# Novel Bacterial Small RNAs as Determinants of Rickettsial Virulence and Transmission

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2020 · $540,869

## Abstract

Project Summary/Abstract
Pathogenic Rickettsia species include Gram-negative bacteria known to cause human infections, namely
spotted fever (R. rickettsii and R. conorii) and typhus (R. prowazekii and R. typhi), with serious morbidity and
mortality. Tropism for microvascular endothelium, rapid escape from the phagosome, and growth/replication in
the nutrient-rich cytosol as obligate intracellular parasites leading to vascular inflammation and
dysfunction/damage constitute the salient features of rickettsial pathogenesis. Rickettsioses are vector-borne
infections transmitted in nature by infected arthropods, including ticks and fleas. Rickettsiae are capable of
circulating in their natural vectors through transstadial (horizontal) and transovarial (vertical) transmission and
undergo dramatic niche-specific transcriptomic adaptations during their life-cycle to adjust to diverse
environments in arthropod vectors and mammalian hosts. In this context, a major vacuity in our existing
knowledge is the lack of understanding of regulatory mechanisms supporting their adaptive and/or pathogenic
abilities in different host niches. Although small non-coding RNAs (sRNAs) are now firmly established as
universal features of pathogenic bacteria and major regulators of their transcriptomes, the discovery and
functional characterization of rickettsial sRNAs remained ignored until recently. We have now established and
published that sRNAs in Rickettsia species are not only plentiful and functional (based on the identification of
RC0877 and cydA as the respective target genes for novel R. conorii sRNAs Rc_sR35 and Rc_sR42, but are
also differentially expressed in human versus tick host cells and in target organs in a mouse model of
endothelial-target rickettsiosis akin to human disease. These findings serve as the foundation for a novel
paradigm and genesis of our hypothesis that pathogenic rickettsiae exploit a network of sRNAs to adapt to
host-specific environments (vectors vis-á-vis mammals) via modulation of gene expression. Having established
the presence of sRNAs in both major groups of pathogenic rickettsiae, we now propose to conduct a
comprehensive `compare and contrast' analysis of sRNA repertoire of R. conorii and R. typhi and their target
genes during infection of human and mouse microvascular endothelium and to perform mechanistic and
functional characterization of critically important rickettsial sRNAs [Aim 1]. We will next investigate their roles in
rickettsial maintenance in natural vectors and vector-to-host transmission
[Aim 2]
and as potential determinants
of virulence in the target organs of established murine models of R. conorii and R. typhi infection closely
recapitulating the pathophysiology of human rickettsioses
[Aim 3]
. At conclusion, the proposed scientific
enquiry will have a sustained positive impact through cataloging of novel rickettsial sRNAs and determination
of mechanistic and functional insights into transcriptome regulation durin...

## Key facts

- **NIH application ID:** 9934989
- **Project number:** 5R01AI127899-03
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Hema Prasad Narra
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $540,869
- **Award type:** 5
- **Project period:** 2018-06-13 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934989

## Citation

> US National Institutes of Health, RePORTER application 9934989, Novel Bacterial Small RNAs as Determinants of Rickettsial Virulence and Transmission (5R01AI127899-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9934989. Licensed CC0.

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