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The pathogenic mechanism of Ans strain: How do two plasmids determine its lethality?
The Ames strain is one of 89 known strains of Bacillus anthracis. This strain was first isolated in 1981 from a sick 14-month-old calf in Sarita, Texas. After a series of tests and misinformation, the strain was eventually sent to the U.S. Army Research Institute of Infectious Diseases (USAMRIID). Widespread attention to the Ances strain began following the 2001 anthrax attacks, when seven letters containing the strain were sent to various media outlets and U.S. senators.
The reason why the Ansi strain is used by the United States to develop vaccines and test their effectiveness is because of its extremely high pathogenicity.
The pathogenicity of the Ans strain mainly comes from two specific virulence plasmids, namely pXO1 and pXO2. These two plasmids showed stronger pathogenicity than other strains among Ans strains. pXO2 encodes a poly-D-glutamic acid capsule that resists phagocytosis, allowing B. anthracis to evade the host immune system, while pXO1 encodes three toxin proteins: edema factor (EF), lethal factor (LF), and protective antigen (PA).
When bacteria lack either pXO1 or pXO2, they are considered attenuated, meaning they cannot cause serious infections.
Differences in pathogenicity between strains can be explained by the presence or absence of plasmids. For example, even strains with only Ames pXO2 plasmid are still highly pathogenic to mice, indicating that pXO2 contributes significantly to pathogenicity. In contrast, the Sterne strain is avirulent and cannot cause major disease in animals or humans.
Regarding antibiotic resistance, the Anthrax strain is susceptible to CDC-recommended treatment regimens, similar to most other anthrax strains. Although Sterne strains possess functional β-lactamases, gene expression is often insufficient to confer resistance. According to the dosage standards published in the Clinical Laboratory Standards Institute M45 document, Ciprofloxacin is the recommended drug for the treatment of respiratory anthrax. Recent studies have shown that gatifloxacin, another new fluoroquinolone antibiotic, can improve the survival rate of mice susceptible to the Ansi strain.
Although the PA vaccine is not as protective as the live spore vaccine, it is still one of the options currently being developed.
Currently, vaccine development against B. anthracis mainly relies on attenuated strains, especially strains whose virulence plasmids have been removed. Sterne strains naturally lack pXO2 and therefore can be used safely to mount an immune response. Existing vaccines include live spore vaccines designed specifically for animals, but they are dangerous to humans, so vaccines based on protective antigens are also being explored.
Currently, the only licensed human anthrax vaccine in the United States, Anthrax vaccine adsorbed (AVA), is based on protective antigens, but its effectiveness against the Ames strain varies depending on animal models. This inconsistent result highlights the need for comprehensive studies in multiple model organisms to test vaccine efficacy in humans. Researchers are also currently actively looking for ways to inactivate anthrax spores with formaldehyde and other substances to provide humans with new alternatives to live spores and PA vaccines.
Identification of nucleotide polymorphisms (SNPs) of Ansinus strains can help track the outbreak.
Six highly specific SNPs have been identified for the Anse strain, making diagnostic testing possible in the flora. These SNPs can not only distinguish the Ames strain from 88 other species of Bacillus anthracis, but also provide important information for epidemiological studies. The low genetic change rate of the Ans strain further ensures its stability as a diagnostic marker. Using a combination of these SNPs and real-time PCR, the researchers were able to confirm or rule out thousands of samples as being of the Andersen strain.
The stability of the Ans strain and its potential bioweapons risk make us think again: What measures should humans take to strengthen defense when facing the threat of such deadly pathogens?
