (bacteriophage), and if the change enhances the pathogenicity of that bacterium or virus, then the mutation can be problematic.
Mutation Types and Mechanisms
Mutations have a genetic basis. A change in the sequence of nucleotides, the building blocks of a gene, can affect the production (more or less product produced) or the structure of the encoded product. An alteration in the sequence of nucleotides, but not in the number of nucleotides, is a nucleotide substitution.
Two types of nucleotide substitution mutations exist. A missense mutation is a change in only one nucleotide, which results in the substitution of one amino acid for another in the protein product. A nonsense mutation is also a single nucleotide change, but the alteration halts the transcription of the gene, which results in a shortened, dysfunctional protein product.
Other mutations do change the number of nucleotides. An increase is caused by the insertion of more nucleotides and is termed an “insertion mutation.” Accordingly, a “deletion mutation” involves the removal of nucleotides. Removing or adding nucleotides produces a frameshift in which the normal sequence with which the genetic material is interpreted is altered. The alteration causes the gene to code for a different sequence of amino acids in the protein product than would normally be produced. The result is a protein that functions differently (better or worse, depending on the mutation) or not all, as compared to the normally encoded version.
Gene transfer between bacteria can occur even between species that are unrelated. This horizontal gene transfer occurs in nature. It can be important in infectious disease, for example, in the acquisition of a gene that determines antibiotic resistance.
The transfer of genes between bacteria can occur in several ways. A gene in the genome of the donor microbe can be transferred to the recipient bacterium through a tube that transiently connects the two cells. The recipient is then able to express the encoded product. Bacterial genes also can reside on more readily mobile structures called plasmids. Plasmids are more easily transferable between bacteria.
Another genetic mechanism of bacterial evolution involves bacteriophages, viruses that specifically infect a particular type of bacteria (for example, various types of coliphages infect various strains of Escherichia coli). When a bacteriophage infects a bacterium, the viral genetic material can insert into the host’s genetic material. When the viral material is excised, some of the host’s genetic material can be removed as well, to become part of the genome of the bacteriophage. A subsequent infection of another bacterium can transfer genes from the first bacterium to the second bacterial host. If the new gene confers an advantage to the second bacterium, it will be retained and passed on to subsequent generations of bacteria.
Pathogens and Mutation
Mutations are an important driver of the development of pathogens. A good example is the influenza virus. Three types of orthomyxoviruses cause illness in humans and animals: types A, B, and C. Type A influenza has produced several epidemics, in which large numbers of people become infected during a short period of time, and pandemics, in which the illness can extend globally. The influenza epidemic of 1918 killed more people than the just-ended World War I. Mutated versions of this virus were responsible for epidemics that occurred in 1957, 1968, and 1977.
Type A viruses infect both humans and animals and usually originate in the Far East, where a large population of ducks and swine incubate the virus and pass it to humans. The passage of virus in the duck or swine populations promotes the formation of mutants. While some of the mutants will confer no advantage, others will. From these, new infections can emerge.
In 1997, a new strain of influenza A jumped from the poultry population in Hong Kong to the human population. The strain of virus, which was dubbed H5N1 (and was dubbed avian influenza), produces a severe and sometimes fatal infection in humans. In 2004, the avian influenza A(H5N1) began to display signs of acquiring the genetic ability to pass directly from person to person. In 2006, only a few such cases had been reported, but thereafter, the disease gained strength. According to figures from the World Health Organization, by the end of 2010, 510 human cases had been officially recorded, with 303 of these cases resulting in death (a death rate of 59 percent). Experts feared that further mutations of the H5N1 virus would increase the efficiency of bird-to-human transmission, enhance the ease of human-to-human transmission, and increase the already high death rate. Experts feared the result could be a pandemic that dwarfed the casualties of the 1918 epidemic.
By late 2024, 904 cases had occurred across twenty-four countries, of which, over 460 were fatal. From 2013 to 2024, 1,568 cases of avian influenza A(H7N9), and from 2015 to 2024, ninety-four avian influenza A(H9N2) were reported to the World Health Organization. In January 2024, two cases of avian influenza A(H10N3) had been reported to the WHO.
Because of the small amount of ribonucleic acid (RNA) genetic material within influenza viruses, mutation of the genetic material is very common. The result of this frequent mutation is that each flu virus is different, and people who have become immune to one variety of influenza virus are not necessarily immune to other influenza viruses. The ability to mutate frequently, therefore, allows these viruses to cause frequent outbreaks. Annual flu shots are recommended because protection conferred by the vaccine from the previous year is not guaranteed to be effective again.
Emerging Infections
Pathogen mutations also play a role in emerging infectious diseases, those human diseases of microbial origin that have increased in prevalence since the 1970s or have threatened to become more widespread.
Emergence may be genuine. In this case, a mutation has occurred that changes the character of a once-innocuous microbe. An example is E. coli O157:H7, which acquired a gene that encodes a destructive toxin. Without the gene, the organism is a normal (commensal) resident of the intestinal tract, where it may even confer some benefits to the host. With the toxin gene, the bacterium can cause a serious disease that can permanently damage the kidneys and can be lethal. Other mutation-related changes can make bacteria or viruses more capable of infecting a host, better able to survive in the external environment (and better able to be transferred from person-to-person), or resistant to antibacterial agents.
In the era of rapid worldwide travel, diseases can quickly spread globally. This was exemplified by the 2002 to 2004 outbreak of severe acute respiratory syndrome (SARS), which spread within days from Taiwan to North America and across the globe, causing 774 deaths and 8,000 infections in thirty countries. This incident underscored how quickly a mutated organism can spread worldwide. An outbreak that occurs in a remote area of the globe is no guarantee that people far away from the site of the original infection are safe.
The coronavirus pathogen that caused the COVID-19 pandemic in the early 2020s, SARS-CoV-2, underwent several notable mutations, resulting in pathogens like the SARS-CoV-2 D614G mutation on the S-protein, increasing the pathogen’s transmissibility. Many of the most prominent and commonly known mutations of SARS-CoV-2 were named Alpha, Beta, Delta, and Omicron. These emerging pathogens presented significant challenges, which, in turn, prompted breakthroughs in scientific understanding of pathogenic transmissibility and resistance to treatment. As scientists better understood the underlying mechanisms facilitating these mutations, they were able to develop diagnostic tools, treatments, and vaccines to limit the global spread of the pandemic and lower death rates. Modern research in emerging infections utilizes genomic sequencing and artificial intelligence predictive algorithms to monitor, address, and prevent mutations of dangerous pathogens.
Impact
The ability of disease-causing organisms (pathogens) to change (mutate) is vital to their ability to cause disease. An important example is bacterial antibiotic resistance. Some pathogenic bacteria have developed resistance to nearly all known antibiotics and, for one species, all antibiotics.
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