Mapping niche-specific two-component system requirements in uropathogenic Escherichia coli.

Sensory systems allow pathogens to differentiate between different niches and respond to stimuli within them. A major mechanism through which bacteria sense and respond to stimuli in their surroundings is two-component systems (TCSs). TCSs allow for the detection of multiple stimuli to lead to a highly controlled and rapid change in gene expression. Here, we provide a comprehensive list of TCSs important for the pathogenesis of uropathogenic Escherichia coli (UPEC). UPEC accounts for >75% of urinary tract infections (UTIs) worldwide. UTIs are most prevalent among people assigned female at birth, with the vagina becoming colonized by UPEC in addition to the gut and the bladder. In the bladder, adherence to the urothelium triggers E. coli invasion of bladder cells and an intracellular pathogenic cascade. Intracellular E. coli are safely hidden from host neutrophils, competition from the microbiota, and antibiotics that kill extracellular E. coli. To survive in these intimately connected, yet physiologically diverse niches E. coli must rapidly coordinate metabolic and virulence systems in response to the distinct stimuli encountered in each environment. We hypothesized that specific TCSs allow UPEC to sense these diverse environments encountered during infection with built-in redundant safeguards. Here, we created a library of isogenic TCS deletion mutants that we leveraged to map distinct TCS contributions to infection. We identify-for the first time-a comprehensive panel of UPEC TCSs that are critical for infection of the genitourinary tract and report that the TCSs mediating colonization of the bladder, kidneys, or vagina are distinct.IMPORTANCEWhile two-component system (TCS) signaling has been investigated at depth in model strains of Escherichia coli, there have been no studies to elucidate-at a systems level-which TCSs are important during infection by pathogenic Escherichia coli. Here, we report the generation of a markerless TCS deletion library in a uropathogenic E. coli (UPEC) isolate that can be leveraged for dissecting the role of TCS signaling in different aspects of pathogenesis. We use this library to demonstrate, for the first time in UPEC, that niche-specific colonization is guided by distinct TCS groups.

Mapping Niche-specific Two-Component System Requirements in Uropathogenic Escherichia coli.

Sensory systems allow pathogens to differentiate between different niches and respond to stimuli within them. A major mechanism through which bacteria sense and respond to stimuli in their surroundings is two-component systems (TCSs). TCSs allow for the detection of multiple stimuli to lead to a highly controlled and rapid change in gene expression. Here, we provide a comprehensive list of TCSs important for the pathogenesis of uropathogenic Escherichia coli (UPEC). UPEC accounts for >75% of urinary tract infections (UTIs) worldwide. UTIs are most prevalent among people assigned female at birth, with the vagina becoming colonized by UPEC in addition to the gut and the bladder. In the bladder, adherence to the urothelium triggers E. coli invasion of bladder cells and an intracellular pathogenic cascade. Intracellular E. coli are safely hidden from host neutrophils, competition from the microbiota, and antibiotics that kill extracellular E. coli. To survive in these intimately connected, yet physiologically diverse niches E. coli must rapidly coordinate metabolic and virulence systems in response to the distinct stimuli encountered in each environment. We hypothesized that specific TCSs allow UPEC to sense these diverse environments encountered during infection with built-in redundant safeguards. Here, we created a library of isogenic TCS deletion mutants that we leveraged to map distinct TCS contributions to infection. We identify - for the first time - a comprehensive panel of UPEC TCSs that are critical for infection of the genitourinary tract and report that the TCSs mediating colonization of the bladder, kidneys, or vagina are distinct.

COVID-19 threatens the progress of humanised childbirth: a qualitative study of giving birth during the pandemic in Brazil.

The stressful nature of the early months of the COVID-19 pandemic severely impacted the quality of maternity care. The purpose of this study was to understand and explore the labour and delivery experiences for women who were diagnosed with COVID-19 in Brazil during this time. Between July and October 2020, we conducted 28 semi-structured interviews with postpartum women who tested positive for COVID-19 prior to delivering at a tertiary hospital in Fortaleza, Brazil. Interview transcripts were coded, and we carried out a thematic analysis using three domains of the World Health Organization's model of intrapartum care for a positive childbirth experience as a framework. During labour and delivery, women experienced varying levels of respect, with many women reporting feeling mistreated by their healthcare team because of their COVID-19 diagnosis. Due to COVID-19 hospital protocols that denied companions or visitors, women reported feeling unsupported and isolated, especially during the mandatory quarantine. Women also experienced varying levels of effective communication, with some women citing they felt the staff were often fearful, and either avoidant or disrespectful. A minority of women reported that the staff appeared to be respectful and receptive to their needs. Our findings provide preliminary evidence that the strain of the COVID-19 pandemic on health professionals potentially results in ineffective communication and mistreatment during labour and delivery. Embedding respectful and humanised childbirth principles into emergency maternal healthcare protocols may improve the childbirth experience for women with COVID-19, as well as for women during future public health emergencies.

Ensuring Equitable Implementation of Telemedicine in Perinatal Care.

The use of telemedicine in U.S. perinatal care has drastically increased during the coronavirus disease 2019 (COVID-19) pandemic, and will likely continue given the national focus on high-value, patient-centered care. If implemented in an equitable manner, telemedicine has the potential to reduce disparities in care access and related outcomes that stem from systemic racism, implicit biases and other forms of discrimination within our health care system. In this commentary, we address implementation factors that should be considered to ensure that disparities are not widened as telemedicine becomes more integrated into care delivery.

Invasion of vaginal epithelial cells by uropathogenic Escherichia coli.

Host-associated reservoirs account for the majority of recurrent and oftentimes recalcitrant infections. Previous studies established that uropathogenic E. coli - the primary cause of urinary tract infections (UTIs) - can adhere to vaginal epithelial cells preceding UTI. Here, we demonstrate that diverse urinary E. coli isolates not only adhere to, but also invade vaginal cells. Intracellular colonization of the vaginal epithelium is detected in acute and chronic murine UTI models indicating the ability of E. coli to reside in the vagina following UTI. Conversely, in a vaginal colonization model, E. coli are detected inside vaginal cells and the urinary tract, indicating that vaginal colonization can seed the bladder. More critically, bacteria are identified inside vaginal cells from clinical samples from women with a history of recurrent UTI. These findings suggest that E. coli can establish a vaginal intracellular reservoir, where it may reside safely from extracellular stressors prior to causing an ascending infection.