Before the appearance of antibiotics, infection was rightly dreaded; once an infection began there was nothing medical science could do except to make the patient comfortable and hope. Fortunately, antibiotics have provided us at least a temporary edge in the struggle with infection, and we need all the assistance we can muster because our bodies not only house large numbers of bacteria like Staphylococcus aureus but also because the legions of bacteria have evolved a rich array of ways to penetrate the body's defenses. (Ribet and Cossart, 2015)
One of the most common bacteria, Staphylococcus aureus has the habits of Dr. Jekyll and Mr. Hyde. Ordinarily S. aureus is Mr. Hyde, found in the respiratory passages, the nose (only sometimes) and on the skin peacefully cohabiting with us so long as we are in good health. However, in its Dr. Jekyll manifestation it causes, among other things, skin infections (pimples, boils), sinusitis, and food poisoning. In its most Dr. Jekyll-like avatar, it is resistant to even the most potent antibiotics. This is the Methicillin resistant Staphloccocus aureus (MRSA) strain. MRSA is difficult to prevent and hard to cure; it kills about 11,000 people each year, often because of infections caught in hospitals.
The researchers began with the puzzle about why S. aureus is found in only about one out of every three noses. Why is it in some noses but not others?
As a habitat, the inside of the human nose is not a very inviting one. As one of the investigative team put it, "If I were a bacterium I wouldn't want to live there. There is nothing there, simply a salty liquid and a tiny amount of nutrients." (Kupferschmidt, 2016) Therefore, the investigators began their search with the ecology of the nose; what is in the nose's ecology that explains the presence (or non-presence) of S. aureus.
Even the spartan environment of the nose teems with bacteria, particularly with other species of Staphylococcus.
A painstaking screening of each of the 70 different nose-inhabiting species of Staphylococcus was conducted using a petri dish stocked with bacteria-friendly nutrients, S. aureus and one of the other Staph species.
One species, Staphylococcus lugdunensis, was found to inhibit the growth of S. aureus.
What property of the S. lugdunensis acted against the S. aureus?
The researchers soon identified a single molecule as its active agent. The molecule was somewhat different from the typical antibiotic agent in that it was larger and it also possessed a novel molecular structure (whose significance will be revealed later).
The team named the molecule Lugdunin and then set about synthesizing it in the laboratory. With the synthetic Lugdunin the team created an ointment and tested it by infecting the backs of lab mice with S. aureus and then treating one group with the Lugdunin ointment. The ointment was effective reducing or eradicating the infection on the treated mice.
In a significant finding, the Lugdunin ointment was also effective on the MRSA strains of S. aureus, infections that otherwise require special care. (Kupferschmidt, 2016) Other difficult-to-treat bacteria also succumbed to the Lugdunin molecule.
The initial findings may explain why S. aureus is present in only some noses; the presence of S. lugdunensis should be associated with the absence of S. aureus.
The researchers tested this proposition by conducting a survey of 187 hospital patients and found that those patients who had the lugdunensis species of Staphylococcus in their noses were six times less likely to have the problem-causing S. aureus in theirs. This part of their research suggests that a nasal spray containing the Lugdunin molecule could be used on patients who were at risk of S. aureus infection.
As for the molecule itself, Lugdunin possesses several properties that make its discovery promising at a time when our supply of effective antibiotics is being reduced.
Lugdunensis is a bactericide which means that it kills major pathogens that are otherwise resistant to antibiotics, and, in addition, in test tube experiments has shown that it does not appear to drive antibiotic resistance.
Finally, its method of inhibiting pathogens is interesting.
Its molecular structure enables it to inhibit the ability of bacteria to colonize body tissue. This is important because the first stage of a bacterial infection requires that the infectious bacteria colonize the cells that will be infected. Bacteria must attach themselves to the target cells; this is done in a variety of ways and is called "colonization." If the bacteria are not able to colonize the tissue, there will be no infection. Lugdunin thus blocks a key element in the development of infection.
Further study of the action of Lugdunin may reveal the as yet not understood mechanisms that inhibit bacterial colonization.
Last, the Lugdunin molecule is a rare example of an antibiotic that was developed in the human microbiome.
It may be that "our microbiome--the microbes that share our bodies--may be an untapped spring of new antibiotics" according to two microbiologists and antibiotic researchers at Northeastern University who were not involved in the Nature research. (Mole, 2016)
It is the nature of science that a finding in one area has ramifications in other, often unexpected, areas.
Thus Peer Bork raises a cautionary note that must be considered if Lugdunin lives up to its potential benefits for human patients (it has only so far been tested in animal models). Bork, a computational biologist notes that "Yes, it's a cool finding." But he warns that we must remember that the microbiome is a delicately balanced community of organisms as the result of millions of years of evolution. He continues, "It's more complex than goodies and baddies. Tinkering around might destroy long-evolved community relations." (Kupferschmidt, 2016)
Another complication is that S. lugdunensis is also associated with a variety of diseases so using it therapeutically will require care.
Kupferschmidt, Kai (2016). New antibiotic found in human nose. Science, July 27, 2016.
Mole, Beth (2016). Bacteria battling over boogers in your nose may have life-saving antibiotic properties. Ars Technica, (www.arstechnica.com) July 28, 2016.
Nowogrodzki, Anna (2016). The nose knows how to kill MRSA. Nature News, 27 July, 2016.
Ribet, David, Pascale Cossart (2015). How bacterial pathogens colonize their hosts and invade deeper tissues. Science Direct March 2015, Vol. 17(3) 173-183. doi:10.1016/j.micinf.2015.01.004.
Simon, Matt (2014). Fantastically Wrong: The Strange History of Using Organ-Shaped Plants to Treat Diseases. Wired, July 7, 2014.
Dr. John Holton
Dr. John Holton joined the S²TEM Centers SC in July of 2013, as a research associate with an emphasis on the STEM literature including state and local STEM plans from around the nation.