Cytochrome c‐based domain modularity governs genus‐level diversification of electron transfer to dissimilatory nitrite reduction

Abstract

SummaryThe genus Neisseria contains two pathogenic species (N. meningitidis and N. gonorrhoeae) in addition to a number of commensal species that primarily colonize mucosal surfaces in man. Within the genus, there is considerable diversity and apparent redundancy in the components involved in respiration. Here, we identify a unique c-type cytochrome (cN) that is broadly distributed among commensal Neisseria, but absent in the pathogenic species. Specifically, cN supports nitrite reduction in N. gonorrhoeae strains lacking the cytochromes c5 and CcoP established to be critical to NirK nitrite reductase activity. The c-type cytochrome domain of cN shares high sequence identity with those localized c-terminally in c5 and CcoP and all three domains were shown to donate electrons directly to NirK. Thus, we identify three distinct but paralogous proteins that donate electrons to NirK. We also demonstrate functionality for a N. weaverii NirK variant with a C-terminal c-type heme extension. Taken together, modular domain distribution and gene rearrangement events related to these respiratory electron carriers within Neisseria are concordant with major transitions in the macroevolutionary history of the genus. This work emphasizes the importance of denitrification as a selectable trait that may influence speciation and adaptive diversification within this largely host-restricted bacterial genus.

Highly diverse nirK genes comprise two major clades that harbour ammonium-producing denitrifiers

“…Recent NirK analysis of the commensal bacterium Neisseria weaveri revealed high sequence similarity between the C-terminus c -type heme and other Neisserial NirK cytochrome electron carriers, i.e . Ccop and c 5 cytochromes [ 31 ], suggesting it might function as an alternative electron transport route to NirK providing an adaptive advantage in nitrite limiting environments. In contrast, these C-terminus extensions are not found in pathogenic Neisseria sp., further underlining their potential adaptive benefit linked to distinct lifestyles.…”

Characterization of a Unique Tetrasaccharide and Distinct Glycoproteome in the O -Linked Protein Glycosylation System of Neisseria elongata subsp. glycolytica

“…We chose here to focus our efforts on the type strain of N. elongata subsp. glycolytica (ATCC 29315) as it (i) is amenable to genetic manipulation (29), (ii) expresses a characterized type IV pilus (comprised of pilin, the most abundant glycoprotein in characterized species) (29), (iii) occupies a deeply branching position in neisserial phylogeny (27), and (iv) showed evidence of protein glycosylation in a previous study (30).…”

“…The same behavior was observed previously for the N. elongata subsp. glycolytica c N protein (a c-type monoheme cytochrome) (30). Thus, these four proteins display behavior consistent with being substrates for glycosylation.…”

Nanotechnological Strategies for Protein Delivery

“…Proteins performed essential functions, such as catalyzing biochemical reactions [ 1 ], signal transduction [ 2 ], defensive functions [ 3 ], regulatory functions [ 4 , 5 ], controlling cell fates [ 6 ], providing cellular and tissue structure [ 7 , 8 ], as molecule carriers [ 9 , 10 , 11 ], and maintaining a fine balance between cell survival and programmed death. For this reason, proteins are called the “engines of life”.…”