Chlamydia trachomatis suppresses host cell store-operated Ca2+ entry and inhibits NFAT/calcineurin signaling.

The obligate intracellular bacterium, Chlamydia trachomatis, replicates within a parasitophorous vacuole termed an inclusion. During development, host proteins critical for regulating intracellular calcium (Ca2+) homeostasis interact with the inclusion membrane. The inclusion membrane protein, MrcA, interacts with the inositol-trisphosphate receptor (IP3R), an ER cationic channel that conducts Ca2+. Stromal interaction molecule 1 (STIM1), an ER transmembrane protein important for regulating store-operated Ca2+ entry (SOCE), localizes to the inclusion membrane via an uncharacterized interaction. We therefore examined Ca2+ mobilization in C. trachomatis infected cells. Utilizing a variety of Ca2+ indicators to assess changes in cytosolic Ca2+ concentration, we demonstrate that C. trachomatis impairs host cell SOCE. Ca2+ regulates many cellular signaling pathways. We find that the SOCE-dependent NFAT/calcineurin signaling pathway is impaired in C. trachomatis infected HeLa cells and likely has major implications on host cell physiology as it relates to C. trachomatis pathogenesis.

Human Immunodeficiency Virus/Sexually Transmitted Infection Testing Preferences for Young Black Men Who Have Sex With Men in the Southeastern United States: Implications for a Post-COVID-19 Era.

BACKGROUND: Little is known regarding human immunodeficiency virus (HIV)/sexually transmitted infection (STI) testing preferences for location, staffing, and hours of operation among Young Black men who have sex with men (YBMSM) in the Southeastern United States, a population at high risk for HIV/STIs. We used a discrete choice experiment to explore these preferences. METHODS: Young Black men who have sex with men ages 16 to 35 years in Birmingham, AL and Jackson, MS completed online surveys evaluating their preferences (best/worst) for HIV/STI testing locations, staffing, hours, method of results notification, and cost. They also selected preferred combinations of these variables through choice tasks. Results were analyzed using joint best/worst and discrete choice experiment models. RESULTS: Between June 2018 and December 2019, participants in Alabama (n = 54) and Mississippi (n = 159) completed online surveys. Both groups preferred stationary testing locations over mobile testing vans, with the most significant difference favoring STI testing-only clinics in Mississippi and local health departments in Alabama (P < 0.001). Technician-performed tests or self-testing were significantly less preferred compared with clinician-performed testing for both groups (P < 0.0001 and P < 0.0001, respectively). Free testing and phone results notification (versus text) were preferred by both groups. The most desirable combination among all participants was weekday clinician-performed testing at the health department for $5. CONCLUSIONS: Young Black men who have sex with men in the Southeastern United States prefer traditional testing locations staffed by experienced personnel. Combination choices are influenced by services that are low or no cost. More research is needed to inform the best way(s) to provide affordable, high-quality HIV/STI testing services for YBMSM, particularly in the post-COVID-19 era when sexual health care delivery models are evolving toward home-based and remote health-focused strategies.

Case Report: Emergent Resistance in a Treatment-Naive Person With Human Immunodeficiency Virus Under Bictegravir-Based Therapy.

Few instances of treatment-emergent resistance to bictegravir have been reported in the literature. We describe a case of treatment-emergent resistance to bictegravir in a person recently diagnosed with human immunodeficiency virus who developed M184V and R263K mutations while on therapy.

Epidemiology, Clinical Features, and Outcomes of Hospitalized Adults with COVID-19: Early Experience from an Academic Medical Center in Mississippi.

