Pleiotropy complicates a trade-off between phage resistance and antibiotic resistance.

Bacteria frequently encounter selection by both antibiotics and lytic bacteriophages. However, the evolutionary interactions between antibiotics and phages remain unclear, in particular, whether and when phages can drive evolutionary trade-offs with antibiotic resistance. Here, we describe Escherichia coli phage U136B, showing it relies on two host factors involved in different antibiotic resistance mechanisms: 1) the efflux pump protein TolC and 2) the structural barrier molecule lipopolysaccharide (LPS). Since TolC and LPS contribute to antibiotic resistance, phage U136B should select for their loss or modification, thereby driving a trade-off between phage resistance and either of the antibiotic resistance mechanisms. To test this hypothesis, we used fluctuation experiments and experimental evolution to obtain phage-resistant mutants. Using these mutants, we compared the accessibility of specific mutations (revealed in the fluctuation experiments) to their actual success during ecological competition and coevolution (revealed in the evolution experiments). Both tolC and LPS-related mutants arise readily during fluctuation assays, with tolC mutations becoming more common during the evolution experiments. In support of the trade-off hypothesis, phage resistance via tolC mutations occurs with a corresponding reduction in antibiotic resistance in many cases. However, contrary to the hypothesis, some phage resistance mutations pleiotropically confer increased antibiotic resistance. We discuss the molecular mechanisms underlying this surprising pleiotropic result, consideration for applied phage biology, and the importance of ecology in evolution of phage resistance. We envision that phages may be useful for the reversal of antibiotic resistance, but such applications will need to account for unexpected pleiotropy and evolutionary context.

Genitourinary syndrome of lactation: a new perspective on postpartum and lactation-related genitourinary symptoms.

BACKGROUND: The genitourinary syndrome of menopause (GSM) is a well-documented condition characterized by a range of genitourinary symptoms in peri- and postmenopausal women. As with GSM, postpartum lactating women experience reduced estrogen and androgen levels. However, there is limited research on the impact of symptoms during the postpartum breastfeeding period. OBJECTIVES: The aim was to review the literature for genitourinary health in the postpartum breastfeeding population and summarize key findings and potential treatments. METHODS: We performed a comprehensive literature review in PubMed, Google Scholar, and Scopus from inception of database to November 2023 using the following keywords individually and in combination: "physiology of postpartum" or "physiology of lactogenesis" or "vulvovaginal health" or "vaginal atrophy" or "vaginal dryness" or "dyspareunia" or "urinary incontinence" or "lactation" or "breastfeeding" or "vaginal estrogen." All identified articles published in English were considered. Relevant studies were extracted, evaluated, and analyzed. The work presented in this article represents a summative review of the identified literature. RESULTS: During lactation, high levels of prolactin inhibit estrogen and androgen secretion via negative feedback, which leads to an increased prevalence of vulvovaginal atrophy, vaginal dryness, dyspareunia, and urinary incontinence in lactating postpartum women. Despite these highly prevalent and potentially devastating symptoms, there is a lack of consistent screening at postpartum visits and no treatment guidelines available to health care providers. CONCLUSION: Postpartum breastfeeding women experience similar physiology and symptoms to the postmenopausal phase, as seen in GSM. We propose the introduction of a novel term to describe the genitourinary changes seen in postpartum breastfeeding individuals: genitourinary syndrome of lactation. The diagnostic use of genitourinary syndrome of lactation will equip health care providers with an all-encompassing term to bring awareness to the symptoms experienced by postpartum breastfeeding individuals and lead to improved screening and treatment for the high numbers of individuals experiencing these genitourinary changes.