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Specific anaerobic taxa within the penile microbiome—the Bacteria Associated with Seroconversion, Inflammation and Immune Cells (BASIC) species—enhance HIV-1 susceptibility, in part by recruiting susceptible cells to the inner foreskin. However, their effect on epithelial barrier integrity has not been described. Using foreskin tissues and penile swabs from 116 males undergoing voluntary medical male circumcision, we assessed the relationship between BASIC species and foreskin epithelial thickness, junction protein expression, and cellular proliferation. The absolute abundance of BASIC species was associated with reduced tissue expression of the epithelial junction proteins claudin-1 and E-cadherin, and with elevated soluble E-cadherin in penile secretions, suggesting proteolytic cleavage. These effects were not seen in participants with a high abundance of control taxa without high levels of BASIC species. The BASIC species Prevotella bivia , but not Peptostreptococcus anaerobius or Dialister micraerophilus , was shown to directly degrade recombinant human E-cadherin and to increase the release of soluble E-cadherin from foreskin epithelial cells in vitro . In vivo BASIC species absolute abundance was also linked to a thicker nucleated epithelium and increased keratinocyte proliferation, with no change in stratum corneum thickness. Therefore, BASIC species may enhance penile HIV susceptibility by directly disrupting epithelial integrity, in addition to previously described target cell recruitment.

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide and are primarily caused by Escherichia coli . While E. coli is known to colonize both humans and food-producing animals, the extent to which zoonotic strains impact human disease remains poorly understood. Emerging evidence suggests that food animals may serve as an underrecognized reservoir for extraintestinal pathogenic E. coli (ExPEC). In this study, we used a genomic attribution model to quantify the contribution of zoonotic strains to UTIs in Southern California. We found that approximately 18% of E. coli UTIs were likely attributable to food animals. Individuals living in high-poverty neighborhoods had a 1.6-fold increased risk of zoonotic UTIs compared to those in low-poverty areas. These findings highlight zoonotic transmission as an important driver of UTIs and suggest that reducing ExPEC in food-animal reservoirs could help lower disease burden and address health disparities.

Globally, most Human Immunodeficiency Virus type 1 (HIV) transmission occurs through vaginal–penile sex (heterosexual transmission). The local immune environment at the site of HIV exposure is an important determinant of whether exposure during sex will lead to productive infection, and the vaginal and penile immune milieus are each critically shaped by the local microbiome. However, there are key differences in the microbial drivers of inflammation and immune quiescence at these tissue sites. In both, a high abundance of anaerobic taxa (e.g., Prevotella) is associated with an increased local density of HIV target cells and an increased risk of acquiring HIV through sex. However, the taxa that have been associated to date with increased risk in the vagina and penis are not identical. Just as importantly, the microbiota associated with comparatively less inflammation and HIV risk—i.e., the optimal microbiota—are very different at the two sites. In the vagina, Lactobacillus spp. are immunoregulatory and may protect against HIV acquisition, whereas on the penis, “skin type” flora such as Corynebacterium are associated with reduced inflammation. Compared to its vaginal counterpart, much less is known about the dynamics of the penile microbiome, the ability of clinical interventions to alter the penile microbiome, or the impact of natural/induced microbiome alterations on penile immunology and HIV risk.

Endemic human coronaviruses (HCoV) are capable of causing a range of diseases from the common cold to pneumonia. We evaluated the epidemiology and seasonality of endemic HCoVs in children hospitalized with clinical pneumonia and among community controls living in countries with a high HIV burden, namely South Africa and Zambia, between August 2011 to October 2013. Nasopharyngeal/oropharyngeal swabs were collected from all cases and controls and tested for endemic HCoV species and 12 other respiratory viruses using a multiplex real-time PCR assay. We found that the likelihood of detecting endemic HCoV species was higher among asymptomatic controls than cases (11% vs. 7.2%; 95% CI: 1.2–2.0). This was however only observed among children > 6 months and was mainly driven by the Betacoronavirus endemic species (HCoV-OC43 and –HKU1). Endemic HCoV species were detected through the year; however, in Zambia, the endemic Betacoronavirus species tended to peak during the winter months (May–August). There was no association between HIV status and endemic HCoV detection.

