Elucidation of independently modulated genes in Streptococcus pyogenes reveals carbon sources that control its expression of hemolytic toxins.

Autor:	Hirose Y; Department of Microbiology, Graduate School of Dentistry, Osaka University , Suita, Osaka, Japan.; Department of Pediatrics, University of California at San Diego School of Medicine , La Jolla, California, USA., Poudel S; Department of Bioengineering, University of California San Diego , La Jolla, California, USA., Sastry AV; Department of Bioengineering, University of California San Diego , La Jolla, California, USA., Rychel K; Department of Bioengineering, University of California San Diego , La Jolla, California, USA., Lamoureux CR; Department of Bioengineering, University of California San Diego , La Jolla, California, USA., Szubin R; Department of Bioengineering, University of California San Diego , La Jolla, California, USA., Zielinski DC; Department of Bioengineering, University of California San Diego , La Jolla, California, USA., Lim HG; Department of Bioengineering, University of California San Diego , La Jolla, California, USA.; Department of Biological Engineering, Inha University, Michuhol-gu , Incheon, South Korea., Menon ND; Department of Pediatrics, University of California at San Diego School of Medicine , La Jolla, California, USA.; School of Biotechnology, Amrita Vishwa Vidyapeetham , Amritapuri, Kerala, India., Bergsten H; Department of Pediatrics, University of California at San Diego School of Medicine , La Jolla, California, USA., Uchiyama S; Department of Pediatrics, University of California at San Diego School of Medicine , La Jolla, California, USA., Hanada T; Department of Microbiology, Graduate School of Dentistry, Osaka University , Suita, Osaka, Japan., Kawabata S; Department of Microbiology, Graduate School of Dentistry, Osaka University , Suita, Osaka, Japan.; Center for Infectious Diseases Education and Research, Osaka University , Suita, Osaka, Japan., Palsson BO; Department of Bioengineering, University of California San Diego , La Jolla, California, USA., Nizet V; Department of Pediatrics, University of California at San Diego School of Medicine , La Jolla, California, USA.; Skaggs School of Pharmaceutical Sciences, University of California at San Diego , La Jolla, California, USA.
Jazyk:	angličtina
Zdroj:	MSystems [mSystems] 2023 Jun 29; Vol. 8 (3), pp. e0024723. Date of Electronic Publication: 2023 Jun 06.
DOI:	10.1128/msystems.00247-23
Abstrakt:	Streptococcus pyogenes can cause a wide variety of acute infections throughout the body of its human host. An underlying transcriptional regulatory network (TRN) is responsible for altering the physiological state of the bacterium to adapt to each unique host environment. Consequently, an in-depth understanding of the comprehensive dynamics of the S. pyogenes TRN could inform new therapeutic strategies. Here, we compiled 116 existing high-quality RNA sequencing data sets of invasive S. pyogenes serotype M1 and estimated the TRN structure in a top-down fashion by performing independent component analysis (ICA). The algorithm computed 42 independently modulated sets of genes (iModulons). Four iModulons contained the nga-ifs-slo virulence-related operon, which allowed us to identify carbon sources that control its expression. In particular, dextrin utilization upregulated the nga-ifs-slo operon by activation of two-component regulatory system CovRS-related iModulons, altering bacterial hemolytic activity compared to glucose or maltose utilization. Finally, we show that the iModulon-based TRN structure can be used to simplify the interpretation of noisy bacterial transcriptome data at the infection site. IMPORTANCE S. pyogenes is a pre-eminent human bacterial pathogen that causes a wide variety of acute infections throughout the body of its host. Understanding the comprehensive dynamics of its TRN could inform new therapeutic strategies. Since at least 43 S . pyogenes transcriptional regulators are known, it is often difficult to interpret transcriptomic data from regulon annotations. This study shows the novel ICA-based framework to elucidate the underlying regulatory structure of S. pyogenes allows us to interpret the transcriptome profile using data-driven regulons (iModulons). Additionally, the observations of the iModulon architecture lead us to identify the multiple regulatory inputs governing the expression of a virulence-related operon. The iModulons identified in this study serve as a powerful guidepost to further our understanding of S. pyogenes TRN structure and dynamics. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu