The utilization of educational resources published by the Thoracic Surgery Residents Association.

Objective: The Thoracic Surgery Residents Association (TSRA) is a trainee-led cardiothoracic surgery organization in North America that has published a multitude of educational resources. However, the utilization of these resources remains unknown. Methods: Surveys were constructed, pilot-tested, and emailed to 527 current cardiothoracic trainees (12 questions) and 780 former trainees who graduated between 2012 and 2019 (16 questions). The surveys assessed the utilization of TSRA educational resources in preparing for clinical practice as well as in-training and American Board of Thoracic Surgery (ABTS) certification examinations. Results: A total of 143 (27%) current trainees and 180 (23%) recent graduates responded. A higher proportion of recent graduates compared with current trainees identified as male (84% vs 66%; P = .001) and graduated from 2- or 3-year traditional training programs (81% vs 41%; P < .001), compared with integrated 6-year (8% vs 49%; P < .001) or 4 + 3 (11% vs 10%; P = .82) pathways. Current trainees most commonly used TSRA resources to prepare for the in-training exam (75%) and operations (73%). Recent graduates most commonly used them to prepare for Oral and/or Written Board Exams (92%) and the in-training exam (89%). Among recent graduates who passed the ABTS Oral Board Exam on the first attempt, 82% (97/118) used TSRA resources to prepare, versus only 48% (25/52) of recent graduates who passed after multiple attempts, failed, have not taken the exam, or preferred not to answer (P < .001). Conclusions: Current cardiothoracic trainees and recent graduates have utilized TSRA educational resources extensively, including to prepare for in-training and ABTS Board examinations.

Transcriptional Silencing by TsrA in the Evolution of Pathogenic Vibrio cholerae Biotypes.

Vibrio cholerae is a globally important pathogen responsible for the severe epidemic diarrheal disease called cholera. The current and ongoing seventh pandemic of cholera is caused by El Tor strains, which have completely replaced the sixth-pandemic classical strains of V. cholerae To successfully establish infection and disseminate to new victims, V. cholerae relies on key virulence factors encoded on horizontally acquired genetic elements. The expression of these factors relies on the regulatory architecture that coordinates the timely expression of virulence determinants during host infection. Here, we apply transcriptomics and structural modeling to understand how type VI secretion system regulator A (TsrA) affects gene expression in both the classical and El Tor biotypes of V. cholerae We find that TsrA acts as a negative regulator of V. cholerae virulence genes encoded on horizontally acquired genetic elements. The TsrA regulon comprises genes encoding cholera toxin (CT), the toxin-coregulated pilus (TCP), and the type VI secretion system (T6SS), as well as genes involved in biofilm formation. The majority of the TsrA regulon is carried on horizontally acquired AT-rich genetic islands whose loss or acquisition could be directly ascribed to the differences between the classical and El Tor strains studied. Our modeling predicts that the TsrA protein is a structural homolog of the histone-like nucleoid structuring protein (H-NS) oligomerization domain and is likely capable of forming higher-order superhelical structures, potentially with DNA. These findings describe how TsrA can integrate into the intricate V. cholerae virulence gene expression program, controlling gene expression through transcriptional silencing.IMPORTANCE Pathogenic Vibrio cholerae strains express multiple virulence factors that are encoded by bacteriophage and chromosomal islands. These include cholera toxin and the intestinal colonization pilus called the toxin-coregulated pilus, which are essential for causing severe disease in humans. However, it is presently unclear how the expression of these horizontally acquired accessory virulence genes can be efficiently integrated with preexisting transcriptional programs that are presumably fine-tuned for optimal expression in V. cholerae before its conversion to a human pathogen. Here, we report the role of a transcriptional regulator (TsrA) in silencing horizontally acquired genes encoding important virulence factors. We propose that this factor could be critical to the efficient acquisition of accessory virulence genes by silencing their expression until other signals trigger their transcriptional activation within the host.

TsrA Regulates Virulence and Intestinal Colonization in Vibrio cholerae.

Pathogenic strains of Vibrio cholerae require careful regulation of horizontally acquired virulence factors that are largely located on horizontally acquired genomic islands (HAIs). While TsrA, a Vibrionaceae-specific protein, is known to regulate the critical HAI virulence genes toxT and ctxA, its broader function throughout the genome is unknown. Here, we find that deletion of tsrA results in genomewide expression patterns that heavily correlate with those seen upon deletion of hns, a widely conserved bacterial protein that regulates V. cholerae virulence. This correlation is particularly strong for loci on HAIs, where all differentially expressed loci in the ΔtsrA mutant are also differentially expressed in the Δhns mutant. Correlation between TsrA and H-NS function extends to in vivo virulence phenotypes where deletion of tsrA compensates for the loss of ToxR activity in V. cholerae and promotes wild-type levels of mouse intestinal colonization. All in all, we find that TsrA broadly controls V. cholerae infectivity via repression of key HAI virulence genes and many other targets in the H-NS regulon.IMPORTANCE Cholera is a potentially lethal disease that is endemic in much of the developing world. Vibrio cholerae, the bacterium underlying the disease, infects humans utilizing proteins encoded on horizontally acquired genetic material. Here, we provide evidence that TsrA, a Vibrionaceae-specific protein, plays a critical role in regulating these genetic elements and is essential for V. cholerae virulence in a mouse intestinal model.