Background Coronal sulcus (CS) anaerobe abundance and IL-8 levels are linked to HIV acquisition, and are dramatically reduced after penile circumcision (PC). The distal urethra may be the site of some HIV acquisition before PC, and presumably most acquisition post PC. We describe the immune milieu and microbiome of the distal urethra in uncircumcised Ugandan men, and define the impact of PC. Participants consisted of HIV-negative, genital symptom-free adult Ugandan men undergoing PC ( n = 51). Urethral and coronal sulcus swabs were collected at baseline and at 6- and 12-months post-PC. Soluble immune factors were quantified by multiplex ELISA, and bacterial abundance assessed by 16S rRNA qPCR and sequencing. Results At baseline, the urethra was enriched compared to the CS for most cytokines (including IL-8 and MIP-1β) and soluble E-cadherin (sE-cadherin, an epithelial disruption marker), although CS levels of IL-1α and IL-1β were higher. Baseline total bacterial abundance was ≥ 20-fold higher in the CS than the urethra (median 27,100 vs. 1200 gene copies/swab, p = 0.001), and anaerobes comprised 58% of CS bacteria vs. 42% of urethral bacteria. PC did not alter urethral IL-8 (median 806 at baseline vs. 1130 pg/ml at 12 months; p = 0.062) and urethral sE-cadherin increased (113,223 vs. 158,385 pg/ml, p = 0.009), despite five- and sevenfold drops in total bacterial and anaerobe abundance after PC, respectively. However, PC dramatically reduced CS levels of sE-cadherin (15,843 vs. 837 pg/ml, p < 0.001) and most cytokines (IL-8; 34 vs. 3 pg/ml, p < 0.001), while reducing total bacterial and anaerobe abundance by 13-fold and 60-fold, respectively (both P ≤ 0.004). Conclusions The urethra is immunologically rich with characteristics of an HIV-susceptible tissue site. However, PC had no impact on urethral immunology and may have reduced epithelial integrity, despite modest reductions in total bacteria and anaerobes, suggesting that HIV protection from PC is not mediated via immune or microbiome alterations in the urethra. 6PgEasmsZ9wG1E4iwYa-kC Video abstract

Background Infections caused by antibiotic-resistant bacteria are increasingly frequent, burdening healthcare systems worldwide. As pathogens acquire resistance to all known antibiotics – i.e., become pan-resistant – treatment of the associated infections will become exceedingly difficult. We hypothesized that the emergence of pan-resistant bacterial pathogens will result in a sharp increase in human mortality. Methods We tested this hypothesis by modeling the impact of a single hypothetical pan-resistant Escherichia coli strain on sepsis deaths in the United States. We used long-term data on sepsis incidence, mortality rates, strain dynamics, and treatment outcomes to parameterize a set of models encompassing a range of plausible future scenarios. All models accounted for historical and projected temporal changes in population size and age distribution. Results The models suggest that sepsis deaths could increase 18- to 46-fold within 5 years of the emergence of a single pan-resistant E. coli strain. This large and rapid change contrasts sharply with the current expectation of gradual change under continuing multidrug-resistance. Conclusions Failure to prevent the emergence of pan-resistance would have dire consequences for public health. Plain Language Summary Antibiotic-resistant bacteria are an increasing risk to public health. As bacteria become resistant to all known antibiotics – i.e., become pan-resistant – treatment of infections will become extremely difficult. We hypothesized that the appearance of pan-resistant bacteria will result in a sharp increase in mortality. We tested this hypothesis using computer and mathematical modeling to see how a single hypothetical pan-resistant type of bacteria would impact deaths in the United States. Drawing from existing long-term data, deaths from infection in the general population could increase dramatically within 5 years of the emergence of a single pan-resistant type of common bacteria. Failing to prevent the emergence of pan-resistance would have dire consequences for public health. Koch et al. model scenarios of emergence of a single pan-resistant Escherichia coli strain in the United States. Findings suggest dire mortality outcomes and highlight the importance of measures to prevent the emergence of antimicrobial resistance.

