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Friday, 21 October 2016 14:03

The Nose Knows Beneficial Bacteria

Written by Lindsey Bomar

Bomar2016 1012 ASM Blog Fig1Figure 1. The nostrils are the entrance to the human nasal passages and open onto the skin-covered surface of the nasal vestibule. Moving posterior is the nasal cavity, a mucosal surface, followed by the nasopharynx (the top of the back of the throat). (Image: modified from Brugger SD, Bomar L, Lemon KP (2016) Commensal–Pathogen Interactions along the Human Nasal Passages. PLoS Pathog 12(7): e1005633. doi:10.1371/journal.ppat.1005633) Illustration by Virge Kask (University of Connecticut).

A complex bacterial community lives along our nasal passages (Fig. 1). However, scientists know relatively little about the function of our nose bacteria, including how beneficial members of our nasal microbiota might help keep us healthy. To date, nasal microbiome research has focused mostly on answering the “who’s there?” question, cataloging the different types of bacteria residing within the noses of children and adults. These bacterial community surveys, which typically employ high-throughput sequencing of a small region of the 16S rRNA gene, have revealed that pediatric nasal microbiota are often dominated by the phyla Firmicutes, Bacteroidetes and Proteobacteria but contain fewer Actinobacteria (mostly of the genera Corynebacterium and Propionibacterium). In contrast, the phyla Actinobacteria (mostly Propionibacterium and Corynebacterium) and Firmicutes (mostly Staphylococcus) dominate adult nasal microbiota. Streptococcus pneumoniae and Staphylococcus aureus are also commonly found in pediatric and adult nasal passages, respectively.

S. pneumoniae and S. aureus can be considered pathobionts (bacteria that can be benign or pathogenic). Most human interactions with S. pneumoniae and S. aureus are harmless (they live in the noses of many healthy individuals as commensals). However, these bacteria can cause severe disease. It is not well understood why these pathobionts colonize the nasal passages of some individuals but not others, nor are what causes a pathobiont to shift from a commensal to pathogenic state. However, colonization is a prerequisite for infection and understanding how these pathobionts colonize our nose drives many microbiologists’ interest in human nasal microbiota.

Bomar2016 1012 ASM Blog Fig2Figure 2. C. accolens inhibits S. pneumoniae growth on medium containing the triacylglycerol, triolein. (Image: modified from Bomar L, Brugger SD, Yost BH, Davies SS, Lemon KP. 2016. Corynebacterium accolens releases antipneumococcal free fatty acids from human nostril and skin surface triacylglycerols. mBio 7(1):e01725-15. doi:10.1128/mBio.01725-15.)

Some scientists hypothesize that interactions between pathobionts and other nasal bacteria are an important aspect of pathobiont colonization. Thus, in addition to defining composition, scientists use bacterial surveys to look for shifts in the bacterial population in the presence or absence of S. pneumoniae (pneumococcus) or S. aureus, or during a state of health versus disease. This wealth of information is then  mined for clues as to which bacteria might be interacting with each other. These clues are often in the form of positive or negative correlations of relative bacterial abundances in relation to a specific bacterium or disease. For example, if two genera co-occur, one could hypothesize they interact synergistically. Conversely, an observation that two bacterial groups are negatively correlated with one another could indicate a potential antagonistic interaction. Researchers can then test predicted bacterial interactions in the laboratory. This approach enables the human nasal microbiota field to start answering questions that get at function, such as “What are these nasal bacteria doing?” “How do these bacteria interact?” and “What impact do these interactions have on human health?”

Triolein, a representative human skin surface triacylglycerol. Triolein has a glycerol backbone and three oleic acid moieties, one of which is highlighted in blue. Figure 3. Triolein, a representative human skin surface triacylglycerol. Triolein has a glycerol backbone and three oleic acid moieties, one of which is highlighted in blue. (Image: modified from Bomar L, Brugger SD, Yost BH, Davies SS, Lemon KP. 2016. Corynebacterium accolens releases antipneumococcal free fatty acids from human nostril and skin surface triacylglycerols. mBio 7(1):e01725-15. doi:10.1128/mBio.01725-15.)

Our research group used this approach in a recent study aimed at understanding how benign human nasal bacteria might protect against S. pneumoniae. We first asked, “How does the bacterial community composition in the pediatric nasopharynx differ between children who are colonized by S. pneumoniae and those who are free of pneumococcal colonization?” We found that children who lacked S. pneumoniae nasopharyngeal colonization had an overrepresentation of Corynebacterium spp., a group of bacteria that includes mostly benign species. Based on this negative correlation, we hypothesized that antagonism exists between S. pneumoniae and, at least some, Corynebacterium spp. We designed an in vitro cocultivation experiment to test how these bacteria might interact. In this assay, the two types of bacteria are grown in close proximity to one another, and are monitored for evidence of growth inhibition mediated by a diffusible substance. Using this assay we discovered that Corynebacterium accolens, a benign member of human nasal and skin microbiota, inhibits pneumococcal growth (Fig 2) on medium supplemented with triolein. Triolein is a representative human skin triacylglycerol, similar to the triacylglycerols found on skin lining the nostrils. The C. accolens lipase LipS1 hydrolyzes triolein (Fig 3), releasing oleic acid, a fatty acid that inhibits pneumococcal growth. Based on this study, we predict one function of C. accolens is to inhibit pneumococcal growth in the human nasal passages through the catabolism of host-derived lipids. Several other research groups have used a similar approach of mining bacterial community composition datasets to study bacterial interactions along the human nasal passages. Some of these studies are outlined in this recent review article, and more recent studies have been, and are being, published in this expanding area of microbiome research.

How can we use knowledge gleaned from human microbiome studies, like the one described above, to manage our microbiota in a way that helps prevent disease? This is a common and critical question. Ultimately, one goal of bacterial interaction studies is to identify compounds and/or bacterial strains that can be developed as prebiotics and as probiotics, respectively, to prevent pathogens from colonizing us or treat infection. For example, the mechanism underlying the C. accolens-S. pneumoniae interaction paves the way for future testing of triolein as a prebiotic compound, which we predict will increase the Corynebacterium population, thus shaping the microbiota in a manner that is protective against pneumococcal colonization. In addition, future research could test C. accolens directly as a probiotic organism, since C. accolens has rarely been implicated as causing infection.

Human nasal microbiome research is in an exciting phase. Existing bacterial community composition datasets are a great foundation for designing mechanistic studies aimed at determining how bacterial communities are shaped. In addition, bacterial interaction studies can identify new antibiotics or other small molecules, which alter the growth or behavior of bacterial pathogens. These compounds are promising candidates for development as novel therapies for preventing or treating bacterial infections. Knowing the nose can get us one step closer to the long-term goal of managing our microbiota to benefit both personal and public health.

Lindsey Bomar

Lindsey Bomar is a postdoctoral research fellow in Katherine Lemon's laboratory at the Forsyth Institute in Cambridge, Massachusetts. Lindsey is interested in studying the function of host-associated microbial communities, how such communities are shaped by host-microbe and microbe-microbe interactions and the impact of microbial communities on the host. To learn more about the research on bacterial interactions in the human nasal passages, check out the Lemon Lab webpage.



Last modified on Friday, 21 October 2016 15:39

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