Abstract

Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide, and about 30% of the pneumococcal clinical isolates show type I pili-like structures. These long proteinaceous polymers extending from the bacterial surface are encoded by pilus islet 1 and play major roles in adhesion and host colonization. Pili expression is bistable and is controlled by the transcriptional activator RlrA. In this work, we demonstrate that the previously identified small noncoding RNA srn135 also participates in pilus regulation. Our findings show that srn135 is generated upon processing of the 5′-UTR region of rrgA messenger and its deletion prevents the synthesis of RrgA, the main pili adhesin. Moreover, overexpression of srn135 increases the expression of all pili genes and rises the percentage of piliated bacteria within a clonal population. This regulation is mediated by the stabilization of rlrA mRNA since higher levels of srn135 increase its half-life to 165%. Our findings suggest that srn135 has a dual role in pilus expression acting both in cis- (on the RrgA levels) and in trans- (modulating the levels of RlrA) and contributes to the delicate balance between pili expressing and non-expressing bacteria.

Highlights

  • Accepted: 1 September 2021Streptococcus pneumoniae is a prominent cause of pneumonia, meningitis, septicemia, and acute otitis media worldwide [1] and is the leading cause of vaccine-preventable deaths in children under five years old

  • The small, noncoding srn135 was previously identified as an intergenic sRNA flanked by rlrA and rrgA Open Reading Frames (ORFs) [44]

  • We studied the role of srn135 as a novel regulator of Pilus Islet 1 (PI-1) expression

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Summary

Introduction

Accepted: 1 September 2021Streptococcus pneumoniae is a prominent cause of pneumonia, meningitis, septicemia, and acute otitis media worldwide [1] and is the leading cause of vaccine-preventable deaths in children under five years old (www.who.int; accessed on 2 August 2019). S. pneumoniae possesses a range of factors that facilitate nasopharyngeal colonization by enhancing host–cell attachment and have been implicated in the pathogenesis of invasive pneumococcal diseases [2,3]. These include pilus-like structures, long multimeric filaments that decorate bacterial surfaces [4,5,6,7,8]. Pili structures have been identified in a number of Gram-positive organisms. They differ from the Gram-negative pili in their genes, biochemistry, and structure as reviewed in [9,10]. Two types of pili have been identified in S. pneumoniae: type 1 encoded by

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