Mycobacterium tuberculosis genetic features associated with pulmonary tuberculosis severity.

OBJECTIVES: Mycobacterium tuberculosis (Mtb) infections result in a wide spectrum of clinical presentations but without proven Mtb genetic determinants. Herein, we hypothesized that the genetic features of Mtb clinical isolates, such as specific polymorphisms or microdiversity, may be linked to tuberculosis (TB) severity. METHODS: A total of 234 patients with pulmonary TB (including 193 drug-susceptible and 14 monoresistant cases diagnosed between 2017 and 2020 and 27 multidrug-resistant cases diagnosed between 2010 and 2020) were stratified according to TB disease severity, and Mtb genetic features were explored using whole genome sequencing, including heterologous single-nucleotide polymorphism (SNP), calling to explore microdiversity. Finally, we performed a structural equation modeling analysis to relate TB severity to Mtb genetic features. RESULTS: The clinical isolates from patients with mild TB carried mutations in genes associated with host-pathogen interaction, whereas those from patients with moderate/severe TB carried mutations associated with regulatory mechanisms. Genome-wide association study identified an SNP in the promoter of the gene coding for the virulence regulator espR, statistically associated with moderate/severe disease. Structural equation modeling and model comparisons indicated that TB severity was associated with the detection of Mtb microdiversity within clinical isolates and to the espR SNP. CONCLUSION: Taken together, these results provide a new insight to better understand TB pathophysiology and could provide a new prognosis tool for pulmonary TB severity.

Vaginal Tampon Colonization by Staphylococcus aureus in Healthy Women.

Tampons recovered from a cohort of 737 healthy women (median age, 32 years) were analyzed for the presence of Staphylococcus aureus A total of 198 tampons (27%) were colonized by S. aureus, 28 (4%) by a strain producing toxic shock syndrome toxin 1 (TSST-1). S. aureus was detected more frequently in tampons that did not require an applicator for their insertion (74/233 [32%] versus 90/381 [24%]; odds ratio [OR] = 1.51 [95% confidence interval, 1.04 to 2.17]) and in women who used an intrauterine device for contraception (53/155 [34%] versus 145/572 [27%]; OR = 1.53 [95% confidence interval, 1.05 to 2.24]). The S. aureus strains isolated from tampons belonged to 22 different clonal complexes (CCs). The most prevalent CC was CC398 agr1 (n = 57 [27%]), a clone that does not produce superantigenic toxins, followed by CC30 agr3 (n = 27, 13%), producing TSST-1 (24/27 [89%]), the principal clone of S. aureus involved in menstrual toxic shock syndrome (MTSS).IMPORTANCE Menstrual toxic shock syndrome (MTSS) is an uncommon severe acute disease that occurs in healthy menstruating women colonized by TSST-1-producing S. aureus who use intravaginal protection, such as tampons and menstrual cups. The catamenial product collected by the protection serves as a growth medium for S. aureus and allows TSST-1 production. Previous studies evaluated the prevalence of genital colonization by S. aureus by vaginal swabbing, but they did not examine tampon colonization. This study demonstrated a high prevalence of tampon colonization by S. aureus and the presence of the CC30 TSST-1 S. aureus clone responsible for MTSS in tampons from healthy women. The results support the vaginal carriage of this lineage in healthy women. In addition, the higher prevalence of S. aureus within tampons that do not require an applicator indicates a crucial role for handwashing before tampon handling to decrease the risk of tampon contamination.