Scientists at theStanford University School of Medicinehave revealed that formerly overlooked sites deep inside the nose may be reservoirs forStaphylococcus aureus, a major bacterial cause of disease.

The results of the study were published Dec. 11 inCell Host & Microbe.

The Stanford investigators further found an inverse relationship between the presence ofS. aureusat these sites and that of a different bacterial species,Corynebacterium pseudodiphtheriticum, suggesting that the two organisms compete with each other and thatC. pseudodiphtheriticum or some molecular product it excretes may prove useful in counteringS. aureusinfections.

About one-third of all people are persistentS. aureuscarriers, another third are occasional carriers and a remaining third dont seem to carryS. aureusat all, saidDavid Relman, MD, the Thomas C. and Joan M. Merigan Professor and a professor of medicine and of microbiology and immunology. Relman, who is also chief of the infectious disease section atVeterans Affairs Palo Alto Health Care System, was the studys senior author. The lead author was Miling Yan, PhD, a graduate student in Relmans lab at the time the experiments were performed.

The nose has been long known to be a primary reservoir ofS. aureus, Relman said. The bug also abounds on the skin, with a special affinity for the armpits and groin. The vast majority of the time, however, it does little or no harm. (If its doing any good, no one has figured out yet what that is, Relman added.)

But if the skin is compromised by, for example, a wound or a medical incision or catheter placement,S. aureuscan get into the bloodstream and cause serious and even life-threatening problems such as sepsis, pneumonia or infection of heart valves. Close to half of allS. aureusstrains are resistant to a family of antibiotics that includes methicillin. In 2011, more than 80,000 severe methicillin-resistantS. aureusinfections, as well as more than 11,000 related deaths, occurred in the United States alone, along with a much higher number of less-severe infections.

Not everyone who carriesS. aureusgets sick, Relman said. When theyre out walking the streets and otherwise healthy, attempts to rid them of theirS. aureusare not necessary, and even sometimes futile. But once a carrier enters a hospital with an underlying illness or a weakened immune system or a high likelihood of undergoing skin-penetrating procedures,S. aureuscarriage is a major liability.

Rigorous and somewhat tedious regimens for eliminatingS. aureusresiding on peoples skin or in their noses do exist, but its typically a matter of weeks or months before the bacteria repopulate those who are susceptible. The new study offers a possible reason why this is the case.

The scientists recruited 12 healthy subjects and brought them to a Stanford ear, nose and throat clinic run by study co-authorPeter Hwang, MD, professor of otolaryngology. Employing special instrumentation to allow them to guide tiny swabs to precise locations within the nose, they took samples from three specific areas. The first location and far and away the most well-studied because its much more accessible was the anterior naris, a relatively dry skin-like patch of tissue located near the nostril. The second was the middle meatus a warmer, wetter, mucus-producing fold found about midway up the nasal cavity. And the third was the sphenoethmoidal recess, situated deep within the cavity near the roof of the nose and, like the middle meatus, warm, wet and mucosal.

The researchers found that the presence or absence ofS. aureusat one nasal site typically correlated with its presence or absence at the other two. An implication: If a persons anterior naris is carrying the bacteria, the upper mucosal areas probably are, too. This could be why efforts to banishS. aureushave so often proved short-lived. Focusing efforts largely on the bacteria in the anterior naris, which current decolonization procedures do, leaves deeper reservoirs intact.

Relmans team learned three other things, as well. First, the relative abundance ofS. aureuswas inversely related to that of another bacterial species,C. pseudodiphtheriticum. When one was present at high levels, the other was present at low levels or absent. One of the studys co-authors, Sunje Pamp, PhD, a research associate in Relmans lab, put the two bacterial species on an agar plate to scrutinize this relationship further, and found thatC. pseudodiphtheriticumstrongly blocked the growth ofS. aureus.

The researchers suspect that somethingC. pseudodiphtheticumproduces and secretes perhaps a protein, or possibly a small molecule is responsible forS. aureus failure to thrive. If such a substance could be identified, Pamp said, it could provide clues to the development of new compounds to prevent or treatS. aureusinfections.

Second, the microbial communities in those patients who harborS. aureusdiffered in other ways from those in patients who dont. This could mean thatS. aureusalters its environment to make it more or less hospitable to various other microbes. Or it could mean that different microbial communities are more or less hospitable to colonization byS. aureus. If the latter is the case, it may be possible to predict, based on their resident nasal microbes, which patients are most likely to be at high risk of aS. aureusinfection even if theyre not currently carrying it and monitor and treat them accordingly. Those patients found to be at lower risk could be spared such procedures.

Third, in the middle meatus and the sphenoethmoidal recess the two deeper, wetter mucosal regions of the nose microbial communities were similar to each another, but quite distinct from the one inhabiting the more accessible and better-studied outer site, the anterior naris. This suggests that currently routine methods of sampling the nasal cavity for microbe-research purposes may be yielding skewed results.

Other study co-authors were graduate student Julia Fukuyama; otolaryngology resident Do-Yeon, MD; and statistics professorSusan Holmes, PhD. The study was funded by aNational Institutes of HealthPioneer Award (grant DP1OD000964), theDoris Duke Charitable Trustand the Thomas C. and Joan M. Merigan Endowment.

Information on Stanfords Department of Microbiology and Immunology and Department of Medicine, which also supported this work, is available athttp://microimmuno.stanford.eduandhttp://medicine.stanford.edu, respectively.