# Investigation of the essential, conserved RodZ protein in peptidoglycan synthesis in the ovococcal pathogen, Streptococcus pneumoniae

> **NIH NIH F31** · TRUSTEES OF INDIANA UNIVERSITY · 2020 · $492

## Abstract

On February 27th, to prioritize the development of new and effective antibiotic treatments, the World Health
Organization (WHO) released its first Global Priority Pathogens List (global PPL) in 2017; of the 12 pathogens
highlighted Streptococcus pneumoniae (Spn) ranked 10th. The global PPL recognizes pathogens that pose a
significant threat to global health based on mortality, healthcare and community burden, prevalence of
resistance, transmissibility, and treatability. Spn poses a significant threat to global health as this
bacterium is no longer susceptible to the major antibiotic penicillin. The main target of antibiotics is the
bacterial cell wall, a complex mesh that protects bacteria from an arsenal of both environmental and medical
threats. As a Gram-positive ovococcus, Spn, employs two mechanisms to synthesize its protective cell wall:
peripheral and septal peptidoglycan (PG) synthesis. These mechanisms require complex, multi-protein
machines whose spatiotemporal regulation is largely unknown. Interestingly, Spn lacks the actin homolog and
master PG-synthesis-localization orchestrator MreB of rod-shaped bacteria. Curiously, MreB's interaction
partner, RodZ, is encoded in the Spn genome and is essential. Note, in rod-shaped bacteria, MreB
localization and the subsequent proper localization of the PG synthesis machinery is dependent on RodZ.
Since RodZ remains essential in Spn, we speculate RodZ possesses additional functions tangential to binding
MreB. Furthermore, in all bacteria, several ambiguities exist regarding the function and localization pattern of
RodZ and the position of RodZ in the assembly hierarchy of the PG machinery. The proposed work directly
addresses these ambiguities in Spn and thereby will develop new knowledge towards the prevention of
disease. Moreover, the proposed work aligns with the NIH's mission to increase global health as cell wall
synthesis proteins are promising targets for novel antibiotics. Lastly, greater resolution of the mechanisms by
which bacteria construct the cell wall is imperative to global health as antibiotic resistance is on the rise.
Hypothesis: We hypothesize that RodZ is a key member of the peripheral PG synthesis machinery and may
interact with the actin homolog FtsA to coordinate the localization of the PG synthesis machinery in Spn.
The following research aims will elucidate the essential role of RodZ in cell wall synthesis of Spn:
Aim 1) Determine key residues essential for RodZ's function in Spn via a reverse genetics approach
Aim 2) Characterize RodZ's interacting partners and temporal localization pattern in vivo. For which co-
immunoprecipitation experiments and co-localization assays will be used.
Aim 3) Investigate RodZ's putative role as a cellular regulator. Towards which end, RNA sequencing and
subsequent chromatin or RNA immunoprecipitation sequencing methods will be employed.

## Key facts

- **NIH application ID:** 10154488
- **Project number:** 3F31AI138430-02S1
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** Melissa Mae Lamanna
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $492
- **Award type:** 3
- **Project period:** 2018-08-01 → 2020-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10154488

## Citation

> US National Institutes of Health, RePORTER application 10154488, Investigation of the essential, conserved RodZ protein in peptidoglycan synthesis in the ovococcal pathogen, Streptococcus pneumoniae (3F31AI138430-02S1). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10154488. Licensed CC0.

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