Commensal Neisseria cinerea impairs Neisseria meningitidis microcolony development and reduces pathogen colonisation of epithelial cells

Abstract

It is increasingly being recognised that the interplay between commensal and pathogenic bacteria can dictate the outcome of infection. Consequently, there is a need to understand how commensals interact with their human host and influence pathogen behaviour at epithelial surfaces. Neisseria meningitidis, a leading cause of sepsis and meningitis, exclusively colonises the human nasopharynx and shares this niche with several other Neisseria species, including the commensal Neisseria cinerea. Here, we demonstrate that during adhesion to human epithelial cells N. cinerea co-localises with molecules that are also recruited by the meningococcus, and show that, similar to N. meningitidis, N. cinerea forms dynamic microcolonies on the cell surface in a Type four pilus (Tfp) dependent manner. Finally, we demonstrate that N. cinerea colocalises with N. meningitidis on the epithelial cell surface, limits the size and motility of meningococcal microcolonies, and impairs the effective colonisation of epithelial cells by the pathogen. Our data establish that commensal Neisseria can mimic and affect the behaviour of a pathogen on epithelial cell surfaces.

The Human Microbiome as a Focus of Antibiotic Discovery: Neisseria mucosa Displays Activity Against Neisseria gonorrhoeae

“…Little is known about production of secondary metabolites by Neisseria , however, some nonpathogenic species have been shown to inhibit pathogens. N. lactamica ( Deasy et al, 2015 ) and N. cinerea ( Custodio et al, 2020 ) inhibit the colonization of N. meningitidis in human infection and epithelial cell culture models, respectively, and DNA released by N. elongata and multiple other nonpathogenic Neisseria species kills N. gonorrhoeae ( Kim et al, 2019 ). In the project described here, we initiated a search for neisserial antimicrobial secondary metabolites by analyzing a panel of 36 nonpathogenic Neisseria strains for activity against other Neisseria , including N. gonorrhoeae.…”

Type VI secretion system killing by commensal Neisseria is influenced by the spatial dynamics of bacteria

“…Thus, one way for susceptible bacteria to evade T6SS killing is to avoid direct contact with attacking cells (Borenstein et al, 2015; Smith et al, 2020). In Neisseria , the Tfp is a key mediator of interbacterial and interspecies interactions (Custodio et al, 2020; Higashi et al, 2011b) and pilus-mediated interactions influence the spatial structure of a growing community (Oldewurtel et al, 2015; Zöllner et al, 2017). In N. gonorrhoeae, non-piliated bacteria segregate to the expanding front of the colony and Tfp-mediated spatial reorganisation can allow bacteria to avoid external stresses or strains competing for resources (Oldewurtel et al, 2015; Zöllner et al, 2017).…”

“…The human nasopharynx hosts a polymicrobial community (Kumpitsch et al, 2019; Marchesi et al, 2017; Ramos-Sevillano et al, 2019), which can include the obligate human pathobiont Neisseria meningitidis , as well as related but generally non-pathogenic, commensal Neisseria species (Diallo et al, 2016; Dorey et al, 2019; Gold et al, 1978; Knapp and Hook, 1988; Sheikhi et al, 2015). In vivo studies have demonstrated an inverse relationship between carriage of commensal Neisseria lactamica and N. meningitidis (Deasy et al, 2015), while in vitro studies have revealed that some commensal Neisseria demonstrate potentially antagonistic effects against their pathogenic relatives (Custodio et al, 2020; Kim et al, 2019). Commensal and pathogenic Neisseria species have also been shown to interact closely in mixed populations (Custodio et al, 2020; Higashi et al, 2011a).…”

“…In vivo studies have demonstrated an inverse relationship between carriage of commensal Neisseria lactamica and N. meningitidis (Deasy et al, 2015), while in vitro studies have revealed that some commensal Neisseria demonstrate potentially antagonistic effects against their pathogenic relatives (Custodio et al, 2020; Kim et al, 2019). Commensal and pathogenic Neisseria species have also been shown to interact closely in mixed populations (Custodio et al, 2020; Higashi et al, 2011a). Social interactions among Neisseria are mediated by surface structures known as Type IV pili (Tfp).…”

“…We recently demonstrated that the pathogen N. meningitidis closely interacts with commensal Neisseria cinerea on human epithelial cell surfaces in a Tfp-dependent manner (Custodio et al, 2020). Here, whole genome sequence analysis revealed that the N. cinerea isolate used in our studies encodes a T6SS.…”