Loss of Meningococcal PilU Delays Microcolony Formation and Attenuates Virulence
            <i>In Vivo</i>

Eriksson, Jens; Eriksson, Olaspers Sara; Jonsson, Ann‐Beth

doi:10.1128/iai.06354-11

Cited by 22 publications

(25 citation statements)

References 34 publications

(42 reference statements)

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“…In this study, we investigated the importance of epithelial cells and cell-derived factors for microcolony dispersal. We demonstrated that the previously observed short and synchronized dispersal of microcolonies [41] requires the presence of live epithelial cells but not direct contact between cells and bacteria. Microcolony dispersal could be induced by a low-molecular weight host cell-derived factor that accumulated in cell-conditioned medium (i.e., CM) in absence of infectious agent.…”

Section: Discussionmentioning

confidence: 67%

Host cell-derived lactate functions as an effector molecule in Neisseria meningitidis microcolony dispersal

et al. 2017

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The development of meningococcal disease, caused by the human pathogen Neisseria meningitidis, is preceded by the colonization of the epithelial layer in the nasopharynx. After initial adhesion to host cells meningococci form aggregates, through pilus-pilus interactions, termed microcolonies from which the bacteria later detach. Dispersal from microcolonies enables access to new colonization sites and facilitates the crossing of the cell barrier; however, this process is poorly understood. In this study, we used live-cell imaging to investigate the process of N. meningitidis microcolony dispersal. We show that direct contact with host cells is not required for microcolony dispersal, instead accumulation of a host-derived effector molecule induces microcolony dispersal. By using a host-cell free approach, we demonstrated that lactate, secreted from host cells, initiate rapid dispersal of microcolonies. Interestingly, metabolic utilization of lactate by the bacteria was not required for induction of dispersal, suggesting that lactate plays a role as a signaling molecule. Furthermore, Neisseria gonorrhoeae microcolony dispersal could also be induced by lactate. These findings reveal a role of host-secreted lactate in microcolony dispersal and virulence of pathogenic Neisseria.

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Section: Discussionmentioning

confidence: 67%

Host cell-derived lactate functions as an effector molecule in Neisseria meningitidis microcolony dispersal

et al. 2017

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“…While this shows that PNPase is required for full virulence in this mouse model, the mechanism for decreased bacterial survival is unclear. Previous studies of bacteremia that used the hyperaggregative nafA-and pilT-deficient N. meningitidis mutants showed that these mutants also displayed decreased survival (39,64). We cannot exclude the possibility that the decreased bacterial counts in blood were due to an increase in bacterial binding to host cells as a result of excessive aggregation.…”

Section: Discussionmentioning

confidence: 68%

Neisseria meningitidis Polynucleotide Phosphorylase Affects Aggregation, Adhesion, and Virulence

et al. 2016

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Neisseria meningitidis autoaggregation is an important step during attachment to human cells. Aggregation is mediated by type IV pili and can be modulated by accessory pilus proteins, such as PilX, and posttranslational modifications of the major pilus subunit PilE. The mechanisms underlying the regulation of aggregation remain poorly characterized. Polynucleotide phosphorylase (PNPase) is a 3=-5= exonuclease that is involved in RNA turnover and the regulation of small RNAs. In this study, we biochemically confirm that NMC0710 is the N. meningitidis PNPase, and we characterize its role in N. meningitidis pathogenesis. We show that deletion of the gene encoding PNPase leads to hyperaggregation and increased adhesion to epithelial cells. The aggregation induced was found to be dependent on pili and to be mediated by excessive pilus bundling. PNPase expression was induced following bacterial attachment to human cells. Deletion of PNPase led to global transcriptional changes and the differential regulation of 469 genes. We also demonstrate that PNPase is required for full virulence in an in vivo model of N. meningitidis infection. The present study shows that PNPase negatively affects aggregation, adhesion, and virulence in N. meningitidis.

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“…PilU was long speculated to play a role in Tfp retraction due its co‐transcription with and structural similarity to PilT. Ngo and Neisseria meningitidis mutants deleted of pilU show differences in microcolony formation and infection dynamics compared to wt, further implicating a role for PilU in Tfp retraction (Park et al ., ; Eriksson et al ., ). Our findings lend support to this idea.…”

Section: Discussionmentioning

confidence: 87%

Perturbing the acetylation status of the Type IV pilus retraction motor, PilT, reduces Neisseria gonorrhoeae viability

Hockenberry

Post

Rhodes

et al. 2018

Molecular Microbiology

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Post-translational acetylation is a common protein modification in bacteria. It was recently reported that Neisseria gonorrhoeae acetylates the Type IV pilus retraction motor, PilT. Here, we show recombinant PilT can be acetylated in vitro and acetylation does not affect PilT ultrastructure. To investigate the function of PilT acetylation, we mutated an acetylated lysine, K117, to mimic its acetylated or unacetylated forms. These mutations were not tolerated by wild-type N. gonorrhoeae, but they were tolerated by N. gonorrhoeae carrying an inducible pilE when grown without inducer. We identified additional mutations in pilT and pilU that suppress the lethality of K117 mutations. To investigate the link between PilE and PilT acetylation, we found the lack of PilE decreases PilT acetylation levels and increases the amount of PilT associated with the inner membrane. Finally, we found no difference between wild-type and mutant cells in transformation efficiency, suggesting neither mutation inhibits Type IV pilus retraction. Mutant cells, however, form microcolonies morphologically distinct from wt cells. We conclude that interfering with the acetylation status of PilT greatly reduces N. gonorrhoeae viability, and mutations in pilT, pilU and pilE can overcome this lethality. We discuss the implications of these findings in the context of Type IV pilus retraction regulation.

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Loss of Meningococcal PilU Delays Microcolony Formation and Attenuates Virulence In Vivo

Cited by 22 publications

References 34 publications

Host cell-derived lactate functions as an effector molecule in Neisseria meningitidis microcolony dispersal

Host cell-derived lactate functions as an effector molecule in Neisseria meningitidis microcolony dispersal

Neisseria meningitidis Polynucleotide Phosphorylase Affects Aggregation, Adhesion, and Virulence

Perturbing the acetylation status of the Type IV pilus retraction motor, PilT, reduces Neisseria gonorrhoeae viability

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