Successfully educating urgent care patients on appropriate use and risks of antibiotics can be challenging. We assessed the conscious and subconscious impact various educational materials (informational handout, priming poster, and commitment poster) had on urgent care patients' knowledge and expectations regarding antibiotics. Stratified Block Randomized Control Trial. Urgent care centers (UCCs) in Colorado, Florida, Georgia, and New Jersey. Urgent care patients. We randomized 29 UCCs across six study arms to display specific educational materials (informational handout, priming poster, and commitment poster). The primary intention-to-treat (ITT) analysis evaluated whether the materials impacted patient knowledge or expectations of antibiotic prescribing by assigned study arm. The secondary as-treated analysis evaluated the same outcome comparing patients who recalled seeing the assigned educational material and patients who either did not recall seeing an assigned material or were in the control arm. Twenty-seven centers returned 2,919 questionnaires across six study arms. Only 27.2% of participants in the intervention arms recalled seeing any educational materials. In our primary ITT analysis, no difference in knowledge or expectations of antibiotic prescribing was noted between groups. However, in the as-treated analysis, the handout and commitment poster were associated with higher antibiotic knowledge scores. Educational materials in UCCs are associated with increased antibiotic-related knowledge among patients when they are seen and recalled; however, most patients do not recall passively displayed materials. More emphasis should be placed on creating and drawing attention to memorable patient educational materials.

The foreskin is a site of heterosexual acquisition of HIV-1 among uncircumcised men. However, some men remain HIV-negative despite repeated, unprotected vaginal intercourse with HIV-positive partners, while others become infected after few exposures. The foreskin microbiome includes a diverse group of anaerobic bacteria that have been linked to HIV acquisition. However, these anaerobes tend to coassociate, making it difficult to determine which species might increase HIV risk and which may be innocent bystanders. Here, we show that 6 specific anaerobic bacterial species, Peptostreptococcus anaerobius, Prevotella bivia, Prevotella disiens, Dialister propionicifaciens, Dialister micraerophilus, and a genetic near neighbor of Dialister succinatiphilus, significantly increased cytokine production, recruited HIV-susceptible CD4+ T cells to the inner foreskin, and were associated with HIV acquisition. This strongly suggests that the penile microbiome increases host susceptibility to HIV and that these species are potential targets for microbiome-based prevention strategies.

We studied how patient beliefs regarding the need for antibiotics, as measured by expectation scores, and antibiotic prescribing outcome affect patient satisfaction using data from 2,710 urgent-care visits. Satisfaction was affected by antibiotic prescribing among patients with medium–high expectation scores but not among patients with low expectation scores.

Antimicrobial use in food-animal production selects for antimicrobial-resistant that can be transmitted to humans via contaminated meat products. California Senate Bill 27 (SB27), which took effect on January 1, 2018, restricts the use of medically important antimicrobials in California food-animal production. Over time, SB27 could reduce the prevalence of antimicrobial-resistant on meat produced in California. We aimed to assess whether the implementation of SB27 was associated with significant decreases in resistance to medically important antimicrobials among strains contaminating raw chicken produced in California. We purchased raw chicken products in Southern California, including those produced in and outside of California, from 2017 to 2021 and cultured them for . Susceptibility to 19 antimicrobials was determined using the disk diffusion method. Changes in antimicrobial susceptibility over the course of the study were evaluated using the Mann-Kendall test. We observed significant decreases in resistance to multiple classes of antimicrobials in isolated from retail chicken meat from 2017 to 2021. Resistance to penicillins had a relative decrease of 14-18% annually in E. coli from chicken raised in California but not from chicken raised outside California, potentially indicating that SB27 was effective. Resistance to multiple other classes of antimicrobials saw an absolute decrease of up to 8% in chicken produced both inside and outside California. Our findings suggest that the downward trends in antimicrobial resistance among E. coli populations from California-produced chicken products reflect national trends. It is possible that the California SB27 legislation helped motivate industry-wide decreases in antimicrobial use among broiler chicken producers. Alternatively, the changes observed in California may have been driven by industry-wide trends independent of SB27. The lack of publicly available data regarding actual antimicrobial use in California and non-California broiler chicken production limits our ability to make stronger conclusions about our observations. https://doi.org/10.1289/EHP16115.