Once upon a time, the Group A streptococci were decent bacterial pathogens. Every now and then, they would wind up in a nice comfortable set of human lungs and take the opportunity to cause a little pneumonia. Sometimes a few cells would get really lucky and find their way into the blood, causing meningitis or sepsis. Then, in the 1980s, the Group A streps suddenly developed the disconcerting ability to cause a disease known as necrotizing fasciitis. Commonly called the “flesh-eating infection,” necrotizing fasciitis rapidly and horrifically destroys soft tissue. A recent study published by the National Academy of Sciences was able to shed light on how and when this mediocre pathogen became a real monster.
The most common way of getting necrotizing fasciitis, according to the CDC’s informational webpage “is when the bacteria enter the body through a break in the skin, like a cut, scrape, burn, insect bite or puncture wound.”
Once under the skin, the bacteria replicate and spread, targeting a connective tissue called “fascia.” As a National Geographic article covering the recent study puts it, “The bacteria infect layers of membranes and connective tissue around muscle, nerves, fat, and blood vessels. The toxins made by the bacteria destroy the tissue they infect, causing it to die.”
The infection progresses quickly and in just hours can destroy pounds of tissue.
According to the CDC article, the only solutions are IV antibiotics and, often, amputation of the infected tissue.
The Group A strep study published in the Proceedings of the National Academy of Sciences was a massive examination of bacterial population genetics. The research group sequenced 3,615 different genomes from Group A streptococci. The researchers were then able to compare the genomes from different points in time and deduce the timing and the mechanisms underlying the Group A’s sudden change.
In the paper, the researchers claim that the Group A streptococci gained the ability to cause necrotizing fasciitis in four steps. Each of these steps represented the gain of genes, or mutations that altered existing gene products.
The first step was infection of a Group A strep cell by a bacterial virus called a phage. Phages usually destroy their host cells, but in some cases they integrate into the bacterial genome. Once they integrate, those genes can be expressed by the cell. In this case, the phage was carrying a gene that coded for an enzyme called a “DNAase.” The DNAase molecule was successfully expressed by the Group A step and increased the capacity of the pathogen to cause disease.
The second step was another phage-mediated gene transfer. This time, the phage conferred the necessary genes to produce a toxin variant called SpeA1. Step three of the pathogen’s transformation was a mutation that switched a single letter in the SpeA1 gene, slightly altering the toxin. The final result was dubbed SpeA2.
The final step in the Group A’s transformation was the gain of a chromosomal region that encoded two more molecules: NAD+-glycohydrolase and streptolysin O. These genes were gained by horizontal gene transfer from other bacterial species.
All told, the Group A streptococci gained two new enzymes and two new toxins. These four molecules, in turn, gave the Group A streptococci the capacity to ravage soft tissue. The final gene transfer, according to the National Academy of Sciences’ paper, happened sometime in the early 80’s: this timing coincided with a large global increase in cases of necrotizing fasciitis.
This study is an excellent demonstration of precisely how devious microbial pathogens are capable of being. The Group A streptococci, by virtue of their ability to take in and use foreign DNA, evolved into very dangerous pathogens in an evolutionary millisecond. Such extreme adaptability is a hallmark of microbes, and stands as testament to how important it truly is to carefully monitor our microscopic adversaries.