OBJECTIVES: To describe the demographics, clinical characteristics, and outcomes of hospitalized adults with coronavirus disease 2019 (COVID-19) in an academic medical center in the southern United States. METHODS: Retrospective, observational cohort study of all adult patients (18 years and older) consecutively admitted with laboratory-confirmed severe acute respiratory syndrome-coronavirus-2 infection between March 13 and April 25, 2020 at the University of Mississippi Medical Center. All of the patients either survived to hospital discharge or died during hospitalization. Demographics, body mass index, comorbidities, clinical manifestations, and laboratory findings were collected. Patient outcomes (need for invasive mechanical ventilation and in-hospital death) were analyzed. RESULTS: One hundred patients were included, 53% of whom were women. Median age was 59 years (interquartile range 44-70) and 66% were younger than 65. Seventy-five percent identified themselves as Black, despite representing 58% of hospitalized patients at our institution in 2019. Common comorbid conditions included hypertension (68%), obesity (65%), and diabetes mellitus (31%). Frequent clinical manifestations included shortness of breath (76%), cough (75%), and fever (64%). Symptoms were present for a median of 7 days (interquartile range 4-7) on presentation. Twenty-four percent of patients required mechanical ventilation and, overall, 19% died (67% of those requiring mechanical ventilation). Eighty-four percent of those who died were Black. On multivariate analysis, ever smoking (odds ratio [OR] 5.9, 95% confidence interval [CI] 1.2-28.6) and history of diabetes mellitus (OR 5.9, 95% CI 1.5-24.3) were associated with mortality, and those admitted from home were less likely to die (vs outside facility, OR 0.2, 95% CI 0.0-0.7). Neither age, sex, race, body mass index, insurance status, nor rural residence was independently associated with mortality. CONCLUSIONS: Our study adds evidence that Black patients appear to be overrepresented in those hospitalized with and those who die from COVID-19, likely a manifestation of adverse social determinants of health. These findings should help guide preventive interventions targeting groups at higher risk of acquiring and developing severe COVID-19 disease.

Infection and nuclear interaction in mammalian cells by 'Candidatus Berkiella cookevillensis', a novel bacterium isolated from amoebae.

BACKGROUND: 'Candidatus Berkiella cookevillensis' and 'Ca. Berkiella aquae' have previously been described as intranuclear bacteria of amoebae. Both bacteria were isolated from amoebae and were described as appearing within the nuclei of Acanthamoeba polyphaga and ultimately lysing their host cells within 4 days. Both bacteria are Gammaproteobacteria in the order Legionellales with the greatest similarity to Coxiella burnetii. Neither bacterium grows axenically in artificial culture media. In this study, we further characterized 'Ca. B. cookevillensis' by demonstrating association with nuclei of human phagocytic and nonphagocytic cell lines. RESULTS: Transmission electron microscopy (TEM) and confocal microscopy were used to confirm nuclear co-localization of 'Ca. B. cookevillensis' in the amoeba host A. polyphaga with 100% of cells having bacteria co-localized with host nuclei by 48 h. TEM and confocal microscopy demonstrated that the bacterium was also observed to be closely associated with nuclei of human U937 and THP-1 differentiated macrophage cell lines and nonphagocytic HeLa human epithelial-like cells. Immunofluorescent staining revealed that the bacteria-containing vacuole invaginates the nuclear membranes and appears to cross from the cytoplasm into the nucleus as an intact vacuole. CONCLUSION: Results of this study indicate that a novel coccoid bacterium isolated from amoebae can infect human cell lines by associating with the host cell nuclei, either by crossing the nuclear membranes or by deeply invaginating the nuclear membranes. When associated with the nuclei, the bacteria appear to be bound within a vacuole and replicate to high numbers by 48 h. We believe this is the first report of such a process involving bacteria and human cell lines.

Extragenital Chlamydia and Gonorrhea in Young Black Men Who Have Sex With Men: Missed Treatment Opportunities for Human Immunodeficiency Virus-Infected Men Who Have Sex With Men?

OBJECTIVES: This study of young black men who have sex with men (YBMSM) assessed the prevalence of extragenital chlamydia and gonorrhea among those testing negative for urethral infections, and compared prevalence of both by human immunodeficiency virus (HIV) status. METHODS: A convenience sample of 609 YBMSM was recruited for a cross-sectional study from 2 sexual health clinics located in Jackson, MS. To detect Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), nucleic acid amplification testing was performed on urine, rectal swabs, and oral swabs. OraSure was used to detect HIV. RESULTS: Seventy-three percent of all chlamydia infections and 77% of gonorrhea infections were found from anal and oral swabs in the absence of urethral positivity. Compared with HIV-uninfected men, HIV-infected men were significantly more likely to have pharyngeal chlamydia (P = 0.03), multiple CT infections (P = 0.02), rectal NG (P < 0.001), multiple NG infections (P = 0.04), both CT/NG rectal infections (P = 0.001). CONCLUSIONS: As much as three quarters of all chlamydia and gonorrhea infections may be missed when only urine-based nucleic acid amplification testing is used to screen YBMSM for bacterial sexually transmitted infections. These missed opportunities for diagnosis may be particularly likely among HIV-infected YBMSM.

Is Patient-Reported Exposure a Reliable Indicator for Anogenital Gonorrhea and Chlamydia Screening in Young Black Men Who Have Sex With Men?

