Pathogenic microbiome bacteria change shape to adapt to nasopharyngeal environment

Microbiome bacteria are highly adapted to their surroundings.  They face constant pressure from the immune system as well as other bacteria, fungi, and even small molecules such as antibiotics.  It should come as no surprise then, that many of these bacteria have undergone major evolutionary adaptations to survive the human body.  Apparently, as discovered by French group and published in PLoS Genetics, one common strategy amongst many different bacteria is a shift from rod shaped to spherical shaped (coccoid). 

The scientists investigated the genealogy of bacteria for the family Neisseriaceae, which have species with a high diversity of shapes, including some members from the human nasal microbiome, like Neisseria meningitidis that are spherical.  In tracing the histories of this bug they noted that many other bacterial species showed a similar tendency, that is they converted from rod to coccoid after entering the nose.  The researchers were even able to track down the simple genetic mutations responsible, and they noted that this mutation to coccoid conferred many fitness advantages over the rod shape.  For example, the coccus shape has a higher surface to volume ratio than the rod, so that the host immune system has less surface to detect, without sacrificing as much volume in the cell.

It is interesting to look into the evolutionary developments of microbiome bacteria, because they shed light on the shared strategies of these commensals in coexisting with their host.  These adaptations actually differentiate the commensals from the non-commensals which are potentially pathogenic, because foreign bacteria don’t stand a chance of evading our immune system, especially compared to bacteria that have evolved with us throughout the entirety of human history. 

Sometimes-pathogenic Neisseria are constantly invoking immune response in humans

Fluorescent antibody stain of Neisseria gonorrhoeae.

Bacteria from the genus Neisseria exist as normal commensals in greater than 95% of adults.  That being said, two strains, Neisseria meningitides (a cause of bacterial meningitis) and Neisseria gonorrhoeae (the cause of gonorrhea),are known pathogens, although these too can often asymptomatic.  A new study published last week in Science suggests that although asymptomatic, Neisseria may always be inducing an autoimmune response, via a metabolite they are constantly producing and releasing into the environment. 

Using genetic approaches, scientists from the University of Toronto identified the inflammation-inducing metabolite as heptose-1,7-bisphosphate (HBP), which prior to the study had not been implicated as causing an immune response.  To prove its effect, the researchers injected the metabolite into mice and showed that these mice displayed inflammation almost immediately.  The scientists recognized that this metabolite is actually produced by many bacteria, and wondered if these others were causing harm as well.  Using mouse studies though, they demonstrated that other bacteria do not release it from their cells into the environment, so these bacteria only induce a response when they are lysed.  Thus far only Neisseria have been shown to produce and release this metabolite, which is important because it means as long as they are growing they are constantly producing an immune response. 

The scientists also discovered the immune pathway by which HMP triggers a response: the TRAF-interacting protein with forkhead-associated domain (TIFA).  Interestingly, it has been known for many years that infection with N. meningitidis or N. gonorrhoeae increases HIV shedding and transmission, but the reason was still a mystery.  The scientists figured out this connection when they recognized that HIV actually use the TIFA pathway to reproduce.  They observed that these bacteria invoke the TIFA response via HBP, which gives the HIV the proper cells it needs to replicate.

Given what we know about the effects of chronic inflammation and its effects on many diseases these findings could be very important.  Perhaps there is no such thing as a nonpathogenic Neisseria, and its existence in ‘healthy’ guts may not be so healthy after all.

The placental microbiome

Microbiome populations have been well-characterized in many distinct body-sites.  Interestingly, there is a lack of knowledge in the microbiome of the placenta, an environment that was long thought to be sterile.  Investigating the placenta is important toward understanding the microbiome in human development, especially in light of previous evidence demonstrating that human microbiota populations fluctuate extensively in the first year(s) of life.  The placenta is the cradle of life for fetal development, leading researchers from Baylor School of Medicine to study the microbiome of this tissue.  Placenta samples were collected and analyzed to characterize the placenta microbiome, and explore links to fetal development and microbiome compositions. 

320 placenta specimens were collected, and PCR was used to characterize bacterial populations.  The Meta genome sequencing revealed that the placenta microbiome harbored unique abundances in specific bacteria compared to other body sites.  E. coli in particular had the highest species abundance.  Interestingly, the microbiota populations were most similar to the oral microbiome.  Species such as Prevotella tannerae and Neisseria, known to populate the mouth, were also abundantly present in the placenta.  Further analysis confirmed that the placenta bacteria were indeed most similar to bacteria specifically found in the tongue, tonsils, and gingival plaques. 

The researchers also demonstrated an association between placental microbiome composition and healthy births or births with complications.  Specifically, a significant association was shown between distinct placental microbiome populations and pre-term birth.  Taxa such as Durkholderia were shown to be enriched in the placentas of those who delivered their infants preterm, whereas Paenibacillus was abundant in normal terms placental specimens. 

This study reveals a couple very interesting associations between cross-site microbiome similarities and disruptions in compositions that appeared to be linked to preterm birth.  Although not definitive evidence, these findings could lead to some important research in the future.  There were a few confounding elements to this study, such as other body site samples occurred in non-pregnant subjects, or the fact that the mass of the placental microbiota was particularly low.  However, these findings certainly raise awareness of the uniqueness of the placental microbiome, and what this means in terms of the microbiome entering the developing fetus.  It will be interesting to see what further research can reveal about this relationship. 

Asthma, COPD, and the Microbiome

Asthma and chronic obstructive pulmonary disease (COPD) are both illnesses that are caused by chronic inflammation of the respiratory tract, and recent research suggests that the microbiota of the lower respiratory tract may influence the development of these two diseases.  The upper respiratory tract, though, remained unstudied, until a new article was recently published in PLoS ONE.  This article characterized the microbiome of the oropharynx (in the upper respiratory tract) to discover the association between these problems and the microbiome.

Samples were swabbed from the oropharynx of patients who were recently diagnosed with asthma and COPD, as well as from a healthy control group.  Researchers performed 16S rRNA gene sequencing of the bacteria collected from the patients, in order to determine which bacteria were present. They found that there are few differences in microbiome diversity between asthma and COPD patients, however there was a prevalent presence of the bacteria Lactobacillus (phylum Firmicutes) and Pseudomonas (phylum Proteobacteria) in both, which were identified in only very small amounts in healthy patients. On the contrary, the upper respiratory tract of healthy individuals was found to be dominated by Streptococcus, Veillonella, Prevotella, and Neisseria, from the phylum Bacteroidetes, compared to individuals with asthma and COPD.

This study showed distinct differences in the microbiomes of diseased and healthy individuals.  The researchers also note that the low abundance of Neisseria they observed in this study has also been seen in studies of smokers, meaning that this bacteria may be important to respiratory health.  Further work is still needed, though, to determine if the bacteria identified in this study are contributing to the diseased individuals.  Even if they are not, they could still potentially be used in diagnosis.