Friday, 26 August 2016 12:12

The inflammatory nature of a bad recycler

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Published in mBiosphere
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Neisseria gonorrhoeae TEM

Being a bad recycler implies creating more waste because items aren’t being reincorporated into the production chain. Plastic water bottles can be broken down and turned into new plastic bottles, gardening gloves, or fleece – any of which means less oil needs to be harvested and refined to the polymers that constitute these different items. Bacteria, in general, also tend to be very good recyclers. The energy it takes to reuse a compound is generally less than to build the molecular structure from scratch.

An example of bacteria recycling efficiency comes with the cell wall, made of peptidoglycan, which must be remodeled for cell growth and division. Rather than cleave and release peptidoglycan polymers, many bacteria recycle the fragments freed during remodeling to incorporate for new wall synthesis. In Neisseria species, the majority of the freed peptidoglycan fragments are transported into the cytoplasm through the AmpG permease. However, not all Neisseria are equally proficient at this peptidoglycan recycling, and new research published in the Journal of Bacteriology demonstrates that N. gonorrhoeae is the least efficient recycler among related Neisseria species, with an inflammatory effect.

Authors Jia Mun (Elizabeth) Chan and Joseph Dillard investigated different human-associated species of Neisseria. Most Neisseria are commensals that very rarely cause disease, while two – N. gonorrhoeae and N. meningiditis – are associated with disease. These species release peptidoglycan fragments that act as pathogen-associated molecular patterns, which are recognized by pattern recognition receptors, such as NOD1. N. gonorrhoeae is especially wasteful, losing 15% of its peptidoglycan fragments to the extracellular environment via inefficient recycling, compared to the 4-5% lost by other Neisseria species.

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HPLC of radiolabeled peptidoglycan shows more fragments released with gonococcal vs meningococcal ampG gene

The scientists confirmed the peptidoglycan shedding was due to poor recycling, and not an increase in fragment generation, by looking at the ampG genes of the different Neisseria species. By replacing the native ampG gene with the gonococcal version in asymptomatic colonizers N. sicca or N. mucosa, the scientists observed an increase in peptidoglycan shedding. Although a pathogen, N. meningiditis can also colonize without causing disease, which may be in part due to its minimal shedding. Replacing the meningococcal ampG with the gonococcal ampG led to almost 40% more peptidoglycan release from this strain (see right).

The difference appears to be in the sequence itself, since neither mRNA nor protein levels were higher in gonococcal ampG variants (if anything, the gonococcal transcript were lower). The sequences of the meningococcal and gonococcal AmpG proteins vary in only nine amino acids, and by generating chimeric constructs and then using site-directed mutagenesis, the team was able to pinpoint the three amino acids that affect recycling efficiency.

The large amounts of peptidoglycan shed by N. gonorrhoeae are more likely to alert the immune system to an unwelcome microbial stranger, leading to inflammation and immune cell influx. Given the similarity of N. meningitidis peptidoglycan release levels to other, nonpathogenic Neisseria species, the results of this study help explain why N. meningitidis can sometimes colonize without causing overt or immediate symptoms, while N. gonorrhoeae infection is almost always accompanied by a strong inflammatory response.

Photo credits: N. gonorrhoeae TEM, Figure from JBacteriology article

Julie Wolf

ASM Communications Social Media Specialist Julie Wolf spent her research career focused on medical mycology and infectious disease. Broadly interested in microbiology and scientific communication, she has taught at Long Island University and the community biolab Genspace and has written for the Scientista Foundation and Scholastic’s Science World magazine. Follow her on Twitter for more ASM and Microbiology highlights at @JulieMarieWolf.