Among 485 young black men who have sex with men recruited in Jackson, MS, 90-day anal sexual exposure significantly predicted rectal infection, but 19.4% of rectal infections would have been missed among men denying receptive anal sex. Reports of consistent condom use were associated with lower infection rates only in men reporting insertive anal sex.

Is Sex with Older Male Partners Associated with Higher Sexual Risk Behavior Among Young Black MSM?

Participants at a sexual health clinic completed a survey with questions regarding sexual risk behavior and partner characteristics. Of 585 participants eligible for analysis, 124 reported generally having older male partners. These participants were significantly more likely to be HIV-infected (p < 0.001), have four or more sex partners as a "bottom" (p = 0.04), have concurrent partners (p = 0.01), and have partners suspected of having an sexually transmitted infection (p = 0.05) than participants without older partners. With analysis restricted to HIV- individuals, risk behaviors did not differ significantly between the groups. HIV- individuals with older partners may be at increased risk of HIV infection due to increased HIV prevalence among older sexual partners and not due to increased risk behaviors with these partners.

Does Age Matter Among Young Black Men Who Have Sex With Men? A Comparison of Risk Behaviors Stratified by Age Category.

The purpose of this study is to assess whether different sexual risk behavior exists among young Black men who have sex with men (YBMSM) as a function of age. A total of 382 YBMSM completed a computer-assisted self-interview at a sexual health clinic. The frequency/prevalence of fifteen sexual risk behaviors was compared between three groups (ages 16-19, 20-25, and 26-29, respectively) in the 90 days prior to enrollment in the study. Regression models were used to control for the confounding influence of Human Immunodeficiency Virus (HIV) status. One hundred seven participants were HIV-infected at study enrollment. Of the 15 measures assessed, none significantly differed among the groups. These null findings did not change in multivariate analyses. Our findings suggest that there is no differential sexual risk based on age among YBMSM and that this group should be considered a homogenous population with regards to intervention strategies that aim to reduce the sexual risk behaviors of YBMSM.

Sexual Network Profiles and Risk Factors for STIs Among African-American Sexual Minorities in Mississippi: A Cross-Sectional Analysis.

This cross-sectional study assessed sexually transmitted infection (STI) prevalence, socio-demographic characteristics, substance use, sexual behaviors, and sexual network profiles among African American sexual minorities in Jackson, Mississippi. Bivariate chi-square tests and generalized estimating equation (GEE) models explored individual and partner-related factors. Compared to their heterosexual counterparts, male African American sexual minorities reported fewer sex partners (odds ratios [OR] 0.33, 95% confidence intervals [CI] 0.16-0.65) and lower concurrency levels (OR 0.42, 95%CI 0.24-0.72). African American sexual minority women reported greater substance abuse, more sex partners (OR 2.54, 95%CI 1.47-4.38), higher concurrency levels (OR 1.81, 95%CI 1.24-2.64), and more transactional sex (OR 2.52, 95%CI 1.25-5.11). These results highlight the need for nuanced STI interventions tailored to African American sexual minorities in Mississippi.

Prevalence and predictors of concurrent sexual partnerships in a predominantly African American population in Jackson, Mississippi.

Concurrent sexual partnerships, or sexual partnerships that overlap in time, have been associated with HIV and sexually transmitted infections (STI). How best to measure concurrency and the personal characteristics and predictors of concurrency are not yet well understood. We compared two frequently used concurrency definitions, including a self-reported measure based on participant response regarding overlapping sex with partners, and the UNAIDS measure based on overlapping dates of last sex and intention to have sex again. We performed multivariable logistic regression analyses to identify socio-demographic, behavioral, and structural predictors of concurrency among 1,542 patients at an urban STI clinic in Jackson, Mississippi. Nearly half (44 %) reported concurrency based on self-reported sex with other partners, and 26 % reported concurrency according to the UNAIDS concurrency measure. Using the self-reported concurrency measure, the strongest predictors of concurrency were perceived partner concurrency, drug use at last sex, having more than 10 lifetime partners, and being recently incarcerated. Strongest predictors of concurrency using the UNAIDS measure were lifetime number of partners and perceived partner concurrency. Concurrency is highly prevalent in this population in the Deep South and social, structural and behavioral factors were important predictors of concurrency for both measures. Future research should use time anchored data collection methods and biomarkers to assess whether both definitions of concurrency are associated with HIV outcomes.