Adjuvants can be used to potentiate the function of antibiotics whose efficacy has been reduced by acquired or intrinsic resistance. In the present study, we discovered that human milk oligosaccharides (HMOs) sensitize strains of group B Streptococcus (GBS) to trimethoprim (TMP), an antibiotic to which GBS is intrinsically resistant. Reductions in the MIC of TMP reached as high as 512-fold across a diverse panel of isolates. To better understand HMOs’ mechanism of action, we characterized the metabolic response of GBS to HMO treatment using ultrahigh-performance liquid chromatography–high-resolution tandem mass spectrometry (UPLC-HRMS/MS) analysis. These data showed that when challenged by HMOs, GBS undergoes significant perturbations in metabolic pathways related to the biosynthesis and incorporation of macromolecules involved in membrane construction. This study represents reports the metabolic characterization of a cell that is perturbed by HMOs. IMPORTANCE Group B Streptococcus is an important human pathogen that causes serious infections during pregnancy which can lead to chorioamnionitis, funisitis, premature rupture of gestational membranes, preterm birth, neonatal sepsis, and death. GBS is evolving antimicrobial resistance mechanisms, and the work presented in this paper provides evidence that prebiotics such as human milk oligosaccharides can act as adjuvants to restore the utility of antibiotics.

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Arkansas passed Act 626, to be known as the "Arkansas Save Adolescents From Experimentation (SAFE) Act," 1 thus becoming the first state to outlaw gender-affirming care (GAC) for transgender youth. Many other states are considering similar bills, some of which include provisions that impose criminal penalties on health care professionals.Although Act 626 is among the more severe examples of antitransgender legislation, the United States has a history of similar legislation. Since 2015, coordinated attacks against lesbian, gay, bisexual, transgender, and queer (LGBTQ) rights have escalated in an unprecedented fashion. The targets of these attacks have shifted from marriage equality, bathroom access, and sports participation to the most recent attacks on transgender youths and their bodies. Act 626 is a part of recent nationwide efforts to limit access to GAC for transgender youths. This year represents a critical time for transgender young people, with new bills targeting their access to health care in at least 21 states.Approximately 1.4 million adults (0.6% of adults in the United States) and 150 000 youths (0.7% of youths aged 13-17 years in the US) identify as transgender. 2 A large body of research dedicated to transgender health indicates that GAC, including prescribing or using puberty blockers such as gonadotropin-releasing hormone agonists, (GnRHa), hormone therapy (eg, testosterone or estrogen therapy), and gender-affirming surgery, is medically necessary for patients experiencing gender dysphoria. 3 The discordant effects of societal gender roles and gendered activities on transgender youths are exacerbated during puberty, when masculinizing and feminizing anatomical changes take place. Transgender youths may find that pubertal changes worsen the dissonance between their anatomy and their gender identity, contributing to gender dysphoria and increasing the risk for negative health outcomes. Consider the case of a transgender woman who was assigned male at birth. 4 At the age of 7 years, this individual started showing an interest in playing with dolls and dressing in her sister's clothes, activities that her parents discouraged. Fearing disapproval from those around her, she began to withdraw socially. At the onset of puberty, she developed a hatred for her male physical features, leading to 2 suicide attempts by 16 years of age. As her gender dysphoria progressed, she experienced suicidal behavior, self-mutilation, depression, and poor mental health. Gender-affirming care is medically necessary and, in this case, lifesaving for transgender youth with gender dysphoria. 3 In addition, sexual and gender minority adolescents are more likely to delay care and avoid health screenings, for fear of discrimination. Legislation that

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