Biology subjects

Hoang, T.-M.

Publications and source records attributed to Hoang, T.-M..

2 recordsLinked to original sources

bioRxiv2024

The Pseudomonas aeruginosa PrrF sRNAs promote biofilm formation at body temperature

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes both acute and chronic infections in vulnerable populations. Treatment of P. aeruginosa infections is increasingly challenging due to multi-drug resistance as well as biofilm formation that further increases antibiotic tolerance. Iron, which is sequestered by the host innate immune system, is also a key nutrient that required for P. aeruginosa biofilm formation. Previous work showed that the iron-responsive PrrF small regulatory RNAs (sRNAs), which are key to P. aeruginosas iron starvation response and required for virulence in murine lung infection, are dispensable for biofilm formation. However, these studies were performed using flow-cell biofilms at room temperature. Here we demonstrate a temperature dependency for PrrF in P. aeruginosa biofilm formation - the genes for these sRNAs are required for optimal biofilm formation at 37{degrees}C but not 25{degrees}C. We further show that the {Delta}prrF mutant lacks a yet-to-be identified surface appendage that is produced at 37{degrees}C but not 25{degrees}C. These studies demonstrate that the importance of the PrrF sRNAs in P. aeruginosa biofilm formation at body temperature and reveal a previously under-appreciated role of temperature in iron homeostasis and P. aeruginosa biofilm physiology. IMPORTANCEBiofilm formation is a critical aspect of pathogenesis for many microbial pathogens as it confers increased tolerance to the host immune system and antimicrobial treatments. Pseudomonas aeruginosa is an opportunistic pathogen that forms biofilms during infection, resulting in antimicrobial tolerance and treatment failure. Iron is a known requirement for P. aeruginosa biofilm formation, yet the precise role of iron homeostasis in biofilm physiology remains unclear. Here we show that temperature alters the requirement for the PrrF small regulatory RNAs, key components of P. aeruginosas iron starvation response, for biofilm formation. Specifically, PrrF is required for the optimal formation of biofilms in flow cells at 37{degrees}C but not 25{degrees}C, yet most flow-cell biofilm studies are conducted at 25{degrees}C. These results demonstrate a previously under-appreciated role of temperature in P. aeruginosa biofilm physiology.

microbiology↗

bioRxiv2023

The heme-responsive PrrH sRNA regulates Pseudomonas aeruginosa pyochelin gene expression

Pseudomonas aeruginosa is an opportunistic pathogen that requires iron for growth and virulence, yet this nutrient is sequestered by the innate immune system during infection. When iron is limiting, P. aeruginosa expresses the PrrF1 and PrrF2 small regulatory RNAs (sRNAs), which post-transcriptionally repress expression of non-essential iron-containing proteins thus sparing this nutrient for more critical processes. The genes for the PrrF1 and PrrF2 sRNAs are arranged in tandem on the chromosome, allowing for the transcription of a longer heme-responsive sRNA, termed PrrH. While the functions of PrrF1 and PrrF2 have been studied extensively, the role of PrrH in P. aeruginosa physiology and virulence is not well understood. In this study, we performed transcriptomic and proteomic studies to identify the PrrH regulon. In shaking cultures, the pyochelin synthesis proteins were increased in two distinct prrH mutants compared to wild type, while the mRNAs for these proteins were not affected by prrH mutation. We identified complementarity between the PrrH sRNA and sequence upstream of the pchE mRNA, suggesting potential for PrrH to directly regulate expression of genes for pyochelin synthesis. We further showed that pchE mRNA levels were increased in the prrH mutants when grown in static but not shaking conditions. Moreover, we discovered controlling for the presence of light was critical for examining the impact of PrrH on pchE expression. As such, our study reports on the first likely target of the PrrH sRNA and highlights key environmental variables that will allow for future characterization of PrrH function. ImportanceIn the human host, iron is predominantly in the form of heme, which Pseudomonas aeruginosa can acquire as an iron source during infection. We previously showed that the iron-responsive PrrF sRNAs are critical for mediating iron homeostasis during P. aeruginosa infection; however the function of the heme-responsive PrrH sRNA remains unclear. In this study, we identified genes for pyochelin siderophore biosynthesis, which mediate uptake of inorganic iron, as a novel target of PrrH regulation. This study therefore highlights a novel relationship between heme availability and siderophore biosynthesis in P. aeruginosa.

microbiology↗