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.