# Mucin inhibits pneumococcal stationary phase autolysis

> **NIH NIH F32** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2024 · $73,828

## Abstract

PROJECT SUMMARY
Streptococcus pneumoniae (pneumococci) are Gram-positive cocci that usually exists as a commensal of the
human nasopharyngeal mucosa but are often characterized as pathogens due to its ability to disseminate from
the nasopharynx and into the inner ear and lower respiratory tract. High bacterial load during lower respiratory
tract infection, such as bronchitis and pneumonia, restricts the efficacy of the mucociliary escalator, leading to
inflammation and limited gas exchange. Mucus serves as a protective barrier between the lung epithelium and
the environment and a nutritional source for the pneumococcus. We found that mucin serves as a key nutritional
cue for S. pneumoniae, preventing autolysis and facilitating prolonged bacterial survival in stationary phase
compared to traditional media. Since mucin is abundant in pneumococcal environmental niches, we wanted to
assess the impact of mucin on various aspects pneumococcal biology. We found that mucin effectively blocked
pneumococcal autolysis via inhibition of the primary autolysin, LytA. A fundamental aspect of pneumococcal
biology is the capacity of the bacterium to rapidly undergo autolysis following entry into stationary phase during
standard in vitro cultivation leading to a rapid loss in culture viability. We observed that mucin-mediated autolysis
inhibition not only prevented this process but also promoted long-term stationary phase survival of the
pneumococcus both planktonically and in biofilms. This phenotype was highly conserved amongst genetically
diverse strain backgrounds and independent of capsular serotype. The mucin-mediated autolysis inhibition was
found to be dependent upon the direct inhibitory activity of physiological concentrations mucin on LytA using
peptidoglycan hydrolysis assays. Additionally, mice that over produce mucus were found to have enhanced
pneumococcal nasal colonization. Based on these preliminary findings, we aim to determine 1) the specificity
underlying mucin-mediated autolysis inhibition; 2) the impact of mucin-mediated autolysis inhibition on
pneumococcal evolutionary tools such cytotoxicity; and 3) the genetic determinants that are required for
prolonged stationary phase survival in mucin. Environmental context is critical to understanding the fundamental
biology of pathogens. The primary host niche for the pneumococcus is the nasopharynx, which is replete with
mucins. These data suggest that environmental niches harboring mucins may promote pneumococcal
colonization over invasive infection by preventing host cell death and prolonged bacterial survival.

## Key facts

- **NIH application ID:** 10997930
- **Project number:** 1F32AI186447-01
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Cydney N Johnson
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $73,828
- **Award type:** 1
- **Project period:** 2024-08-01 → 2025-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10997930

## Citation

> US National Institutes of Health, RePORTER application 10997930, Mucin inhibits pneumococcal stationary phase autolysis (1F32AI186447-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10997930. Licensed CC0.

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