Immune exclusion by naturally acquired secretory IgA against pneumococcal pilus-1

Binsker, Ulrike; Lees, John A.; Hammond, Alexandria J.; Weiser, Jeffrey N.

doi:10.1172/jci132005

Cited by 33 publications

(58 citation statements)

References 82 publications

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“…In order to detect robust mucus binding to hNF, we utilized a previously described Type 23F isolate with an inserted type-1 pilus (Type 23F::pilus-1) and confirmed its robust adherence to hNF in our assay ( Fig. 2C) (5). Binding of the Type 23F pilus-1 to large mucus particles in hNF was confirmed using alcian blue staining ( Fig.…”

Section: Screening Pneumococcal Surface Factors For Their Effect On Mmentioning

confidence: 63%

“…The lack of an effect for RlrA was expected, as mNLs lack naturally-acquired anti-pilus S-IgA ( Fig. 2B) (5). Next, we tested pneumococcal surface enzymes for their role in mucus binding (Table 1).…”

Section: Screening Pneumococcal Surface Factors For Their Effect On Mmentioning

confidence: 91%

“…We focused on pneumococcal surface factors that had been shown, or hypothesized, to interact with mucus (2,5,6,24,25,8). Of the four surface factors (genes)…”

Section: Screening Pneumococcal Surface Factors For Their Effect On Mmentioning

confidence: 99%

“…This effect of capsule in blocking mucus interactions could be due to repulsion by capsular polysaccharides, which are anionic for all but a few serotypes, with negatively-charged mucus. To examine whether other pneumococcal surface factors affect bacterial-mucus interactions, our lab developed a solid phase adherence assay to look directly at the interactions between Spn and nasal secretions obtained from humans (hNF, human nasal fluid) (5). Results from this assay demonstrated that Spn adherence to hNF was dominant among pneumococcal isolates expressing type-1 pilus.…”

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confidence: 99%

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Neuraminidase B controls neuraminidase A-dependent mucus production and evasion

Hammond

Binsker

Aggarwal

et al. 2020

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Binding of Streptococcus pneumoniae (Spn) to nasal mucus leads to entrapment and clearance via mucociliary activity during colonization. To identify Spn factors allowing for evasion of mucus binding, we used a solid-phase adherence assay with immobilized mucus of human and murine origin. Spn bound large mucus particles through interactions with carbohydrate moieties. Mutants lacking neuraminidase (nanA) or neuraminidase B (nanB) showed increased mucus binding that correlated with diminished removal of terminal sialic acid residues on bound mucus. The non-additive activity of the two enzymes raised the question why Spn expresses two neuraminidases and suggested they function in the same pathway. Transcriptional analysis demonstrated expression of nanA depends on the enzymatic function of NanB. As transcription of nanA is increased in the presence of sialic acid, our findings suggest that sialic acid liberated from host glycoconjugates by the secreted enzyme NanB induces the expression of the cell-associated enzyme NanA. The absence of detectable mucus desialylation in the nanA mutant, in which NanB is still expressed, suggests that NanA is responsible for the bulk of the modification of host glycoconjugates. Thus, our studies describe a functional role for NanB in sialic acid sensing in the host. The contribution of the neuraminidases in vivo was then assessed in a murine model of colonization. Although mucus-binding mutants showed an early advantage, this was only observed in a competitive infection, suggesting a complex role of neuraminidases. Histologic examination of the upper respiratory tract demonstrated that Spn stimulates mucus production in a neuraminidase-dependent manner. Thus, an increase production of mucus containing secretions appears to be balanced, in vivo, by decreased mucus binding. We postulate that through the combined activity of its neuraminidases, Spn evades mucus binding and mucociliary clearance, which is needed to counter neuraminidase-mediated stimulation of mucus secretions.Author SummaryStreptococcus pneumoniae (Spn) is a leading mucosal pathogen, whose host interaction begins with colonization of the upper respiratory tract. While there has been extensive investigation into bacterial interaction with epithelial cells, there is little understanding of bacterial-mucus interactions. Our study used mucus of human and murine origin and a murine model of colonization to study mucus associations involving Spn. The main findings reveal i) the enzymatic activity of Spn’s neuraminidases (NanA and NanB) contribute to mucus evasion through removing terminal sialic acid, ii) the enzymatic activity of NanB controls expression of the main neuraminidase, NanA, and iii) Spn induces sialic acid containing mucus secretions in vivo in a neuraminidase-dependent manner. We postulate that during colonization, neuraminidase-dependent reduction in mucus binding enables evasion of mucociliary clearance, which is necessary to counter neuraminidase-mediated stimulation of mucus secretions. Thus, our study provides new insights into the role of Spn neuraminidases on colonization.

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Section: Screening Pneumococcal Surface Factors For Their Effect On Mmentioning

confidence: 63%

Section: Screening Pneumococcal Surface Factors For Their Effect On Mmentioning

confidence: 91%

“…We focused on pneumococcal surface factors that had been shown, or hypothesized, to interact with mucus (2,5,6,24,25,8). Of the four surface factors (genes)…”

Section: Screening Pneumococcal Surface Factors For Their Effect On Mmentioning

confidence: 99%

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confidence: 99%

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Neuraminidase B controls neuraminidase A-dependent mucus production and evasion

Hammond

Binsker

Aggarwal

et al. 2020

Preprint

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“…The low carriage rate of pneumococci among adults has been attributed by other studies to development of natural immunity [18]. The upper respiratory tract apparently appears a disadvantageous niche for streptococcus pneumoniae due to development of mucosal host defenses such as sIgA [19,20]. Also vaccination with PCV has resulted into the development of herd immunity in the adult population against S. pneumoniae [12].…”

Section: Discussionmentioning

confidence: 99%

Pneumococcal Carriage and Antibiotic Susceptibility Patterns in Mother-Baby Pairs in a rural community in Eastern Uganda

Gm¹,

Naloli²,

Sebwami³

et al. 2019

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Objective: This study aimed to estimate pneumococcal carriage and determine antibiotic susceptibility patterns of the pneumococci isolated in the mother-baby pairs in Ngora district after the roll out of the pneumococcal vaccine. We hypothesized that high carriage of S. pneumoniae in mothers leads to carriage in their babies and hence a greater chance of contacting pneumoniae. Results: Consecutive sampling technique was used to select 152 mother-baby pairs from the community visits and those seeking care at the health facility. We collected nasal swabs from both baby and mother for culture and sensitivity using the Kirby-Bauer’s agar disc diffusion method. This study found that there was a low prevalence of pneumococcal carriage in the mother-baby pair in Ngora district. We also observed high rates microbial resistance to Penicillin which is the first-line management of pneumonia in Uganda. The relationship between pneumococcal carriage and immunization status suggest that Pneumococcal vaccine is protective against pneumococcal carriage. Resistance of S. pneumoniae to the commonly used antibiotics was high. Key words: Pneumococcal carriage, mother-baby pair, antibiotic susceptibility pattern, immunization with PCV 10, Eastern Uganda.

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