Bacterial cell-surface proteins play integral roles in host-pathogen interactions. These proteins are often architecturally and functionally sophisticated and yet few studies of such proteins involved in host-pathogen interactions have defined the domains or modules required for specific functions. Streptococcus pneumoniae (pneumococcus), an opportunistic pathogen that is a leading cause of community acquired pneumonia, otitis media and bacteremia, is decorated with many complex surface proteins. These include β-galactosidase BgaA, which is specific for terminal galactose residues β-1–4 linked to glucose or N-acetylglucosamine and known to play a role in pneumococcal growth, resistance to opsonophagocytic killing, and adherence. This study defines the domains and modules of BgaA that are required for these distinct contributions to pneumococcal pathogenesis. Inhibitors of β-galactosidase activity reduced pneumococcal growth and increased opsonophagocytic killing in a BgaA dependent manner, indicating these functions require BgaA enzymatic activity. In contrast, inhibitors increased pneumococcal adherence suggesting that BgaA bound a substrate of the enzyme through a distinct module or domain. Extensive biochemical, structural and cell based studies revealed two newly identified non-enzymatic carbohydrate-binding modules (CBMs) mediate adherence to the host cell surface displayed lactose or N-acetyllactosamine. This finding is important to pneumococcal biology as it is the first adhesin-carbohydrate receptor pair identified, supporting the widely held belief that initial pneumococcal attachment is to a glycoconjugate. Perhaps more importantly, this is the first demonstration that a CBM within a carbohydrate-active enzyme can mediate adherence to host cells and thus this study identifies a new class of carbohydrate-binding adhesins and extends the paradigm of CBM function. As other bacterial species express surface-associated carbohydrate-active enzymes containing CBMs these findings have broad implications for bacterial adherence. Together, these data illustrate that comprehending the architectural sophistication of surface-attached proteins can increase our understanding of the different mechanisms by which these proteins can contribute to bacterial pathogenesis.

Across six studies ( N = 904), we suggest a novel mechanism for race disparities in pain treatment: Perceiver deficits in discriminating real from fake pain for Black (relative to White) individuals. Across Studies 1–4, White participants (Studies 1–4) and Black participants (Study 2) were better at discerning authentic from inauthentic pain expressions for White targets than for Black targets. This effect emerged for both subtle (Studies 1 and 2) and intense (Studies 3 and 4) pain stimuli. Studies 5 and 6 examined consequences for medical care decisions by examining pain treatment recommendations by laypeople (Study 5) and pain authenticity judgments by medical providers (Study 6). This work advances theory in pain perception, emotion judgment, and intergroup relations. It also has practical significance for identifying unexplored mechanisms causing racial disparities in medical care.

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In 2017 alone, 783 000 children aged 12-17 years misused opioids with 14 000 using heroin. Opioid misuse and opioid use disorder (OUD) in adolescents and young adults are significant barriers to ending the HIV epidemic. To address these synergistic scourges requires dedicated practitioners and improved access to life-saving evidence-based treatment. Adolescents and young adults make up over one in five new HIV diagnoses even though they are less likely to be tested or know they are infected. Adolescents and young adults living with HIV are less likely to be retained in care or achieve virological suppression. OUD further leads to increased rates of risky behaviours (like sex without condoms), deceased retention in HIV care and decreased rates of viral suppression in this vulnerable population. Medications for opioid use disorder (MOUD) are recommended for adolescents and young adults with severe OUD and help retain youth in HIV treatment and decrease risk of death. However, due to stigma and lack of experience prescribing MOUD in adolescents, MOUD is often perceived as a last line option. MOUD remains difficult to access for adolescents with a shortage of providers and decreased options for treatment as compared to adults. Addiction treatment is infection prevention, and integrated addiction and HIV services are recommended to improve health outcomes. A multipronged approach including patient education, provider training and policy changes to improve access to treatment and harm reduction are urgently needed confront the drug use epidemic in youth.